Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score.,Journal of Allergy and Clinical Immunology

当前位置： X-MOL 学术 › J. Allergy Clin. Immunol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score.
Journal of Allergy and Clinical Immunology ( IF 11.4 ) Pub Date : 2019-12-27 , DOI: 10.1016/j.jaci.2019.12.896
Victoria Katharina Tesch ₁ , Hassan Abolhassani ₂ , Bella Shadur ₃ , Joachim Zobel ₄ , Yuliya Mareika ₅ , Svetlana Sharapova ₆ , Elif Karakoc-Aydiner ₇ , Jacques G Rivière ₈ , Marina Garcia-Prat ₈ , Nicolette Moes ₉ , Filomeen Haerynck ₁₀ , Luis I Gonzales-Granado ₁₁ , Juan Luis Santos Pérez ₁₂ , Anna Mukhina ₁₃ , Anna Shcherbina ₁₃ , Asghar Aghamohammadi ₁₄ , Lennart Hammarström ₁₅ , Figen Dogu ₁₆ , Sule Haskologlu ₁₆ , Aydan I İkincioğulları ₁₆ , Sevgi Köstel Bal ₁₇ , Safa Baris ₇ , Sara Sebnem Kilic ₁₈ , Neslihan Edeer Karaca ₁₉ , Necil Kutukculer ₁₉ , Hermann Girschick ₂₀ , Antonios Kolios ₂₁ , Sevgi Keles ₂₂ , Vedat Uygun ₂₂ , Polina Stepensky ₂₃ , Austen Worth ₂₄ , Joris M van Montfrans ₂₅ , Anke M J Peters ₂₆ , Isabelle Meyts ₂₇ , Mehdi Adeli ₂₈ , Antonio Marzollo ₂₉ , Nurcicek Padem ₃₀ , Amer M Khojah ₃₀ , Zahra Chavoshzadeh ₃₁ , Magdalena Avbelj Stefanija ₃₂ , Shahrzad Bakhtiar ₃₃ , Benoit Florkin ₃₄ , Marie Meeths ₃₅ , Laura Gamez ₃₆ , Bodo Grimbacher ₃₇ , Mikko R J Seppänen ₃₈ , Arjan Lankester ₃₉ , Andrew R Gennery ₄₀ , Markus G Seidel ₁ ,

Affiliation

Research Unit for Pediatric Hematology and Immunology, Medical University Graz, Graz, Austria; Division of Pediatric Hemato-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria.
Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran.
Department of Bone Marrow Transplantation, Hadassah, Hebrew University Medical Centre, Jerusalem, Israel; Garvan Institute of Medical Research, Department of Immunology, Darlinghurst, Australia.
Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria.
Bone Marrow Transplantation Unit, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus.
Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus.
Faculty of Medicine, Pediatric Immunology and Allergy Division, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.
Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain; Jeffrey Modell Foundation Excellence Center, Barcelona, Spain.
Department of Pediatric Gastroenterology, Antwerp University Hospital, Edegem, and Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium.
Primary Immune Deficiency Research Lab and Department of Internal Medicine and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium.
Immunodeficiencies Unit, Hospital 12 de Octubre, Research Institute Hospital 12 Octubre (i+12), Madrid, Spain.
Infectious Diseases and Immunodeficiencies Unit, Service of Pediatrics, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Immunology, the Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran.
Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey.
Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria.
Pediatric Immunology-Rheumatology, Medical Faculty Department of Pediatrics, Uludag University Bursa, Bursa, Turkey.
Ege University Faculty of Medicine, Department of Pediatric Immunology, Izmir, Turkey.
Children's Hospital, Vivantes Berlin Friedrichshain, Berlin, Germany.
Department of Immunology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
Meram Medical Faculty, Division of Pediatric Allergy and Immunology, Necmettin Erbakan University, Konya, Turkey.
Department of Bone Marrow Transplantation, Hadassah, Hebrew University Medical Centre, Jerusalem, Israel.
Institute of Child Health, University College London, London, United Kingdom.
Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, UMC Utrecht, The Netherlands.
Department of Pediatric Hematology and Oncology, Center for Pediatrics, Medical Center-University of Freiburg, Freiburg, Germany.
Department of Pediatrics, University Hospitals Leuven, and the Laboratory for Inborn Errors of Immunity, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Sidra Medicine/Hamad Medical Corporation, Doha, Qatar.
Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, Azienda Ospedaliera-University of Padova, Padova, Italy.
Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Ill.
Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Pediatric Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Division for Stem Cell Transplantation and Immunology, University Hospital Frankfurt, Frankfurt, Germany.
Immuno-Hémato-Rhumatologie Pédiatrique, Service de Pédiatrie, CHR Citadelle, Liege, Belgium.
Childhood Cancer Research Unit, Department of Women's and Children's Health and Clinical Genetics Unit, Department of Molecular Medicine and Surgery, and Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital Solna, Stockholm, Sweden.
Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany; DZIF-German Center for Infection Research, Satellite Center Freiburg, Freiburg, Germany; Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University, Freiburg, Germany; RESIST-Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany.
Rare Diseases Center and Pediatric Research Center, Children and Adolescents, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland; Adult Immunodeficiency Unit, Inflammation Center, University of Helsinki, and HUS Helsinki University Hospital, Helsinki, Finland; Translational Immunology, Research Programs Unit and Clinicum, University of Helsinki, Helsinki, Finland.
Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.

BACKGROUND Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. OBJECTIVE This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. METHOD We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. RESULTS Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. CONCLUSION The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.

中文翻译：

根据免疫缺陷和失调活性（IDDA）评分评估，采用各种治疗方式后，76例患者的LRBA缺乏症的长期结局。

背景技术最近的发现强烈支持严重表现为LPS反应性米色样锚蛋白（LRBA）缺乏症的患者的造血干细胞移植（HSCT），但长期的随访和生存数据超出了先前的患者报告或荟萃评价。对于那些没有接受移植的患者而言稀缺。目的进行这项国际回顾性研究，以阐明接受和不接受移植的LRBA缺乏症患者的纵向临床病程。方法我们通过特别开发的免疫缺陷和失调活动评分评估疾病负担和治疗反应，反映出器官受累和感染的总数和严重程度，住院天数，支持治疗的要求以及性能指标。结果：29个中心的76例LRBA缺乏症患者（中位随访时间为10年；范围为1-52），2005年至2019年接受了24例HSCT。HSCT术后总体生存率（中位随访时间为20个月）为70.8％（24名患者中的17名）; 所有死亡均归因于与移植相关的早期非特异性死亡。目前，未接受移植的患者中有82.7％（52岁的患者中有43岁；年龄在3-69岁之间）还活着。在17名HSCT幸存者中，7例完全缓解，5例未经治疗而部分缓解良好（总共17人中有12人[70.6％]）。相比之下，未接受移植的43位患者中只有5位（11.6％）没有免疫抑制。在HSCT中幸存的患者的免疫缺陷和失调活动评分显着低于接受常规治疗的患者（P = 0。005）或接受abatacept或西罗莫司治疗（与其他疗法相比）的患者，以及残留LRBA表达的患者。较高的疾病负担，HSCT之前的持续时间较长以及肺部受累与不良预后相关。结论必须权衡终生疾病活动性，这意味着需要免疫抑制和恶性肿瘤的风险，必须权衡HSCT的风险。

更新日期：2019-12-27

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11