哥伦比亚队列中X连锁无丙种球蛋白血症的临床和遗传特征

文献信息

中文摘要

引言： X连锁无丙种球蛋白血症（XLA）是一种由BTK基因突变引起的先天性免疫缺陷（IEI），导致成熟B细胞缺失和血清免疫球蛋白水平改变。在哥伦比亚，缺乏统一的流行病学和遗传学数据。本研究旨在从人口学、表型和基因型方面描述该国XLA患者的特征。
方法： 一项基于临床记录的多中心、观察性、横断面研究。纳入38例B细胞计数<2%且伴有低丙种球蛋白血症的患者。使用R-Studio中的描述性统计分析临床、免疫学和遗传学变量及结局。
结果： 分析了38例男性患者，诊断时中位年龄为16个月（IQR 7.2-21.8）。84.2%（n=32）的患者可获得基因检测，鉴定出15种不同的变异，其中53%为新发变异。鼻窦肺部感染是主要表现（92.1%），尤其是肺炎（42.1%）和中耳炎（39.5%）。基线IgG中位水平为187 mg/dL。34.2%的病例记录有支气管扩张。八年生存率为71.1%。
讨论： 哥伦比亚队列显示诊断相对较早，但结构性后遗症（支气管扩张）负担较高，提示需要优化免疫球蛋白替代治疗。新发遗传变异比例高，凸显了区域研究的重要性。本研究代表了哥伦比亚对XLA最全面的特征描述，为改进临床怀疑和预后提供了关键数据。

英文摘要

INTRODUCTION: X-linked Agammaglobulinemia (XLA) is an inborn error of immunity (IEI) caused by mutations in the BTK gene, resulting in the absence of mature B-cells and altered serum immunoglobulin levels. In Colombia, unified epidemiological and genetic data are lacking. This study aims to characterize XLA patients in the country demographically, phenotypically, and genotypically.
METHODS: A multicenter, observational, cross-sectional study based on clinical records. Thirty-eight patients with B-cell counts <2% and hypogammaglobulinemia were included. Clinical, immunological, and genetic variables and outcomes were analyzed using descriptive statistics in R-Studio.
RESULTS: Thirty-eight males were analyzed, with a median age at diagnosis of 16 months (IQR 7.2-21.8). Genetic testing was available for 84.2% (n = 32), identifying 15 distinct variants, 53% of which were novel. Sinopulmonary infections were the primary manifestation (92.1%), notably pneumonia (42.1%) and otitis media (39.5%). Median baseline IgG levels were 187 mg/dL. Bronchiectasis was documented in 34.2% of cases. The eight-year survival rate was 71.1%.
DISCUSSION: The Colombian cohort shows a relatively early diagnosis but a high burden of structural sequelae (bronchiectasis), suggesting a need to optimize immunoglobulin replacement therapy. The high proportion of novel genetic variants underscores the importance of regional studies. This study represents the most robust characterization of XLA in Colombia, providing key data to improve clinical suspicion and prognosis.