Wehr Claudia, Kivioja Teemu, Schmitt Christian, Ferry Berne, Witte Torsten, Eren Efrem, Vlkova Marcela, Hernandez Manuel, Detkova Drahomira, Bos Philip R, Poerksen Gonke, von Bernuth Horst, Baumann Ulrich, Goldacker Sigune, Gutenberger Sylvia, Schlesier Michael, Bergeron-van der Cruyssen Florence, Le Garff Magali, Debré Patrice, Jacobs Roland, Jones John, Bateman Elizabeth, Litzman Jiri, van Hagen P Martin, Plebani Alessandro, Schmidt Reinhold E, Thon Vojtech, Quinti Isabella, Espanol Teresa, Webster A David, Chapel Helen, Vihinen Mauno, Oksenhendler Eric, Peter Hans Hartmut, Warnatz Klaus
Department of Rheumatology and Clinical Immunology, University Clinic, Freiburg, Germany.
Blood. 2008 Jan 1;111(1):77-85. doi: 10.1182/blood-2007-06-091744. Epub 2007 Sep 26.
The heterogeneity of common variable immunodeficiency (CVID) calls for a classification addressing pathogenic mechanisms as well as clinical relevance. This European multicenter trial was initiated to develop a consensus of 2 existing classification schemes based on flowcytometric B-cell phenotyping and the clinical course. The clinical evaluation of 303 patients with the established diagnosis of CVID demonstrated a significant coincidence of granulomatous disease, autoimmune cytopenia, and splenomegaly. Phenotyping of B-cell subpopulations confirmed a severe reduction of switched memory B cells in most of the patients that was associated with a higher risk for splenomegaly and granulomatous disease. An expansion of CD21(low) B cells marked patients with splenomegaly. Lymphadenopathy was significantly linked with transitional B-cell expansion. Based on these findings and pathogenic consideration of B-cell differentiation, we suggest an improved classification for CVID (EUROclass), separating patients with nearly absent B cells (less than 1%), severely reduced switched memory B cells (less than 2%), and expansion of transitional (more than 9%) or CD21(low) B cells (more than 10%). Whereas the first group contains all patients with severe defects of early B-cell differentiation, severely reduced switched memory B cells indicate a defective germinal center development as found in inducible constimulator (ICOS) or CD40L deficiency. The underlying defects of expanded transitional or CD21(low) B cells remain to be elucidated. This trial is re-gistered at http://www.uniklinik-freiburg.de/zks/live/uklregister/Oeffentlich.html as UKF000308.
普通可变免疫缺陷（CVID）的异质性要求进行一种既能涵盖致病机制又具有临床相关性的分类。这项欧洲多中心试验旨在基于流式细胞术B细胞表型分析和临床病程，对现有的两种分类方案达成共识。对303例确诊为CVID的患者进行临床评估发现，肉芽肿性疾病、自身免疫性血细胞减少和脾肿大之间存在显著相关性。B细胞亚群的表型分析证实，大多数患者的转换记忆B细胞严重减少，这与脾肿大和肉芽肿性疾病的较高风险相关。CD21（低表达）B细胞的扩增是脾肿大患者的特征。淋巴结病与过渡性B细胞扩增显著相关。基于这些发现以及对B细胞分化的致病机制考虑，我们建议对CVID进行改进分类（EUROclass），将几乎没有B细胞（少于1%）、转换记忆B细胞严重减少（少于2%）以及过渡性（超过9%）或CD21（低表达）B细胞扩增（超过10%）的患者区分开来。第一组包括所有早期B细胞分化严重缺陷的患者，转换记忆B细胞严重减少表明生发中心发育存在缺陷，如在诱导性共刺激分子（ICOS）或CD40L缺陷中所见。过渡性或CD21（低表达）B细胞扩增的潜在缺陷仍有待阐明。该试验已在http://www.uniklinik-freiburg.de/zks/live/uklregister/Oeffentlich.html上注册，注册号为UKF000308。
