Long-term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality.,Journal of Allergy and Clinical Immunology

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Long-term follow-up of 168 patients with X-linked agammaglobulinemia reveals increased morbidity and mortality.
Journal of Allergy and Clinical Immunology ( IF 11.4 ) Pub Date : 2020-03-10 , DOI: 10.1016/j.jaci.2020.03.001
Vassilios Lougaris ₁ , Annarosa Soresina ₂ , Manuela Baronio ₁ , Davide Montin ₃ , Silvana Martino ₃ , Sara Signa ₄ , Stefano Volpi ₄ , Marco Zecca ₅ , Maddalena Marinoni ₆ , Lucia Augusta Baselli ₇ , Rosa Maria Dellepiane ₇ , Maria Carrabba ₈ , Giovanna Fabio ₈ , Maria Caterina Putti ₉ , Francesco Cinetto ₁₀ , Claudio Lunardi ₁₁ , Luisa Gazzurelli ₁ , Alessio Benvenuto ₁ , Patrizia Bertolini ₁₂ , Francesca Conti ₁₃ , Rita Consolini ₁₄ , Silvia Ricci ₁₅ , Chiara Azzari ₁₅ , Lucia Leonardi ₁₆ , Marzia Duse ₁₆ , Federica Pulvirenti ₁₇ , Cinzia Milito ₁₇ , Isabella Quinti ₁₇ , Caterina Cancrini ₁₈ , Andrea Finocchi ₁₈ , Viviana Moschese ₁₉ , Emilia Cirillo ₂₀ , Ludovica Crescenzi ₂₁ , Giuseppe Spadaro ₂₁ , Carolina Marasco ₂₂ , Angelo Vacca ₂₂ , Fabio Cardinale ₂₃ , Baldassare Martire ₂₄ , Antonino Trizzino ₂₅ , Maria Licciardello ₂₆ , Fausto Cossu ₂₇ , Gigliola Di Matteo ₁₈ , Raffaele Badolato ₁ , Simona Ferrari ₂₈ , Silvia Giliani ₂₉ , Andrea Pession ₁₃ , Alberto Ugazio ₃₀ , Claudio Pignata ₂₀ , Alessandro Plebani ₁

Affiliation

Pediatrics Clinic and Institute for Molecular Medicine A. Nocivelli, Department of Clinical and Experimental Sciences, University of Brescia and ASST-Spedali Civili di Brescia, Brescia, Italy.
Pediatrics Clinic, ASST- Spedali Civili of Brescia, Brescia, Italy.
Division of Pediatric Immunology and Rheumatology, Department of Public Health and Pediatrics, Regina Margherita Children Hospital, University of Turin, Turin, Italy.
Centro Malattie Autoinfiammatorie e Immunodeficienze-Clinica Pediatrica e Reumatologia, IRCCS Giannina Gaslini, Genova, and Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università di Genova, Genoa, Italy.
Department of Pediatric Hematology of Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Paediatric Department, ASST-Sette Laghi, F. Del Ponte Hospital, Varese, Italy.
Department of Pediatrics, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
Department of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Department of Women's and Children's Health, Pediatric Hematology-Oncology Unit, University of Padova, Padua, Italy.
Padua University, Department of Medicine (DIMED), Internal Medicine I and Rare Disease Center for Immunologic, Rheumatologic and Respiratory Diseases, Ca' Foncello Hospital, Treviso, Italy.
Department of Medicine, University of Verona, Verona, Italy.
Paediatric Hematology Oncology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy.
Unit of Pediatrics, University of Bologna, St. Orsola University Hospital, Bologna, Italy.
Section of Pediatrics Immunology and Rheumatology, Department of Pediatrics, University of Pisa, Pisa, Italy.
Department of Pediatric Immunology, Jeffrey Modell Center for Primary Immunodeficiency, Anna Meyer's Hospital, University of Florence, Florence, Italy.
Pediatrics Department, Umberto I Hospital, Sapienza University, Roma, Italy.
Department of Molecular Medicine, Sapienza University of Roma, and Unit of Primary Immunodeficiencies in Adults, Department of Infective diseases and Internal Medicine, Policlinico Umberto I, Rome, Italy.
University Department of Pediatrics, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital, University of Rome Tor Vergata, and the Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Department of Pediatrics, Policlinico Tor Vergata, Tor Vergata University, Rome, Italy.
Pediatric Section, Department of Translational Medical Science, Federico II University, Naples, Italy.
Department of Translational Medical Sciences, Allergy and Clinical Immunology Center for Basic and Clinical Immunology Research, University of Naples Federico II, Naples, Italy.
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
Department of Pediatrics and Emergency, Pediatric Allergy and Pulmunology Unit, Azienda Ospedaliera-Universitaria Consorziale-Policlinico, Ospedale Pediatrico Giovanni XXIII, Bari, Italy.
Pediatric Unit, Monsignor Dimiccoli Hospital, Barletta, Italy.
Department of Pediatric Hematology and Oncology, ARNAS Civico Di Cristina and Benfratelli Hospital, Palermo, Italy.
Haematology of Oncology Unit, Department of Pediatrics, University of Catania- Catania, Italy.
Second Pediatric Clinic, Antonio Cao Hospital, University of Cagliari, Cagliari, Italy.
Unit of Medical Genetics, St. Orsola University Hospital, University of Bologna, Bologna, Italy.
Department of Molecular and Translational Medicine, A. Nocivelli Institute for Molecular Medicine, University of Brescia, Brescia, Italy.
Institute of Child and Adolescent Health, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Background

X-linked agammaglobulinemia (XLA) is the prototype of primary humoral immunodeficiencies. Long-term follow-up studies regarding disease-related complications and outcome are scarce.

Objective

Our aim was to describe the natural history of XLA.

Methods

A nationwide multicenter study based on the Italian Primary Immunodeficiency Network registry was established in 2000 in Italy. Affected patients were enrolled by documenting centers, and the patients’ laboratory, clinical, and imaging data were recorded on an annual base.

Results

Data on the patients (N = 168) were derived from a cumulative follow-up of 1370 patient-years, with a mean follow-up of 8.35 years per patient. The mean age at diagnosis decreased after establishment of the Italian Primary Immunodeficiency Network registry (84 months before vs 23 months after). Respiratory, skin, and gastrointestinal manifestations were the most frequent clinical symptoms at diagnosis and during long-term follow-up. Regular immunoglobulin replacement treatment reduced the incidence of invasive infections. Affected patients developed chronic lung disease over time (47% after 40 years of follow-up) in the presence of chronic sinusitis (84%). Malignancies were documented in a minority of cases (3.7%). Overall survival for affected patients was significantly reduced when compared with that for the healthy male Italian population, and it further deteriorated in the presence of chronic lung disease.

Conclusions

This is the first detailed long-term follow-up study for patients with XLA, revealing that although immunoglobulin replacement treatment reduces the incidence of invasive infections, it does not appear to influence the development of chronic lung disease. The overall survival of affected patients is reduced. Further studies are warranted to improve patients’ clinical management and increase awareness among physicians.

中文翻译：

168例X连锁性丙种球蛋白血症的长期随访显示发病率和死亡率增加。

背景

X连锁的丙种球蛋白血症（XLA）是原发性体液免疫缺陷的原型。缺乏有关疾病相关并发症和结果的长期随访研究。

目的

我们的目的是描述XLA的自然历史。

方法

2000年在意大利建立了基于意大利主要免疫缺陷网络注册中心的全国性多中心研究。记录中心招募了患病患者，并每年记录患者的实验室，临床和影像数据。

结果

有关患者的数据（N = 168）来自对1370个患者-年的累计随访，平均每个患者8.35年的随访。建立意大利主要免疫缺陷网络注册机构后，诊断时的平均年龄有所下降（之前的84个月对之后的23个月）。呼吸，皮肤和胃肠道表现是诊断和长期随访中最常见的临床症状。定期进行免疫球蛋白替代治疗可减少侵入性感染的发生。在存在慢性鼻窦炎（84％）的情况下，患病患者随着时间的流逝发展为慢性肺部疾病（在40年的随访中占47％）。少数病例（3.7％）记录了恶性肿瘤。与健康的意大利男性人群相比，受影响患者的总体生存率显着降低，