Department of Infectious Diseases and Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
J Clin Immunol. 2013 Aug;33(6):1067-77. doi: 10.1007/s10875-013-9893-2. Epub 2013 May 7.
Common variable immunodeficiency (CVID) comprises a heterogeneous group of primary immunodeficiency disorders. Immunophenotyping of memory B cells at the time of diagnosis is increasingly used for the classification of patients into subgroups with different clinical prognoses. The EUROclass classification is a widely used method. Levels of somatic hypermutation (SHM) have proven useful as a prognostic marker for recurrent respiratory tract infections. As time of presentation and diagnosis is highly variable in CVID patients, and diagnostic delay is a common problem, it is important to know whether classification parameters are stable over time. The purpose of the study was to address this question in a cohort of 33 CVID patients followed from 3 to 19 years after diagnosis (average follow-up 8.8 years).
Levels of class-switched memory B cells were analyzed using flow cytometric immunophenotyping, and patients were classified according to the EUROclass criteria. Affinity maturation of B cells was measured using Igκ-REHMA, which assesses somatic hypermutation in kappa light chain transcripts. Clinical manifestations in terms of splenomegaly, autoimmune disease and granulomatous disease were also determined.
Switched memory B cells and levels of SHM were not consistently stable markers in a long-term follow-up setting. At a given time during follow-up, 60% of the patients were assigned to the EUROclass group SmB- (less than 2% switched memory B cells), but only 23% were consistently assigned to this group. Associations between clinical manifestations and levels of switched memory B cells or SHM were not observed in our study.
Based on our findings, we suggest that immunologic characteristics in CVID patients should be evaluated several times after diagnosis using internationally standardized methods.
普通变异型免疫缺陷病（CVID）是一组异质性原发性免疫缺陷病。在诊断时对记忆 B 细胞进行免疫表型分析，越来越多地用于将患者分为具有不同临床预后的亚组。EUROclass 分类是一种广泛使用的方法。体细胞高频突变（SHM）水平已被证明可作为复发性呼吸道感染的预后标志物。由于 CVID 患者的就诊时间和诊断时间高度可变，且诊断延迟是一个常见问题，因此了解分类参数是否随时间稳定非常重要。本研究的目的是在一组 33 例 CVID 患者中进行研究，这些患者在诊断后 3 至 19 年（平均随访 8.8 年）进行随访。
使用流式细胞术免疫表型分析来分析类别转换的记忆 B 细胞，并根据 EUROclass 标准对患者进行分类。使用 Igκ-REHMA 测量 B 细胞的亲和力成熟，该方法评估κ轻链转录物中的体细胞高频突变。还确定了脾肿大、自身免疫性疾病和肉芽肿性疾病等临床表现。
在长期随访中，转换的记忆 B 细胞和 SHM 水平不是稳定的标志物。在随访期间的某个时间点，60%的患者被分配到 EUROclass 组 SmB-（少于 2%的转换记忆 B 细胞），但只有 23%的患者始终被分配到该组。在我们的研究中，未观察到临床表现与转换的记忆 B 细胞或 SHM 之间的关联。
根据我们的发现，我们建议使用国际标准化方法在诊断后多次评估 CVID 患者的免疫学特征。
