当前期刊: Clinical Immunology Go to current issue    加入关注   
显示样式:        排序: 导出
我的关注
我的收藏
您暂时未登录!
登录
  • Impairment of agonist-induced M2 muscarinic receptor activation by autoantibodies from chagasic patients with cardiovascular dysautonomia
    Clin. Immunol. (IF 3.548) Pub Date : 2020-01-16
    Sabrina P. Beltrame; Laura C. Carrera Páez; Sergio R. Auger; Ahmad H. Sabra; Claudio R. Bilder; Claudia I. Waldner; Juan C. Goin
    更新日期:2020-01-16
  • Baseline derived neutrophil-to-lymphocyte ratio as a prognostic biomarker for non-colorectal gastrointestinal cancer patients treated with immune checkpoint blockade
    Clin. Immunol. (IF 3.548) Pub Date : 2020-01-15
    Shuang Li; Jianling Zou; Chang Liu; Xi Jiao; Jifang Gong; Jian Li; Zhenghang Wang; Ming Lu; Zhihao Lu; Lin Shen

    Background Biomarkers in non-colorectal gastrointestinal (GI) cancer patients receiving immune checkpoint blockades (ICBs) are still limited. Methods Data were prospectively collected from a discovery cohort (n = 53) and a validation cohort (n = 107) in patients with non-colorectal GI cancer receiving ICB, as well as a chemotherapy-only cohort (n = 171). System inflammatory markers and derived neutrophil-to-lymphocyte ratio (dNLR) were determined as biomarkers by univariate and multivariate analyses. Results A higher level of dNLR (cutoff = 3) was associated with shorter overall survival (OS) in discovery and validation cohorts. In pooled cohort, disease control rate (DCR) (28% vs. 48.1%) was associated with dNLR (p = .017). In univariate analysis, original tumor site, tumor histopathology, number of metastases, and dNLR were correlated with OS. In multivariate analysis, higher dNLR level was correlated with reduced OS (10.43 months vs. 4.20 months, p < .001). In chemotherapy-only cohort, dNLR was also correlated with DCR and OS. Conclusion Higher dNLR level was correlated with worse outcomes, suggesting that dNLR may help risk-group stratification and assist disease management strategies as a prognostic biomarker for non-colorectal GI patients receiving ICB.

    更新日期:2020-01-15
  • The increased IL-17-producing γδT cells promote tumor cell proliferation and migration in neuroblastoma
    Clin. Immunol. (IF 3.548) Pub Date : 2020-01-10
    Hui Zhang; Wenjia Chai; Wei Yang; Wei Han; Wenjun Mou; Yue Xi; Xi Chen; Hui Wang; Wei Wang; Hong Qin; Huanmin Wang; Xiaoli Ma; Xiaolin Wang; Jingang Gui

    Neuroblastoma (NB) is the most common solid extracranial malignancy in children with a considerable chance of metastatic progression. Prevalent evidence supports the anti-tumor role of γδT cells and these cells have been testing in clinical trials for constraining tumor growth. A small subpopulation of γδT cells releasing IL-17, however, were demonstrated to exert tumor-promoting effects in many aspects. In this study, we found an augment of IL-17+ γδT cells both in in vitro PAM-stimulated γδT-cell expanding culture and circulating γδT cells in NB patients. These patient-origin cells expanded in vitro by PAM in the presence of IL-17 polarizing condition were shown to promote the proliferation and migration of NB cells. Furthermore, an intrinsic preference for IL-17 polarization in NB γδT cells was revealed by mRNA microarray and Western Blot, which pointed to an up-regulated expression of multiple Th17-development related genes in addition to an increased phosphorylation level of STAT3.

    更新日期:2020-01-11
  • Longitudinal relationships between rheumatoid factor and cytokine expression by immunostimulated peripheral blood lymphocytes from patients with rheumatoid arthritis: New insights into B-cell activation
    Clin. Immunol. (IF 3.548) Pub Date : 2020-01-08
    John M. Davis; Cynthia S. Crowson; Keith L. Knutson; Sara J. Achenbach; Michael A. Strausbauch; Terry M. Therneau; Eric L. Matteson; Sherine E. Gabriel; Peter J. Wettstein

    To identify associations between immunostimulated cytokine production and disease characteristics, peripheral blood lymphocytes were collected from 155 adult patients with rheumatoid arthritis (RA) before and after a 5-year interval. The lymphocytes were activated in vitro with T-cell stimulants, cytosine-phosphate-guanine (CpG) oligonucleotide, and medium alone (negative control). Expression of 17 cytokines was evaluated with immunoassays, and factor analysis was used to reduce data complexity and identify cytokine combinations indicative of cell types preferentially activated by each immunostimulant. The findings showed that the highest numbers of correlations were between cytokine levels and rheumatoid factor (RF) positivity and between cytokine levels and disease duration. Scores for cytokines driven by CpG and medium alone were negatively associated with RF positivity and disease duration at baseline but positively associated with both at 5 years. Our findings suggest that RF expression sustained over time increases activation of B cells and monocytes without requirements for T-cell functions.

    更新日期:2020-01-09
  • Predictive value of mesangial C3 and C4d deposition in IgA nephropathy
    Clin. Immunol. (IF 3.548) Pub Date : 2019-12-31
    Ki Heon Nam; Young Su Joo; Changhyun Lee; Sangmi Lee; Joohwan Kim; Hae-Ryong Yun; Jung Tak Park; Tae Ik Chang; Dong-Ryeol Ryu; Tae-Hyun Yoo; Ho Jun Chin; Shin-Wook Kang; Hyeon Joo Jeong; Beom Jin Lim; Seung Hyeok Han

    We aimed to determine the relative contribution of each complement (C3 and C4d) deposition to the progression of IgA nephropathy (IgAN). We enrolled a total of 380 patients with biopsy-confirmed IgAN. Mesangial deposition of C3(<2+ vs. ≥2+) and C4d(positive vs. negative) was evaluated by immunofluorescence staining and immunohistochemistry, respectively. Study endpoint was the composite of a 30% decline in eGFR or ESRD. The risk of reaching the primary outcome was significantly higher in patients having C3 ≥ 2+ and C4d(+) than in corresponding counterparts. Adding C3 deposition to clinical data acquired at kidney biopsy modestly increased the area under the receiver-operating characteristic curve, net reclassification improvement, and integrated discrimination improvement (IDI); adding C4d increased IDI only. In conclusion, mesangial C3 and C4d deposition was an independent risk factor for progression of IgAN. C3 showed better predictability than C4d, suggesting that lectin pathway alone has limited clinical prognostic value.

    更新日期:2019-12-31
  • Eczematous dermatitis in primary immunodeficiencies: A review of cutaneous clues to diagnosis
    Clin. Immunol. (IF 3.548) Pub Date : 2019-12-30
    Sidney Hoskins; Suzanne Skoda-Smith; Troy R. Torgerson; Markus D. Boos

    Primary immunodeficiency Disorders (PIDD) are a varied group of heritable disorders characterized by defects in components of the innate and/or adaptive arms of the immune system. Although diagnosing these disorders is often challenging, the skin is a readily accessible and easily assessable organ that may provide clues to a diagnosis of PIDD. Specifically, many immunodeficiencies are associated with characteristic cutaneous eruptions that, based on their morphology, distribution and symptomatology, may suggest a specific underlying diagnosis. This review will discuss an approach to identifying and managing PIDDs that typically present with eczematous dermatitis.

    更新日期:2019-12-30
  • Pre-transplant assessment of pp65-specific CD4 T cell responses identifies CMV-seropositive patients treated with rATG at risk of late onset infection
    Clin. Immunol. (IF 3.548) Pub Date : 2019-12-28
    Maria O. López-Oliva; Virginia Martínez; Aranzazu Rodríguez-Sanz; Laura Álvarez; M. José Santana; Rafael Selgas; Carlos Jiménez; Teresa Bellón

    Assessment of CMV-specific T cell immunity might be a useful tool in predicting CMV infection after solid organ transplantation. We have investigated CD4 and CD8 T-cell responses to CMV pp65 and IE-1 antigens in a prospective study of 28 CMV-seropositive kidney transplant recipients who were administered lymphocyte-depleting antibodies (Thymoglobulin®) as induction treatment and with universal prophylaxis for CMV infection. The response was analyzed by intracellular flow cytometry analysis of IFN-γ production in pretransplant samples and at 1, 6, 12 and 24 months post-transplant.. Overall, only pretransplant CD4 T-cell responses to pp65 were significantly lower (p = .004) in patients with CMV replication post-transplant. ROC curve analysis showed that pre-transplant frequencies of pp65-specific CD4 + T cells below 0.10% could predict CMV infection with 75% sensitivity and 83.33% specificity (AUC: 0.847; 95% CI: 0.693–1.001; p = .0054) and seem to be mandatory for efficient control of CMV viral replication by the host immune system. In conclusion, the functional assessment of CMV-specific CD4 T-cell immunity pretransplant in seropositive patients may allow the identification of Thymoglobulin®-treated kidney transplant recipients at risk of developing CMV infection post-transplantation.

    更新日期:2019-12-29
  • A novel de novo NLRC4 mutation reinforces the likely pathogenicity of specific LRR domain mutation
    Clin. Immunol. (IF 3.548) Pub Date : 2019-12-20
    Chai Teng Chear; Revathy Nallusamy; Scott W. Canna; Kwai Cheng Chan; Mohd Farid Baharin; Munirah Hishamshah; Hamidah Ghani; Adiratna Mat Ripen; Saharuddin Bin Mohamad

    Autoinflammatory disorders are characterized by dysregulated innate immune response, resulting in recurrent uncontrolled systemic inflammation and fever. Gain-of-function mutations in NLRC4 have been described to cause a range of autoinflammatory disorders. We report a twelve-year-old Malay girl with recurrent fever, skin erythema, and inflammatory arthritis. Whole exome sequencing and subsequent bidirectional Sanger sequencing identified a heterozygous missense mutation in NLRC4 (NM_001199138: c.1970A > T). This variant was predicted to be damaging in silico, was absent in public and local databases and occurred in a highly conserved residue in the leucine-rich repeat (LRR) domain. Cytokine analysis showed extremely high serum IL-18 and IL-18/CXCL9 ratio, consistent with other NLRC4-MAS patients. In summary, we identified the first patient with a novel de novo heterozygous NLRC4 gene mutation contributing to autoinflammatory disease in Malaysia. Our findings reinforce the likely pathogenicity of specific LRR domain mutations in NLRC4 and expand the clinical spectrum of NLRC4 mutations.

    更新日期:2019-12-20
  • High-dose intravenous methylprednisolone in juvenile non-infectious uveitis: A retrospective analysis
    Clin. Immunol. (IF 3.548) Pub Date : 2019-12-18
    Anja Schnabel; Elisabeth Unger; Normi Brück; Reinhard Berner; Ursula Range; Annette Holl-Wieden; Henner Morbach; Anna Leszczynska; Viktoria Bau; Christian M. Hedrich

    Non-infectious uveitis is associated with visual impairment and blindness. Non-biologic treatment for non-infectious uveitis is not based on strong evidence. A retrospective chart review was conducted to investigate treatment response to high-dose intravenous methylprednisolone (IVMP) in children with non-infectious uveitis. Fifty-six patients (93 eyes affected) were included. In 29% uveitis was associated with juvenile idiopathic arthritis. Uveitis predominately affected the anterior segment, was bilateral and recurrent. Complications were common and included visual loss, synechiae, cataract and/or retinal lesions. Patients received up to 5 IVMP at monthly intervals. Visual acuity improved at 3 and 6 months. Anterior chamber cells, synechiae, keratic precipitates, papillary and/or macular edema improved at 3 months. Children treated with ≥3 IVMP (vs 1 IVMP) experienced trends towards fewer relapses, fewer cataracts and less frequently required treatment with biologic agents. High-dose IVMP induce rapid improvement in children with non-infectious uveitis. Prospective randomized trials are required to confirm results.

    更新日期:2019-12-19
  • Signal inhibitory receptor on leukocytes (SIRL)-1 and leukocyte- associated immunoglobulin-like receptor (LAIR)-1 regulate neutrophil function in infants
    Clin. Immunol. (IF 3.548) Pub Date : 2019-12-13
    Sjanna B. Besteman; Amie Callaghan; Marije P. Hennus; Geertje H.A. Westerlaken; Linde Meyaard; Louis L. Bont

    During severe respiratory syncytial virus (RSV) bronchiolitis there is a massive influx of activated neutrophils to the lungs. An exaggerated immune response contributes to lung damage and disease severity during RSV infection. We have previously shown that normal adult neutrophil function can be modulated by agonists of SIRL-1. Here we aimed to measure the potential of two immune checkpoints: SIRL-1 and LAIR-1, to regulate the function of fresh blood and sputum neutrophils from infants with and without severe RSV bronchiolitis. We show a modest inhibition of the oxidative burst through SIRL-1 and LAIR-1, in control and RSV-infected infants. In addition, SIRL-1 and LAIR-1 inhibited neutrophil extracellular traps (NET) formation by sputum neutrophils of RSV patients. Altogether our data show that inhibitory receptors LAIR-1 and SIRL-1 can be used to regulate neutrophil function.

    更新日期:2019-12-13
  • The immunologic features of patients with early-onset and polyautoimmunity
    Clin. Immunol. (IF 3.548) Pub Date : 2019-12-12
    Kacie J. Hoyt; Talal A. Chatila; Luigi D. Notarangelo; Melissa M. Hazen; Erin Janssen; Lauren A. Henderson

    Inflammatory conditions are increasingly described in patients with primary immunodeficiencies; however, little is known about the prevalence of immune defects in patients who present first with autoimmunity. We describe the immunologic features of children with early-onset/polyautoimmunity followed in the Multiple Autoimmunity and Immunodeficiency (MAID) Clinic, where patients are co-managed by rheumatologists and immunologists. The most common autoimmune manifestations were cytopenias, lymphoproliferation, and colitis. Recurrent infections were noted in 65% of patients. Abnormalities in lymphocyte subsets and immunoglobulins were common. A pathogenic variant was identified in 19% of patients, and 2 novel inherited disorders were discovered. Additionally, 42% of patients had treatment changes implemented in the MAID clinic. By evaluating this unique cohort of patients, we report on the immunologic underpinning of early-onset/polyautoimmunity. The high rate of genetic diagnoses and treatment interventions in this population highlights the value of collaboration between rheumatologists and immunologists in the care of these complex patients.

    更新日期:2019-12-13
  • Childhood GPA, EGPA, and MPA
    Clin. Immunol. (IF 3.548) Pub Date : 2019-12-11
    Mehul Jariwala, Ronald M. Laxer

    Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a term used to describe rare primary systemic vasculitides affecting small and medium-sized blood vessels. AAV diseases which include Granulomatosis with Polyangiitis (GPA), Eosinophilic Granulomatosis with Polyangiitis (EGPA), Microscopic Polyangiitis (MPA) and renal limited ANCA vasculitis. These multisystemic disorders involve upper and lower respiratory tract and kidneys associated with organ damage and long term sequelae. Newer understanding of pathogenesis in AAV have paved the way for clinical research with different biologic therapies. In spite of the paucity of clinical trials in pediatric AAV, the long-term survival of patients with AAV has improved dramatically. International collaborations will help to conduct clinical trials in pediatric AAV and help in better understanding of remission rates, relapse rates, and other outcomes. This article aims to provide a comprehensive review of pediatric AAV with a focus on epidemiology, disease pathogenesis, treatment trials, and prognosis.

    更新日期:2019-12-11
  • Juvenile idiopathic arthritis-associated uveitis
    Clin. Immunol. (IF 3.548) Pub Date : 2019-12-09
    Ethan S. Sen, A.V. Ramanan

    Juvenile idiopathic arthritis (JIA) is the commonest rheumatic disease in children and JIA-associated uveitis its most frequent extra-articular manifestation. The uveitis is potentially sight-threatening and so carries a considerable risk of morbidity. The commonest form of uveitis seen in JIA is chronic anterior uveitis which is almost always asymptomatic in the initial stages. Therefore, screening for JIA-associated uveitis in at-risk patients is essential. The aim of early detection and treatment is to minimise intra-ocular inflammation and avoid complications leading to visual loss, resulting from both disease activity and medications. There is increasing evidence for the early introduction of systemic immunosuppressive therapies in order to reduce topical and systemic glucocorticoid use. Two randomised controlled trials of adalimumab in JIA-associated uveitis provide convincing evidence for the use of this biologic in patients who fail to respond adequately to methotrexate. Tocilizumab and baricitinib are being investigated as alternatives to anti-tumour necrosis factor drugs.

    更新日期:2019-12-11
  • Morbidity in an adenosine deaminase-deficient patient during 27 years of enzyme replacement therapy
    Clin. Immunol. (IF 3.548) Pub Date : 2019-12-05
    Eyal Grunebaum, Brenda Reid, Ahmed Naqvi, Michael S. Hershfield, Vy Hong-Diep Kim, Matthew P. Muller, Lisa K. Hicks, Erika Lee, Stephen Betschel, Chaim M. Roifman

    Introduction Adenosine deaminase (ADA) deficiency causes severe immunodeficiency that is lethal in infancy. Enzyme replacement therapy (ERT) can improve the metabolic, immune and non-immune abnormalities in patients prior to transplantation, however, its benefits over extended periods are not well characterized. We describe a 28-year-old female who received ERT for 27 years. She suffered from EBV negative B cell lymphoma of the hip at 14 years of age and Guillian-Barre Syndrome 2 years later. At 22 years of age, she experienced a gastrointestinal infection with Mycobacterium genavense. At 26 years of age, lymphoma reoccurred with multiple liver lesions followed by Mycobacterium genavense infection with dissemination to the brain. Throughout this period, ADA activity in the plasma was within the therapeutic range. Repeated evaluations demonstrated very low lymphocyte counts and impaired T cell function. Conclusions ERT might be insufficient to maintain normal immunity over extended periods in some ADA-deficient patients.

    更新日期:2019-12-05
  • IL-6 is present in beta and alpha cells in human pancreatic islets: Expression is reduced in subjects with type 1 diabetes
    Clin. Immunol. (IF 3.548) Pub Date : 2019-12-03
    Sakthi Rajendran, Florence Anquetil, Estefania Quesada-Masachs, Madeleine Graef, Nathaly Gonzalez, Sara McArdle, Tiffany Chu, Lars Krogvold, Knut Dahl-Jørgensen, Matthias von Herrath

    IL-6 is a pro-inflammatory cytokine upregulated in some autoimmune diseases. The role of IL-6 in the development of type 1 diabetes (T1D) is unclear. Clinical studies are investigating whether tocilizumab (anti-IL-6 receptor) can help preserve beta cell function in patients recently diagnosed with T1D. However, in some rodent models and isolated human islets, IL-6 has been found to have a protective role for beta cells by reducing oxidative stress. Hence, we systematically investigated local tissue expression of IL-6 in human pancreas from non-diabetic, auto-antibody positive donors and donors with T1D and T2D. IL-6 was constitutively expressed by beta and alpha cells regardless of the disease state. However, expression of IL-6 was highly reduced in insulin-deficient islets of donors with T1D, and the expression was then mostly restricted to alpha cells. Our findings suggest that the implication of IL-6 in T1D pathogenesis might be more complex than previously assumed.

    更新日期:2019-12-04
  • Reduced PD-1 expression on circulating CXCR5+ and CXCR5− FOXP3+ Treg cells marks type 1 diabetes initiation in children
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-30
    Andrea Vecchione, Jolanda Gerosa, Roberta Di Fonte, Tatiana Jofra, Cicalese Maria Pia, Vincenzo Napoleone, Elio Ippolito, Giuseppe Galvani, Francesca Ragogna, Angela Stabilini, Eleonora Bianconi, Pauline Grogan, Clara Bonura, Riccardo Bonfanti, Giulio Frontino, Rita Nano, Raffaela Melzi, Maurizio De Pellegrin, Georgia Fousteri

    Autoantibodies (AAbs) are a hallmark of Type 1 diabetes (T1D). Alterations in the frequency and phenotype of follicular helper (Tfh) T cells have been previously documented in patients with type 1 diabetes (T1D), but the contribution of follicular Treg cells, which are responsible for suppressing AAb development, is less clear. Here, we investigated the frequency and activation status of follicular (CXCR5+) and CXCR5− Treg cells in the blood of children with new onset T1D and children with risk for developing T1D (AAb-positive) and compared them to AAb-negative controls. Blood CXCR5+ and CXCR5− Treg cells were higher in frequency children with new onset T1D and expressed reduced amounts of PD-1 as compared to controls. Interestingly, the proportion of circulating FOXP3+ Tregs expressing PD-1 was also reduced in AAb-positive at-risk children as compared to controls, suggesting its potential use as a biomarker of disease initiation.

    更新日期:2019-11-30
  • Emerging molecular biomarkers for predicting therapy response in psoriatic arthritis: A review of literature
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-27
    Juliëtte Pouw, Emmerik Leijten, Timothy Radstake, Marianne Boes

    Psoriatic arthritis (PsA) is a heterogeneous, chronic inflammatory musculoskeletal disorder that affects ~0.1% of the population. PsA may severely impact quality-of-life and constitutes a significant economic burden on our health care system. While early effective treatment is deemed essential to prevent irreversible joint damage and functional impairment, not all patients respond to the same disease modifying anti-rheumatic drugs (DMARDs). DMARD options for PsA are rapidly evolving, yet only 50–60% of patients show a satisfactory response to their first-line DMARD therapy. Hence, there is an urgent medical need to predict which patients benefit from a particular treatment. To this end, molecular biomarkers capable of predicting therapeutic response are currently being scrutinized in clinical studies, that together should build a framework for clinical guidelines that improve personalized targeted treatment. In this review new developments within the field of biomarker discovery for predicting therapeutic response to DMARDs in PsA are examined.

    更新日期:2019-11-28
  • Occurrence of major anti-retinal autoantibodies associated with paraneoplastic autoimmune retinopathy
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-23
    Grazyna Adamus, Rachel Champaigne, Sufang Yang

    Autoantibodies (AAbs) against retinal antigens can be found in patients with cancer and unexplained vision loss unrelated to the cancer metastasis. Cancer-associated retinopathy (CAR) is a rare paraneoplastic visual syndrome mediated by AAbs. Our goal was to determine whether CAR patients with different malignancies have a specific AAb or repertoire of AAbs that could serve as biomarkers for retinal disease. We found AAbs against 12 confirmed retinal antigens, with α-enolase being the most frequently recognized. The significant finding of the study was a high incidence of anti-aldolase AAbs in colon-CAR, anti-CAII in prostate-CAR, and anti-arrestin in skin melanoma patients thus these AAbs could serve as biomarkers in the context of clinical presentation and could support the diagnosis of CAR. However, a lack of AAb restriction to any one antigenic protein or to one retinal cellular location makes screening for a CAR biomarker challenging.

    更新日期:2019-11-26
  • Distinct molecular response patterns of activating STAT3 mutations associate with penetrance of lymphoproliferation and autoimmunity
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-23
    Sabine Jägle, Maximilian Heeg, Sarah Grün, Anne Rensing-Ehl, Maria Elena Maccari, Christian Klemann, Neil Jones, Kai Lehmberg, Claudia Bettoni, Klaus Warnatz, Bodo Grimbacher, Ariane Biebl, Uwe Schauer, Rosie Hague, Olaf Neth, Andrea Mauracher, Jana Pachlopnik Schmid, Alexandre Fabre, Stephan Ehl

    Germline STAT3 gain-of-function (GOF) mutations have been linked to poly-autoimmunity and lymphoproliferation with variable expressivity and incomplete penetrance. Here we studied the impact of 17 different STAT3 GOF mutations on the canonical STAT3 signaling pathway and correlated the molecular results with clinical manifestations. The mutations clustered in three groups. Group 1 mutants showed altered STAT3 phosphorylation kinetics and strong basal transcriptional activity. They were associated with the highest penetrance of lymphoproliferation and autoimmunity. Group 2 mutants showed a strongly inducible transcriptional reporter activity and were clinically less penetrant. Group 3 mutants were mostly located in the DNA binding domain and showed the strongest DNA binding affinity despite a poor transcriptional reporter response. Thus, the GOF effect of STAT3 mutations is determined by a heterogeneous response pattern at the molecular level. The correlation of response pattern and clinical penetrance indicates a significant contribution of mutation-determined effects on disease manifestations.

    更新日期:2019-11-26
  • T-cell activation and cardiovascular risk in adults with type 2 diabetes mellitus: A systematic review and meta-analysis
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-22
    Tawanda Maurice Nyambuya, Phiwayinkosi Vusi Dludla, Vuyolwethu Mxinwa, Bongani Brian Nkambule

    Background Chronic immune activation has been described in the development of cardiovascular diseases (CVDs) and in the pathogenesis of type 2 diabetes mellitus (T2D). However, the precise functional role of T-cells remains controversial. We therefore, assessed T-cell activation and cardiovascular risk in T2D. Methods The protocol was registered with PROSPERO [CRD42018099745]. We searched electronic databases and grey literature for eligible studies. The risk of bias and quality of evidence were assessed and the random-effects model was used in the meta-analysis. Findings Fifteen studies met the inclusion criteria. We report on increased T-cell activation in T2D and nondiabetics with CVD. Comorbidity of T2D and CVD (T2D + CVD) exacerbated T-cell activation. In addition, T2D + CVD comorbidity was associated with an increased CVD risk profile. Conclusion This meta-analysis suggests increased T-cell activation in T2D and nondiabetics with CVD. Moreover, an increased cardiovascular risk in patients with T2D which is exacerbated in T2D and CVD comorbidity.

    更新日期:2019-11-22
  • Linking genetic variation with epigenetic profiles in Sjögren's syndrome
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-22
    Pinelopi Arvaniti, Christelle Le Dantec, Amandine Charras, Marina A. Arleevskaya, Christian M. Hedrich, Kalliopi Zachou, George N. Dalekos, Yves Renaudineau

    DNA methylation represents an important regulatory event governing gene expression that is dysregulated in Sjögren's syndrome (SjS) and a number of autoimmune/inflammatory diseases. As disease-associated single-nucleotide polymorphisms (SNPs) have relevance in controlling DNA methylation, 94 non-HLA SjS-SNPs were investigated, among them 57 (60.6%) with widespread effects on 197 individual DNA methylation quantitative trait loci (meQTL) were selected. Typically, these SNPs are intronic, possess an active promoter histone mark, and control cis-meQTLs located around transcription start sites. Interplay is independent of the physical distance between SNPs and meQTLs. Using epigenome-wide association study datasets, SjS-meQTLs were characterized (41 genes and 13 DNA methylation CpG motifs) and for the most part map to a pro-inflammatory cytokine pathway, which is important for the control of DNA methylation in autoimmune diseases. In conclusion, exploring meQTLs represents a valuable tool to predict and investigate downstream effects of genetic factors in complex diseases such as SjS.

    更新日期:2019-11-22
  • Dysregulated actin dynamics in activated PI3Kδ syndrome
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-21
    Jacqueline G. Wallace, Pedro Zambrano-Rodas, Wilmer Córdova-Calderón, Santiago Estrada-Turriate, Daniel Mendoza-Quispe, Yesenia Limache Ontiveros, Raif S. Geha, Janet Chou, Craig D. Platt

    Activated PI3Kδ syndrome (APDS) Type I results from gain-of-function mutations in PIK3CD, which encodes the p110δ subunit of PI3Kδ. Abnormal actin dynamics have been hypothesized to contribute to the lymphopenia associated with this disease but have not been studied in patients with APDS. We report a patient with APDS who had widespread necrotic skin lesions that were responsive specifically to immunosuppressive therapy. EBV-transformed lymphoblastoid cells (EBV-LCLs) from patients with APDS exhibit increased polymerized actin and increased apoptosis, suggesting a contribution of impaired actin dynamics to this disease.

    更新日期:2019-11-22
  • Towards standardization of immune functional assays
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-21
    William Mouton, Chloé Albert Vega, Mathilde Boccard, François Bartolo, Guy Oriol, Jonathan Lopez, Alexandre Pachot, Julien Textoris, François Mallet, Karen Brengel-Pesce, Sophie Trouillet-Assant

    Recent advances in the immunotherapy field require evaluation of the immune function to adapt therapeutic decisions. Immune functional assays (IFA) are able to reveal the immune status and would be useful to further adapt/improve patient's care. However, standardized methods are needed to implement IFA in clinical settings. We carried out an independent validation of a published method used to characterize the underlying host response to infectious conditions using an IFA. We evaluate the reproducibility and robustness of this IFA and associated readout using an independent healthy volunteers (HV) cohort. Expression of a 44 genes-signatures and IFNγ protein secretion and gene-expression was assessed after stimulation. We observed a strong host-response correlation between the two cohorts. We also highlight that standardized methods for immune function evaluation exist and could be implemented in larger-scale studies. This IFA could be a relevant tool to reveal innate/adaptive immune dysfunction in immune-related disorders patients.

    更新日期:2019-11-22
  • Evaluation of polysaccharide typhim vi antibody response as a predictor of humoral immunodeficiency in haematological malignancies
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-21
    J. Ochoa -Grullón, C. Benavente Cuesta, C. Pérez López, A. Peña Cortijo, A. Rodríguez de la Peña, A. Álvarez Carmona, M. Mateo Morales, K. Llano -Hernández, L.J. Williams, E. Rodríguez de Frías, K. Guevara -Hoyer, G. Cordero Torres, C. Orte, M. Fernández -Arquero, L. Fernández -Paredes, I. Serrano -García, M.J. Recio, R. Pérez de Diego, S. Sánchez -Ramón

    An increasing healthcare challenge in the management of haematological malignancy (HM) is secondary immunodeficiency. From January 2019, the EMA included the evaluation of specific antibody (Ab) responses to better select patients for IgRT. We evaluated Ab responses to pneumococcal and Salmonella typhi pure polysaccharide immunization in a cohort of 42 HM patients and 24 healthy-controls. Pre-post specific Ab concentrations were measured by ELISA at 4 weeks. Globally, significantly lower TV seroprevalence (9%) compared to PPV (76%) (p < .001) was observed. TV non responders (88%) were higher than PPV non responders (62%) (p < .0001) and correlated better to infectious history. By ROC analysis, pre-post 5-fold TV increase was the best cut-off to discriminate HM with recurrent infections and controls (sensitivity 91%, specificity 100%). Despite the small sample cohort, our results suggest that specific anti-S typhi Ab response is a useful complementary assay in the diagnosis and management decision of SID to HM.

    更新日期:2019-11-21
  • Clinicopathological characteristics of dysplastic teratomous neuroglia with anti-N-methyl-d-aspartate receptor encephalitis
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-19
    Yangyang Xiao, Jian Li, Lingjuan Liu, Jie Xiong, Jie Xu, Qingchun Liang, Xiaoling She, Hong Tan, Yong Ma, Ding’an Mao, Liqun Liu

    In this study, we investigated whether unique pathological characteristics exist in teratomas that can trigger autoimmune anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. We compared a case of retroperitoneal teratoma associated with anti-NMDAR encephalitis and four control cases. The encephalitis-positive case showed that (i) more dysplastic neuroglia with higher Ki-67 labeling index values than the control cases, which met the diagnostic criteria of astrocytoma, (ii) the NMDAR subunit NR1 was expressed more abundantly in neuroglial tissue where many neuroglial cells co-expressed glial fibrillary acidic protein (GFAP) and NR1 and formed abnormally large cellular masses, (iii) intense NR1 expression occurs in squamous epithelium near neuroglial tissue and lymphocyte infiltration. This study showed that dysplastic neuroglial tissue resembling central nervous system tumors, which might promote autoimmunity, distinguished the case with NMDAR encephalitis from the controls. Additionally, abnormal expression of NR1 occurs in non-neural tissues and could be triggered by inflammation and participate in autoimmunity.

    更新日期:2019-11-19
  • NFKB2 regulates human Tfh and Tfr pool formation and germinal center potential
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-18
    Pasqualina De Leo, Luisa Gazzurelli, Manuela Baronio, Davide Montin, Silvia Di Cesare, Carmen Giancotta, Francesco Licciardi, Caterina Cancrini, Alessandro Aiuti, Alessandro Plebani, Maria Pia Cicalese, Vassilios Lougaris, Georgia Fousteri
    更新日期:2019-11-18
  • Immunological effects of sublingual immunotherapy with Japanese cedar pollen extract in patients with combined Japanese cedar and Japanese cypress pollinosis
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-16
    Hirotaka Kikuoka, Hideaki Kouzaki, Koji Matsumoto, Hiroyuki Arai, Sayuri Yamamoto, Ichiro Tojima, Shino Shimizu, Hiromi Miyashita, Yukiko Ogawa, Toshihiro Osada, Mitsuhiro Okano, Atsushi Yuta, Takeshi Shimizu

    Sublingual immunotherapy (SLIT) with Japanese cedar (JCe) pollinosis was expected to be effective for Japanese cypress (JCy) pollinosis. However, only a half of JCy pollinosis patients clinically improved. Therefore, we examined the immunological effect of SLIT for JCy pollinosis. Peripheral blood mononuclear cells (PBMCs) from patients with JCe and JCy pollinosis who did and did not receive SLIT were incubated with Cry j 1, Cha o 1 and Cha o 3 antigens. Basophil activation test (BAT) were performed. Production of IL-5 and IL-17 induced by antigens was inhibited in the SLIT group. Cry j 1-specific production of IL-10 was increased, and serum Cry j 1-specific IgE and -IgG4 were elevated. However, Cha o 1- or Cha o 3-specific production of IL-10 and specific IgG4 was not increased. Antigens-specific BAT did not decrease after SLIT. New SLIT with JCe and JCy is needed for patients with combined JCe and JCy pollinosis.

    更新日期:2019-11-18
  • The helminth-derived peptide GK-1 induces an anti-tumoral CD8 T cell response associated with downregulation of the PD-1/PD-L1 pathway
    Clin. Immunol. (IF 3.548) Pub Date : 2019-07-09
    Noé Rodríguez-Rodríguez, Iris K. Madera-Salcedo, Emmanuel Bugarin-Estrada, Elizabeth Sánchez-Miranda, Diana Torres-García, Jacquelynne Cervantes-Torres, Gladis Fragoso, Florencia Rosetti, José C. Crispín, Edda Sciutto

    CD8 T cells can kill malignant cells in an antigen-specific manner. However, anti-tumoral responses are usually limited by suppressive factors that curb the effector responses of tumor-infiltrating CD8 T cells. Therapeutic strategies to overcome intra-tumoral T cell suppression, for example immune checkpoint inhibition, have been clinically effective in patients with cancer. Here, we provide data that demonstrates that GK-1, a peptide derived from the parasite Taenia crassiceps, promotes an anti-melanoma CD8 T cell response with heightened effector characteristics that leads to an increased amount of tumor-infiltrating CD44+ IFN-γ-producing CD8 T cells. The response induced by GK-1 was associated with a reduction in the expression of PD-1 and PD-L1 on tumor-infiltrating CD8 and dendritic cells, respectively, effects that led to a dramatic decrease in tumor burden. Our results suggest that the immunomodulatory properties of GK-1 may promote a CD8 T cell response that may be therapeutically useful in the setting of cancer.

    更新日期:2019-11-18
  • Cellular immune responses against natural human papillomavirus infections among men in Kisumu, Kenya
    Clin. Immunol. (IF 3.548) Pub Date : 2019-05-02
    R.O. Ondondo, E.A. Bukusi, Z.W. Ng'ang'a, M. Kiptoo, S. Mpoke

    Human papillomavirus (HPV) is associated with ano-genital and cervical cancer. Persistence of oncogenic HPV genotypes is a requirement for development and progression of malignancies. Although, >70% of women clear incident HPV infections, data on natural history and HPV immunology among men is limited. To evaluate cell-mediated immune responses to natural HPV infections among men, we assessed cytokine responses on PBMCs collected from men with persistent or cleared HPV. Men with HPV clearance and those with HPV persistence had increased odds (6-times and 3-times respectively) of mounting cytokine responses compared to HPV uninfected men. Th1 cytokines IFN-γ (5.1-fold) and IL-2 (4.2-fold) were significantly (p < 0.0001) upregulated among men with HPV clearance compared to HPV uninfected men. Among men with HPV clearance compared to those with persistent HPV infection, only IFN-γ (2.4–fold) and IL-2 (3.0–fold) were significantly (p < 0.0001) upregulated. Th1 cell-mediated cytokine response was associated with natural HPV clearance in men.

    更新日期:2019-11-18
  • T cell receptor revision and immune repertoire changes in autoimmune diseases
    Clin. Immunol. (IF 3.548) Pub Date : 2018-12-10
    Xi Jia, Bing Wang, Tianyu Zhai, Qiuming Yao, Qian Li, Jin-an Zhang

    Autoimmune disease (AID) is a condition in which the immune system breaks down and starts to attack the body. Some common AIDs include rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus and so forth. The changes in T-cell receptor (TCR) repertoire have been found in several autoimmune diseases, and may be responsible for the breakdown of peripheral immune tolerance. In this review, we discussed the processes of TCR revision in peripheral immune environment, the changes in TCR repertoire that occurred in various AIDs, and the specifically expanded T cell clones. We hope our discussion can provide insights for the future studies, helping with the discovery of disease biomarkers and expanding the strategies of immune-targeted therapy.

    更新日期:2019-11-18
  • Elevated levels of circulating invariant natural killer cell subsets are skewed toward Th2-like phenotype in children with sickle cell disease
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-11
    Mohamed-Rachid Boulassel, Abeer Al-Zubaidi, Shoaib Al-Zadjali, Zahra Al-Qarni, Nidaa Al-Naamany, Ahmed Al-Yarabi, Mohamed Elshinawy, Yasser Wali

    Invariant natural killer T (iNKT) cells are being considered as potential targets for immunotherapeutic strategies in a variety of conditions including sickle cell disease (SCD). However, relatively little is known about the fate of iNKT cell subsets in children with SCD. Herein, quantitative and qualitative analyses of circulating iNKT cell subsets were carried out in 120 children in steady state and 30 healthy controls. Children with SCD displayed significantly elevated levels of circulating iNKT cell subsets with a preferential polarization toward Th2-like cells. The known SCD modifiers did not influence levels of iNKT cell subsets, except that children carrying the Bantu haplotype exhibited elevated levels of CD4iNKT cells, and to lesser degree CD8iNKT cells. Collectively, these findings indicate that circulating iNKT cell subsets are significantly increased in children with SCD, and highlight the existence of imbalanced production of cytokines toward Th2-like phenotype, which seems to be associated with genetic polymorphisms.

    更新日期:2019-11-13
  • JNK and phosphorylated Bcl-2 predict multiple sclerosis clinical activity and glatiramer acetate therapeutic response
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-05
    Freidrich Anselmo, Alexandru Tatomir, Dallas Boodhoo, Armugam P. Mekala, Vinh Nguyen, Violeta Rus, Horea Rus
    更新日期:2019-11-06
  • The STAT signaling profile at the single cell level reveals novel insights in the association of FOXP3+ T regulatory cells with recurrent spontaneous abortions before and after lymphocyte immunotherapy
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-02
    Eleftheria Lamprianidou, Michail Daniilidis, Chryssoula Kordella, Emmanouela Zoulia, Evangelia Nakou, Antonios Gerofotis, Vasilaki Athina, George Pantos, Ioannis Kotsianidis

    Foxp3+ T regulatory cell (Tregs) are central in the pathobiology of recurrent spontaneous abortions (RSA). Signal transducer and activator of transcription (STAT) proteins instruct Treg differentiation and polarization, but the STAT signaling architecture of Tregs in RSA and its modifications by lymphocyte immunotherapy (LIT) are yet unknown. By using single-cell phospho-specific flow cytometry we show that the STAT signaling biosignature of Tregs in women with RSA was characterized by marked downregulation of the IFNα/pSTAT1&5, IL-6/pSTAT1&3 and IL-2/pSTAT5 signaling nodes compared to age-matched fertile females.. LIT partially restored all of these signaling axes in Tregs only in women who achieved pregnancy after treatment. Both the pretreatment biosignature of Tregs and its modulations by LIT were associated with therapeutic success. We conclude that STAT signaling pathways in Tregs are actively involved in the pathophysiology of RSA and may serve as a predictive tool for selecting patients who may benefit from LIT.

    更新日期:2019-11-04
  • A novel NFKBIA variant substituting serine 36 of IκBα causes immunodeficiency with warts, bronchiectasis and juvenile rheumatoid arthritis in the absence of ectodermal dysplasia
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-01
    Georgios Sogkas, Ignatius R. Adriawan, Felix C. Ringshausen, Ulrich Baumann, Claudia Schröder, Christian Klemann, Sandra von Hardenberg, Gunnar Schmidt, Auber Bernd, Alexandra Jablonka, Diana Ernst, Reinhold E. Schmidt, Faranaz Atschekzei

    Genetic studies have led to identification of an increasing number of monogenic primary immunodeficiency disorders. Monoallelic pathogenic gain-of-function (GOF) variants in NFKBIA, the gene encoding IκBα, result in an immunodeficiency disorder, typically accompanied by anhidrotic ectodermal dysplasia (EDA). So far, 14 patients with immunodeficiency due to NFKBIA GOF mutations have been reported. In this study we report three patients from the same family with immunodeficiency, presenting with recurrent respiratory tract infections, bronchiectasis and viral skin conditions due to a novel pathogenic NFKBIA variant (c.106 T > G, p.Ser36Ala), which results in reduced IκBα degradation. Immunological investigations revealed inadequate antibody responses against vaccine antigens, despite hypergammaglobulinemia. Interestingly, none of the studied patients displayed features of EDA. Therefore, missense NFKBIA variants substituting serine 36 of IκBα, differ from the rest of pathogenic GOF NFKBIA variants in that they cause combined immunodeficiency, even in the absence of EDA.

    更新日期:2019-11-01
  • An update on genetic susceptibility in lupus nephritis
    Clin. Immunol. (IF 3.548) Pub Date : 2019-11-01
    Song Kangkang, Liu Lu, Zhang Xuejun, Chen Xiangmei

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multiple system involvement and positive serum autoantibodies. Lupus nephritis (LN) is the most common and serious complication of SLE, and it is the main cause of death in patients with SLE. Abnormalities in the immune system lead to LN and involve a variety of cells (T cells, B cells, macrophages, NK cells, etc.), cytokines (interleukin, tumor necrosis factor α, etc.) and their related pathways. Previous studies have shown that the interactions of genetic, epigenetic and environmental factors contribute to the pathogenesis and development of LN. In recent years, one genome-wide association study (GWAS) and a number of gene association studies have explored the susceptibility genes of LN, including immunization-, inflammation-, adhesion- and other pathway-related genes. These genes participate in or suggest the pathogenesis and progression of LN. In this review, we summarize the genetic susceptibility of LN and discuss the possible mechanism underlying the susceptibility genes of LN.

    更新日期:2019-11-01
  • Juvenile-onset systemic lupus erythematosus: Update on clinical presentation, pathophysiology and treatment options
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-31
    Eve Mary Dorothy Smith, Hanna Lythgoe, Angela Midgley, Michael William Beresford, Christian Michael Hedrich

    Juvenile-onset systemic lupus erythematosus (jSLE) accounts for up to 20% of all SLE patients. Key differences between juvenile- and adult-onset (aSLE) disease include higher disease activity, earlier development of damage, and increased use of immunosuppressive treatment in jSLE suggesting (at least partial) infectivity secondary to variable pathomechanisms. While the exact pathophysiology of jSLE remains unclear, genetic factors, immune complex deposition, complement activation, hormonal factors and immune cell dysregulation are involved to variable extents, promising future patient stratification based on immune phenotypes. Though less effective and potentially toxic, jSLE patients are treated based upon evidence from studies in aSLE cohorts. Here, age-specific clinical features of jSLE, underlying pathomechanisms, treatment options and disease outcomes will be addressed. Future directions to improve the care of jSLE patients, including implementation of the Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) recommendations, biomarkers, treat to target and personalized medicine approaches are discussed.

    更新日期:2019-11-01
  • Biological depletion of neutrophils attenuates pro-inflammatory markers and the development of the psoriatic phenotype in a murine model of psoriasis
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-31
    Annika Havnaer, Hiu H. Lee, Dylan J. Carmichael, Luis R. Martinez, George Han

    Although neutrophils are considered a histologic hallmark of psoriasis, their pathophysiologic role in psoriasis remains unclear. We characterized the effects of neutrophil depletion via injection of monoclonal antibody 1A8 on the development of imiquimod (IMQ)-induced psoriatic lesions in a murine model. Lesions were followed with photographs and histologic analysis, revealing reduced psoriasiform scale and epidermal hyperplasia in neutrophil-depleted. ELISA and flow cytometry were used to determine relative levels of cytokines and immune cells. Compared to controls, IMQ-treated neutropenic mice had significantly lower levels of macrophages in tissue samples (P < .05) and displayed significantly lower numbers of CD4+ T-cells (P < .05). Neutropenic animals exhibited lower levels of TNF-α, IFN-γ, and IL-1β than controls (P < .05). These results show that neutropenia reduces the development of psoriasiform skin lesions and substantially decreases infiltration of pro-inflammatory cytokines and immune cells to IMQ-induced cutaneous lesions, suggesting an active role of neutrophils in maintaining inflammation in psoriasis.

    更新日期:2019-11-01
  • Immunoglobulin A deficiency in children, an undervalued clinical issue
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-31
    M.H. (Mischa) Koenen, J.M. (Joris) van Montfrans, E.A.M. (Elisabeth) Sanders, D. (Debby) Bogaert, L.M. (Lilly) Verhagen

    Immunoglobulin A (IgA) is the principal antibody in secretions that bathe the gastrointestinal and respiratory mucosal surfaces and acts as an important first line of defense against invasion of pathogenic micro-organisms. The reported prevalence rate of complete IgA deficiency in healthy children ranges from 1:170 to 1:400, and as a solitary condition, it is often considered of limited clinical importance. However, patients with IgA deficiency can develop recurrent respiratory and gastrointestinal infections, as well as allergic and autoimmune diseases. In children referred for recurrent respiratory tract infections, the observed prevalence rate increases more than tenfold. This review discusses several aspects of IgA deficiency in children, including immunologic and microbiome changes in early childhood and the potential consequences of this condition in later life. It illustrates the importance of early identification of children with impaired IgA production who deserve appropriate clinical care and follow-up.

    更新日期:2019-11-01
  • Recombinant human granulocyte macrophage-colony stimulating factor expressed in yeast (sargramostim): A potential ally to combat serious infections
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-30
    Giovanni Damiani, Thomas S. McCormick, Luis O. Leal, Mahmoud A. Ghannoum

    Granulocyte-macrophage-colony stimulating factor (GM-CSF), can direct the activation, proliferation and differentiation of myeloid-derived cells. It is also responsible for maturation and function of professional antigen presenting cells thereby impacting adaptive immune responses, while assisting to maintain epithelial barrier function. GM-CSF in combination with other endogenous cytokines and secondary stimuli, such as tumor necrosis factor can modulate pro-inflammatory monocyte priming via chromatin remodeling and enhanced transcriptional responses, a concept termed “trained immunity”. An increase in the incidence of opportunistic fungal infections was recently reported in patients with hematological cancers receiving treatment with the BTK inhibitor, Ibrutinib. Tec Kinase BTK is known to influence the expression of GM-CSFRα and regulates downstream signaling pathways, suggesting a role for GM-CSF in maintenance of defense against fungal infections in immune competent hosts. Further examination of the potential mechanism(s) of action for naturally occurring GM-CSF and recombinant human GM-CSF (rhu-GM-CSF) expressed in yeast (sargramostim) are reviewed.

    更新日期:2019-11-01
  • Immunomodulatory receptors are differentially expressed in B and T cell subsets relevant to autoimmune disease
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-25
    Katherine A. Murphy, Kartik Bhamidiphati, Samuel J.S. Rubin, Lucas Kipp, William H. Robinson, Tobias V. Lanz

    Inhibitory cell-surface receptors on lymphocytes, often called immune checkpoints, are powerful targets for cancer therapy. Despite their direct involvement in autoimmune pathology, they are currently not exploited therapeutically for autoimmune diseases. Understanding the receptors' expression patterns in health and disease is essential for targeted drug design. Here, we designed three 23-colour flow cytometry panels for peripheral-blood T cells, including 15 lineage-defining markers and 21 immunomodulatory cell-surface receptors, and a 22-marker panel for B cells. Blood samples from healthy individuals, multiple sclerosis (MS), and lupus (SLE) patients were included in the study. Several receptors show differential expression on regulatory T cells (Treg) compared to T helper (Th) 1 and Th17 cells, and functional relevance of this difference could be shown for BTLA and CD5. Unbiased multiparametric analysis revealed a subset of activated CD8+ T cells and a subset of unswitched memory B cells that are diminished in MS and SLE, respectively.

    更新日期:2019-10-25
  • Antagonistic role of IL-1ß and NLRP3/IL-18 genetics in chronic HIV-1 infection
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-24
    Edione C. Reis, Vinicius N.C. Leal, Lais T. da Silva, Marilia M.L. dos Reis, Enrique R. Argañaraz, Telma M. Oshiro, Alessandra Pontillo

    Host genetics affects both susceptibility and progression of HIV-1 infection. NLRP3 inflammasome provides a first-line defense in viral infections, and, accordingly, gain-of-function variants in NLRP3 have been associated with protection against HIV-1. Despite antiretroviral treatment (ART), HIV+ patients continue to present systemic inflammation with a heterogeneous prognosis. As NLRP3 inflammasome is involved in several chronic diseases by amplifying “sterile” inflammation, its role in chronic phase of HIV infection has been postulated. Little is known about inflammasome genetics in HIV+ patients and whether it may play a role in the different clinical outcomes. Therefore, we questioned whether NLRP3 inflammasome genetics could affect the clinical course of HIV-1 infection as it does in host/virus interaction. For this purpose, we analyzed selected single nucleotide polymorphisms (SNPs) in ART-treated HIV+ patients (n = 300), in Long Term Non-Progressors/Elite Controllers and progressors (n = 133), and in HIV+ individuals submitted to dendritic cell (DC)-based immunotherapy (n = 19). SNPs leading to increased activation of NLRP3 inflammasome are beneficial for patients, while SNPs that negatively affect NLRP3 activation or IL-18 production, detrimental. In contrast, gain-of-function variant in IL1B is also detrimental for patients, suggesting that while IL-1ß possible contributes to immune exhaustion, the axis NLRP3-inflammasome/IL-18 could act positively in chronic infection. Functional assays supported genetic results: NLRP3 variants associated with good quality HIV+ DC, and IL1B -511C > T with a poor one. Loss-of-function SNPs affect HIV+ T cells proliferation. These findings proposed for the first time that NLRP3 inflammasome, mainly through IL-18, play a protective role in chronic HIV infection.

    更新日期:2019-10-25
  • Autoimmunity in women: An eXamination of eXisting models
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-24
    Grace J. Yuen

    In Western countries, about 5% of the population is affected by an autoimmune disease; in the United States, up to 23.5 million Americans suffer from autoimmune disorders [1]. Women comprise over 80% of the affected individuals for many autoimmune conditions, including Sjögren's syndrome, systemic sclerosis, Addison's disease, primary biliary cirrhosis, systemic lupus erythematosus (SLE), and autoimmune thyroid diseases like Grave's disease and Hashimoto's thyroiditis [2]. Additionally, the prevalence of rheumatoid arthritis, multiple sclerosis, and Sjögren's syndrome is also skewed towards women (3:1, 2:1, and 9:1, respectively) [3]. Though the reason for this sex-based disparity remains unknown, it has been speculated that sex hormone-dependent signaling, acting either in conjunction with or independently from sex-specific and X-linked gene expression, may modulate the immune system in women such that it predisposes them to autoimmunity [4]. Sex hormones clearly have a critical role in autoimmunity, as exemplified by the 15-fold reduction in risk of developing SLE in men compared to pre-menopausal women, though this risk drops by only 2-fold after menopause [5]. The focus of this brief review, however, will be to explore the potential link between X-chromosome inactivation, a critical biological event that occurs only in female cells, and the predisposition of women to autoimmunity.

    更新日期:2019-10-25
  • Adjuvant effect of TLR7 agonist adsorbed on aluminum hydroxide (AS37): A phase I randomized, dose escalation study of an AS37-adjuvanted meningococcal C conjugated vaccine
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-24
    Antonio Gonzalez-Lopez, Jaap Oostendorp, Thomas Koernicke, Tommaso Fadini, Ugo D'Oro, Sherryl Baker, Derek T. O’Hagan, Giuseppe Del Giudice, Emilio Siena, Oretta Finco, Duccio Medini

    An adjuvant system (AS37) has been developed containing a synthetic toll-like receptor agonist (TLR7a). We conducted a phase I randomized, observer-blind, dose-escalation study to assess the safety and immunogenicity of an investigational AS37-adjuvanted meningococcus C (MenC) conjugate vaccine in healthy adults (NCT02639351). A control group received a licensed MenC conjugate alum-adjuvanted vaccine. Eighty participants were randomized to receive one dose of control or investigational vaccine containing AS37 (TLR7a dose 12.5, 25, 50, 100 μg). All vaccines were well tolerated, apart from in the TLR7a 100 μg dose group, which had three reports (18.8%) of severe systemic adverse events. Four weeks after vaccination, human complement serum bactericidal assay seroresponse rates against MenC were 56–81% in all groups, and ELISA seroresponses were ≥81% for all AS37-adjuvanted vaccine groups (100% in 50 and 100 μg dose groups) and 88% in the control group. Antibody responses were maintained at six months after vaccination.

    更新日期:2019-10-25
  • A novel tool for clinical diagnosis of allergy operating a microfluidic immunoaffinity basophil activation test technique
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-24
    Zenib Aljadi, Frida Kalm, Caroline Nilsson, Ola Winqvist, Aman Russom, Joachim Lundahl, Anna Nopp

    The Basophil Activation Test (BAT) is a valuable allergy diagnostic tool but is time-consuming and requires skilled personnel and cumbersome processing, which has limited its clinical use. We therefore investigated if a microfluidic immunoaffinity BAT (miBAT) technique can be a reliable diagnostic method. Blood was collected from allergic patients and healthy controls. Basophils were challenged with negative control, positive control (anti-FcεRI), and two concentrations of a relevant and non-relevant allergen. CD 203 c and CD 63 expression was detected by fluorescent microscopy and flow cytometry. In basophils from allergic patients the CD 63% was significantly higher after allergen activation as compared to the negative control (p<.0001–p=.0004). Activation with non-relevant allergen showed equivalent CD 63% expression as the negative control. Further, the miBAT data were comparable to flow cytometry. Our results demonstrate the capacity of the miBAT technology to measure different degrees of basophil allergen activation by quantifying the CD 63% expression on captured basophils.

    更新日期:2019-10-25
  • 更新日期:2019-10-24
  • Independent association of low IFNλ1 gene expression and type I IFN score/IFNλ1 ratio with obstetric manifestations and triple antiphospholipid antibody positivity in primary antiphospholipid syndrome
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-19
    Christina-Maria Flessa, Stelios Vlachiotis, Adrianos Nezos, Evangelos Andreakos, Clio P. Mavragani, Maria G. Tektonidou

    Recent data suggest an important role of type I interferons (IFN) in antiphospholipid syndrome (APS). Here we aimed to evaluate the interplay of type I and type III (or IFNλs) IFNs in APS and potential clinical and serological associations. Our findings suggest that patients with primary APS (PAPS) and systemic lupus erythematosus (SLE)/APS displayed increased type I IFN scores but decreased IFNλ1 gene expression levels compared to healthy individuals, as assessed with real-time qPCR analysis in isolated peripheral blood mononuclear cells (PBMCs). Type I IFN score/IFNλ1 ratio was remarkably higher in patients with PAPS and SLE/APS as well as in SLE patients with or without antiphospholipid antibodies (aPL) vs controls. In conclusion, our results reveal an association between low IFNλ1 expression and obstetric APS. Moreover, the type I IFN score/IFNλ1 ratio seems to be a potential marker of high risk APS given its associations with triple aPL positivity.

    更新日期:2019-10-19
  • Reprograming of peripheral Foxp3+ regulatory T cell towards Th17-like cell in patients with active systemic lupus erythematosus
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-19
    Cen Jiang, Huaizhou Wang, Minghui Xue, Lin Lin, Jianbiao Wang, Gang Cai, Qian Shen

    Treg is essential to limit the extend and duration of the immune response, but its stability is still under debate. Here we demonstrate that IL-17-producing Treg cells (Th17-like cells) increased in peripheral blood of patients with Systemic Lupus Erythematosus (SLE). Notably, the Th17-like cells from patient with active SLE were characterized with some phenotype and function of Th17 cells. Upon stimulation, Helios-Foxp3 + CD4+ T cells decrease Foxp3 expression but increase expression of IL-17 and RORγt. Damage associated molecule pattern and inflammatory cytokines are important for induction of IL-17 expression in Treg cells. The Th17-like cells from patients with active SLE lose suppressive function and have robust response to stimulation of autoantigens. We also observed that the level of Th17-like cells in peripheral blood is closely associated with the clinical index of SLE. These findings suggest that instability of Treg plays a critical role in pathogenesis of autoimmune diseases.

    更新日期:2019-10-19
  • Screening of tumor-associated antigens based on Oncomine database and evaluation of diagnostic value of autoantibodies in lung cancer
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-17
    Tingting Wang, Hongchun Liu, Lu Pei, Kaijuan Wang, Chunhua Song, Peng Wang, Hua Ye, Jianying Zhang, Zhenyu Ji, Songyun Ouyang, Liping Dai

    Objectives The purpose of this study is to discover novel tumor-associated antigens (TAAs) to improve the diagnosis of lung cancer (LC). Materials and methods Oncomine database was used to discover potential TAAs from LC tissues, enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of autoantibodies against TAAs in two independent sets (identification set, n = 368; validation set, n = 1011). Results Analyses of sera from identification set showed that the sensitivity of autoantibodies against five TAAs (HMGB3, ZWINT, GREM1, NUSAP1 and MMP12) reached 57.1%, 42.4%, 38.0%, 36.4% and 20.7%, with area under ROC curve(AUC) of 0.85, 0.75, 0.71, 0.73 and 0.70, respectively. It also validated the diagnostic performances of these autoantibodies with AUC of 0.72, 0.65, 0.61, 0.64 and 0.64, respectively. Autoantibody against HMGB3 exhibited significantly increased frequency in early LC (53.3%) compared to advanced LC (29.3%) (P < .05). The positive rates of autoantibody against HMGB3 and NUSAP1 in serum of LC patients without distant metastasis were significantly higher than that of distant metastatic LC (P < .05). When each of the three protein biomarkers (CEA, CA125 and CYFRA21-1) was combined with anti-HMGB3 autoantibody, the sensitivity of early LC increased to 72.7%, 63.3% and 75.9% from 36.4%, 13.3% and 27.6%, respectively. Conclusion Autoantibodies against 5 TAAs (HMGB3, ZWINT, GREM1, NUSAP1 and MMP12) might have favorable diagnostic values in LC detection, and autoantibody against HMGB3 has the potential to serve as a serological biomarker in early-stage LC. The combination of protein biomarkers and anti-HMGB3 might contribute to detection of early-stage LC.

    更新日期:2019-10-17
  • Prognostic role of circulating neutrophil extracellular traps levels for long-term mortality in new end-stage renal disease patients
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-17
    Jwa-Kyung Kim, Hoi Woul Lee, Narae Joo, Hyung Seok Lee, Young Rim Song, Hyung Jik Kim, Sung Gyun Kim

    Dysregulation of innate immunity has been proposed as an important contributing factor for advanced atherosclerosis and resultant high mortality in hemodialysis (HD) patients. To evaluate the long-term prognostic role of in vivo neutrophil extracellular traps (NETs), we measured circulating serum nucleosome, myeloperoxidase (MPO), and DNase I levels in 281 incident HD patients. Circulating nucleosome level was significantly higher in HD patients compared to controls, and it was closely associated with MPO levels, suggesting increased in vivo NETs in uremia. Patients in the nucleosome Q4 group had significantly increased all-cause and adverse CV mortality compared to those in the Q1–3 group even after adjusting traditional risk factors Also, serum DNase I level was significantly higher in HD patients than controls (2.76 ± 1.02 ng/ml and 1.93 ± 0.85 ng/ml), but it had no correlation with NETs. Interestingly, it serves an additive biomarker for predicting poor CV outcomes. The two novel biomarkers might provide an importance independent prognostic significance in incident HD patients.

    更新日期:2019-10-17
  • Baricitinib experience on STING-associated vasculopathy with onset in infancy: A representative case from Turkey
    Clin. Immunol. (IF 3.548) Pub Date : 2019-10-15
    Sibel Balci, Rabia Miray Kisla Ekinci, Adriana Almeida de Jesus, Raphaela Goldbach-Mansky, Mustafa Yilmaz

    Stimulator of interferon genes associated vasculopathy with onset in infancy (SAVI), caused by heterozygote gain-of-function mutations in TMEM173, is characterized by fever attacks with ulcerating cutaneous manifestations on cold-sensitive areas and interstitial lung disease. A six-month-old boy was admitted to our hospital with fever, cough, and rash on the external surface of both upper and lower extremities. Respiratory symptoms consistent with ILD developed and skin lesions evolved to eschar formation particularly on acral regions. Ultimately, diagnosis of SAVI was confirmed at the age of 10 months due to the high level of interferon-score and a heterozygous N154S mutation in TMEM173. Since systemic corticosteroid and ruxolitinib were not effective, baricitinib was initiated at the age of 15 months, resulting in alleviation of fever attacks, cutaneous manifestations and respiratory symptoms within 2 months. In conclusion, we reported an infant diagnosed with SAVI at the age of 10 months and treated with baricitinib.

    更新日期:2019-10-16
  • Significance of peripheral mononuclear cells producing interferon-γ in response to insulin B:9–23-related peptides in subtypes of type 1 diabetes
    Clin. Immunol. (IF 3.548) Pub Date : 2019-09-13
    Yoichi Oikawa, Kumiko Sakamoto, Atsushi Satomura, Akifumi Haisa, Takeshi Katsuki, Yutaka Hattori, Ikuo Inoue, Mitsuhiko Noda, Akira Shimada

    Type 1 diabetes is largely caused by β-cell destruction through anti-islet autoimmunity. Reportedly, interferon (IFN)-γ-secreting peripheral blood mononuclear cells (PBMCs) specific to four insulin B-chain amino acid 9–23-related peptides (B:9–23rPep) were increased in type 1 diabetes participants. This study aimed to investigate the PBMC frequencies in subtypes of type 1 diabetes using enzyme-linked immunospot assay. In this cross-sectional study, peripheral blood samples were obtained from 148 participants including 72 with acute-onset type 1 diabetes (AT1D), 51 with slowly progressive insulin-dependent diabetes mellitus (SPIDDM), and 25 with type 2 diabetes. The frequency of B:9–23rPep-specific IFN-γ-producing PBMCs was significantly higher in AT1D participants than in SPIDDM and type 2 diabetes participants. Meanwhile, a significant inverse correlation was observed between the PMBC frequencies and insulin secretion capacity in SPIDDM participants. These findings suggest that the increased peripheral B:9–23rPep-specific IFN-γ immunoreactivity reflects decreased functional β-cell mass and greater disease activity of type 1 diabetes.

    更新日期:2019-09-14
  • Heparin and aspirin combination therapy restores T-cell phenotype in pregnant patients with antiphospholipid syndrome-related recurrent pregnancy loss
    Clin. Immunol. (IF 3.548) Pub Date : 2019-09-09
    Meiying Wang, Peng Zhang, Shengyan Yu, Gengmin Zhou, Jiyang Lv, Dhiraj Nallapothula, Chengshan Guo, Qingwen Wang, Ram Raj Singh

    Recurrent pregnancy loss (RPL) is the most common manifestation of anti-phospholipid syndrome (APS), and activated CD4+ T cells are involved in its pathogenesis. Treatment with low-molecular weight heparin (LMWH) and aspirin combination improves pregnancy outcome, however, its mechanism of action is unclear. We investigated the effect of this therapy on Th1/Th2 cells in 89 patients with APS-RPL. The results showed that serum cytokine levels, T cell phenotypes, and transcription factors' gene expression levels representing Th1 responses were higher, whereas those representing Th2 responses were lower in patients with APS-RPL at the time of early pregnancy. This Th1-bias was reversed in patients who had live birth after receiving the combination therapy at the time of delivery. Patients with miscarriages continued to exhibit Th1-bias. In conclusion, these data support a role of Th1-bias in the pathogenesis of APS-RPL and suggest restoring T-cell phenotype as a new immunomodulatory mechanism of LMWH/aspirin combination.

    更新日期:2019-09-10
  • Expression pattern of co-inhibitory molecules on CMV-specific T-cells in lung transplant patients
    Clin. Immunol. (IF 3.548) Pub Date : 2019-09-06
    Vasiliki Bessa, Ming Sun, Maike Meier, Ye Zeng, Shilei Xu, Sebastian Dolff, Urte Sommerwerck, Johannes Korth, Christian Taube, Clemens Aigner, Markus Kamler, Andreas Kribben, Monika Lindemann, Oliver Witzke, Benjamin Wilde

    Objectives Cytomegalovirus infection (CMVi) occurs frequently in transplant patients. Co-inhibitory molecules on CMV-specific T-cells (TCMV) in patients after lung transplantation were investigated. Methods 59 lung transplant patients were stratified according to anti-CMV serostatus at time of transplantation. The co-inhibitors Programmed-Death-Receptor-1 (PD1) and B-and-T-Lymphocyte-Attenuator (BTLA) were detected on TCMV by flow cytometry (FACS). Results TCMV were detectable in CMV sero-positive patients (R+) and in CMV sero-negative patients with a lung graft of a CMV sero-positive donor (D+/R−); in both cases, the frequency of TCMV was higher than in healthy controls (HC). PD-1 on TCMV was increased in D+/R+ and D+/R− patients as compared to HC. BTLA was significantly enhanced on TCMV of D+/R− patients vs. HC. R+ patients with CMV reactivation in the past had an increased fraction of BTLA+ TCMV. Conclusion In conclusion, the expression pattern of co-inhibitory molecules on TCMV is altered in patients after lung transplantation.

    更新日期:2019-09-06
  • A deep intronic mutation of c.1166-285 T > G in SLC46A1 is shared by four unrelated Japanese patients with hereditary folate malabsorption (HFM)
    Clin. Immunol. (IF 3.548) Pub Date : 2019-09-05
    Yusuke Tozawa, Shimaa Said Mohamed Ali Abdrabou, Natsuko Nogawa-Chida, Ritsuo Nishiuchi, Toshiaki Ishida, Yuichi Suzuki, Hideki Sano, Ryoji Kobayashi, Kenji Kishimoto, Osamu Ohara, Kohsuke Imai, Takuya Naruto, Kunihiko Kobayashi, Tadashi Ariga, Masafumi Yamada

    Hereditary folate malabsorption (HFM) is an autosomal recessive disease caused by mutations in SLC46A1 encoding the proton-coupled folate transporter (PCFT). HFM patients present with various clinical features including megaloblastic anemia, thrombocytopenia, combined immunodeficiency and neurodevelopmental disorders. In this study, we report the same deep intronic mutation of c.1166-285 T > G shared by four unrelated Japanese patients with HFM. This mutation was shown to generate a cryptic splice donor site for a 168-bp insertion of intron 3 sequences, leading to premature termination in the middle of this insertion. This mutation could be a founder mutation in the Japanese population, but also could be a hot-spot and could be present in undiagnosed HFM patients worldwide because of the difficulty to detect this mutation.

    更新日期:2019-09-06
  • Cytokine targets in lupus nephritis: Current and future prospects
    Clin. Immunol. (IF 3.548) Pub Date : 2018-09-02
    Christina Adamichou, Spyros Georgakis, George Bertsias

    Despite advancements in the care of lupus nephritis, a considerable proportion of patients may respond poorly or flare while on conventional immunosuppressive agents. Studies in murine and human lupus have illustrated a pathogenic role for several cytokines by enhancing T- and B-cell activation, autoantibodies production and affecting the function of kidney resident cells, therefore supporting their potential therapeutic targeting. To this end, there is limited post-hoc randomized evidence to suggest beneficial effect of belimumab, administered on top of standard-of-care, during maintenance therapy in lupus nephritis. Type I interferon receptor blockade has yielded promising results in preliminary SLE trials yet data on renal activity are unavailable. Conversely, targeting interleukin-6 and interferon-γ both failed to demonstrate a significant renal effect. For several other targets, preclinical data are encouraging but will require confirmation. We envision that high-throughput technologies will enable accurate patient stratification, thus offering the opportunity for personalized implementation of cytokine-targeting therapies.

    更新日期:2019-09-06
  • Extensive serum biomarker analysis in patients with macrophage activation syndrome associated with systemic lupus erythematosus
    Clin. Immunol. (IF 3.548) Pub Date : 2019-08-30
    Masaaki Usami, Masaki Shimizu, Mao Mizuta, Natsumi Inoue, Hitoshi Irabu, Naoto Sakumura, Yasuo Nakagishi, Akihiro Yachie

    The present study employed an antibody array that simultaneously detects 174 cytokines to identify cytokines involved in the development of macrophage activation syndrome (MAS) associated with systemic lupus erythematosus (SLE) with a view to elucidating potential predictive markers. Eight SLE patients, including four with MAS, were analyzed. Levels of 31 cytokines were significantly elevated in the MAS phase compared with those in the active phase of SLE. Among these cytokines, the MAS/active phase ratios of CXCL9 and soluble tumor necrosis factor receptor II (sTNFR-II) were highest. Elevated serum CXCL9 and sTNFR-II levels during the MAS phase were confirmed by ELISA and were strongly correlated with other inflammatory markers, reflecting the disease activity of MAS associated with SLE. These results highlight the clinical significance of serum CXCL-9 and sTNFR-II levels, and indicate they may be useful biomarkers for the diagnosis of MAS associated with SLE.

    更新日期:2019-08-31
  • The novel cytokine Metrnl/IL-41 is elevated in psoriatic arthritis synovium and induced at the enthesis
    Clin. Immunol. (IF 3.548) Pub Date : 2019-08-27
    Charlie Bridgewood, Tobias Russell, Helen Weedon, Thomas Baboolal, Abdulla Watad, Kassem Sharif, Richard Cuthbert, Miriam Wittmann, Mihir Wechalekar, Dennis McGonagle

    Abstract Meteorin-like(IL-41), is a novel cytokine that is thought to be immunoregulatory and is highly expressed in psoriatic skin. We investigated IL-41 protein expression in synovial tissue in RA(Rheumatoid Arthritis), PsA(Psoriatic Arthritis) and OA(Osteoarthritis) patients and evaluated IL-41 production from healthy enthesis samples, as the enthesis represent the primary inflammatory lesion in PsA. IL-41 was measured in synovial fluid from PsA, RA and OA patients. Synovial biopsies were stained for IL-41 by immunohistochemistry. IL-41 was highly expressed in the synovial fluid and synovial tissue of PsA patients (median = 8118 pg/ml) when compared to OA patients (median = 4720 pg/ml). We found that entheseal stromal cells were the dominant producer of IL-41 from the enthesis. Moreover, stromal derived IL-41, could be further induced by IL-17A/F and TNF. In conclusion, IL-41 is expressed in PsA synovium and is present and inducible at the enthesis. Its functional effect in psoriatic inflammation remains to be fully elucidated.

    更新日期:2019-08-27
  • Pregnancy-related immune suppression leads to altered influenza vaccine recall responses
    Clin. Immunol. (IF 3.548) Pub Date : 2019-08-27
    Nishel M. Shah, Nesrina Imami, Peter Kelleher, Wendy S. Barclay, Mark R. Johnson

    Pregnancy is a risk factor for severe influenza infection. Despite achieving seroprotective antibody titres post immunisation fewer pregnant women experience a reduction in influenza-like illness compared to non-pregnant cohorts. This may be due to the effects that immune-modulation in pregnancy has on vaccine efficacy leading to a less favourable immunologic response. To understand this, we investigated the antigen-specific cellular responses and leukocyte phenotype in pregnant and non-pregnant women who achieved seroprotection post immunisation. We show that although pregnancy is associated with better antigen-specific inflammatory (IFN-γ) responses and an expansion of central memory T cells (Tcm) post immunisation, but low-level pregnancy-related immune regulation (HLA-G, PIBF) and associated reduced B-cell antibody maintenance (TGF-β) suggest poor immunologic responses compared to the non-pregnant. Thus far, studies of influenza vaccine immunogenicity have focused on the induction of antibodies but understanding additional vaccine-related cellular responses is needed to fully appreciate how pregnancy impacts on vaccine effectiveness.

    更新日期:2019-08-27
  • West Nile Virus infection triggering autoimmune encephalitis: Pathophysiological and therapeutic implications
    Clin. Immunol. (IF 3.548) Pub Date : 2019-08-24
    P. Karagianni, H. Alexopoulos, A. Sourdi, D. Papadimitriou, A.N. Dimitrakopoulos, H.M. Moutsopoulos

    Background A contributing factor in triggering autoimmune phenomena is pathogen infections. Here we describe a case that expands the spectrum of infection-associated autoimmune encephalitis and discuss plausible pathogenetic mechanisms. Design Case report and in silico analysis. Results A patient with West Nile Virus infection developed autoimmune encephalitis with positive anti-glycine receptor antibodies. Combination therapy with corticosteroids and intravenous immunoglobulin resulted in the resolution of encephalitis signs and symptoms. An in silico analysis unveiled certain sequence similarities between viral antigens and receptor sequence fragments suggesting a molecular mimicry autoimmunization process. Conclusions Our case indicates that West Nile Virus infections can trigger autoimmune encephalitis. Our finding expands the spectrum of autoimmune conditions that can develop following an infection. Whether the autoimmunization process is due to molecular mimicry or due to the expansion of natural autoantibody clones merits further investigation.

    更新日期:2019-08-25
  • Comparison of serum biomarkers for the diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis
    Clin. Immunol. (IF 3.548) Pub Date : 2019-08-23
    Maiko Takakura, Masaki Shimizu, Hitoshi Irabu, Naoto Sakumura, Natsumi Inoue, Mao Mizuta, Yasuo Nakagishi, Akihiro Yachie

    Our study aimed to compare the accuracy of serum biomarkers for the diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA). Serum cytokine levels (neopterin, IL-18, and CXCL9 and soluble tumor necrosis factor receptor type I (sTNFR-I) and II) were determined by enzyme-linked immunosorbent assay in 78 patients with s-JIA, including 21 with MAS. Receiver operating characteristic curve analysis revealed area under the curve values and cut off values of neopterin, IL-18, CXCL9, sTNFR-II/I ratio and ferritin were 0.9465/19.5 nmol/l, 0.8895/69250 ng/ml, 0.9333/3130 pg/ml, 0.9395/3.796 and 0.8671/2560 ng/ml, respectively. Serum neopterin levels were significantly elevated in patients with MAS and those were correlated positively with disease activity. In conclusion, serum neopterin levels may be used as a promising indicator of disease activity in s-JIA and MAS and for evaluating it. It may also be a useful marker to diagnose the transition to MAS from active-phase s-JIA.

    更新日期:2019-08-25
Contents have been reproduced by permission of the publishers.
导出
全部期刊列表>>
2020新春特辑
限时免费阅读临床医学内容
ACS材料视界
科学报告最新纳米科学与技术研究
清华大学化学系段昊泓
自然科研论文编辑服务
中国科学院大学楚甲祥
中国科学院微生物研究所潘国辉
中国科学院化学研究所
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug