Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Front Immunol. 2021 Jan 15;11:612323. doi: 10.3389/fimmu.2020.612323. eCollection 2020.
There is paucity of literature on XLA from developing countries. Herein we report the clinical and molecular profile and outcome in a multicenter cohort of patients with XLA from India.
Data on XLA from all regional centers supported by the Foundation for Primary Immunodeficiency Diseases (FPID), USA and other institutions providing care to patients with PIDs were collated. Diagnosis of XLA was based on European Society for Immunodeficiencies (ESID) criteria.
We received clinical details of 195 patients with a provisional diagnosis of XLA from 12 centers. At final analysis, 145 patients were included (137 'definite XLA' and eight 'probable/possible XLA'). Median age at onset of symptoms was 12.0 (6.0, 36.0) months and median age at diagnosis was 60.0 (31.5, 108) months. Pneumonia was the commonest clinical manifestation (82.6%) followed by otitis media (50%) and diarrhea (42%). Arthritis was seen in 26% patients while 23% patients developed meningitis. Bronchiectasis was seen in 10% and encephalitis (likely viral) in 4.8% patients. was the commonest bacterial pathogen identified followed by , and . Molecular analysis revealed 86 variants in 105 unrelated cases. Missense variants in gene were the most common (36%) followed by frameshift (22%) and nonsense variants (21%). Most pathogenic gene variants (53%) were clustered in the distal part of gene encompassing exons 14-19 encoding for the tyrosine kinase domain. Follow-up details were available for 108 patients. Of these, 12% had died till the time of this analysis. The 5-year and 10-year survival was 89.9% and 86.9% respectively. Median duration of follow-up was 61 months and total duration of follow-up was 6083.2 patient-months. All patients received intravenous immunoglobulin (IVIg) replacement therapy. However, in many patients IVIg could not be given at recommended doses or intervals due to difficulties in accessing this therapy because of financial reasons and lack of universal health insurance in India. Hematopoietic stem cell transplant was carried out in four (2.8%) patients.
There was a significant delay in the diagnosis and facilities for molecular diagnosis were not available at many centers. Optimal immunoglobulin replacement is still a challenge.
发展中国家关于 XLA 的文献很少。在此，我们报告了来自印度的多中心 XLA 患者队列的临床和分子特征及结果。
收集了由美国原发性免疫缺陷疾病基金会（FPID）和其他为 PID 患者提供治疗的机构支持的所有区域中心的 XLA 数据。XLA 的诊断基于欧洲免疫缺陷学会（ESID）标准。
我们从 12 个中心收到了 195 例疑似 XLA 患者的临床详细信息。最终分析时，纳入了 145 例患者（137 例“明确的 XLA”和 8 例“可能的 XLA”）。症状发作的中位年龄为 12.0（6.0，36.0）个月，诊断的中位年龄为 60.0（31.5，108）个月。肺炎是最常见的临床表现（82.6%），其次是中耳炎（50%）和腹泻（42%）。关节炎见于 26%的患者，23%的患者发生脑膜炎。支气管扩张见于 10%的患者，脑炎（可能是病毒）见于 4.8%的患者。最常见的细菌病原体是 ，其次是 、 。分子分析显示，在 105 例无关联病例中发现了 86 种变异。 基因中的错义变异最为常见（36%），其次是移码（22%）和无义变异（21%）。大多数致病性基因变异（53%）聚集在基因的远端，包含编码酪氨酸激酶结构域的外显子 14-19。108 例患者可获得随访详情。其中，分析时已有 12%的患者死亡。5 年和 10 年生存率分别为 89.9%和 86.9%。中位随访时间为 61 个月，总随访时间为 6083.2 患者月。所有患者均接受静脉注射免疫球蛋白（IVIg）替代治疗。然而，由于经济原因和印度缺乏全民健康保险，许多患者无法获得这种治疗，导致无法按照推荐剂量或间隔使用 IVIg。有 4 例（2.8%）患者接受了造血干细胞移植。
诊断存在显著延迟，许多中心缺乏分子诊断设施。最佳的免疫球蛋白替代治疗仍然是一个挑战。
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