Sheffield Children's NHS Foundation Trust, Sheffield, UK.
Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
J Clin Immunol. 2024 Nov 14;45(1):40. doi: 10.1007/s10875-024-01829-z.
X-linked agammaglobulinaemia (XLA), caused by mutations in BTK, is characterised by low or absent peripheral CD19 + B lymphocytes and agammaglobulinaemia. The mainstay of treatment consists of immunoglobulin replacement therapy (IgRT). As this cannot fully compensate for the immune defects in XLA, patients may therefore continue to be at risk of complications.
To describe the clinical outcomes of XLA patients in the United Kingdom and Hong Kong and evaluate current treatment strategies.
Patients with a definitive diagnosis of XLA were included in this cross-sectional and retrospective analysis of clinical health outcomes. Data pertaining to diagnosis, infection incidence, IgG trough levels and lung function were collected and analysed.
99 patients with a median age of 29.02 years (IQR 12.83-37.41) and a total follow up of 1922 patient years, were included this study. The median age at diagnosis was 3.30 years (IQR 1.04-8.38) which decreased over time (p = 0.004). 40% of the cohort had radiological evidence of bronchiectasis. Risk of bronchiectasis was not significantly associated with clinical infection incidence (p = 0.880) or IgG trough levels (p = 0.407). Two patients demonstrated novel complications, namely persistent norovirus infection, leading to haemopoietic stem cell transplantation (HSCT).
Despite modern therapy, most XLA patients continue to experience complications, most notably bronchiectasis, likely due to absence of IgA/M in current therapies, but lack of B lymphocytes may also lead to additional sequalae. These data strongly support the need for further research, particularly that of curative modalities including HSCT and gene therapy.
X 连锁无丙种球蛋白血症（XLA）由 BTK 突变引起，其特征是外周血 CD19+ B 淋巴细胞减少或缺失以及丙种球蛋白缺乏症。治疗的主要方法是免疫球蛋白替代疗法（IgRT）。由于这不能完全补偿 XLA 中的免疫缺陷，因此患者可能仍然存在并发症的风险。
描述英国和中国香港的 XLA 患者的临床结局，并评估当前的治疗策略。
本横断面回顾性分析了 XLA 患者的临床健康结局，纳入了明确诊断为 XLA 的患者。收集并分析了与诊断、感染发生率、IgG 谷底水平和肺功能相关的数据。
本研究共纳入了 99 名中位年龄为 29.02 岁（IQR 12.83-37.41）、总随访时间为 1922 患者年的患者。诊断时的中位年龄为 3.30 岁（IQR 1.04-8.38），随着时间的推移逐渐降低（p=0.004）。40%的患者存在支气管扩张的放射学证据。支气管扩张的风险与临床感染发生率（p=0.880）或 IgG 谷底水平（p=0.407）无显著相关性。两名患者出现了新的并发症，即持续性诺如病毒感染，导致造血干细胞移植（HSCT）。
尽管采用了现代疗法，大多数 XLA 患者仍持续出现并发症，最常见的是支气管扩张，这可能是由于目前的治疗方法缺乏 IgA/M，但缺乏 B 淋巴细胞也可能导致其他后遗症。这些数据强烈支持进一步研究的必要性，特别是包括 HSCT 和基因治疗在内的根治性方法的研究。
