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Abstract

Common variable immunodeficiency (CVID) is a very heterogeneous syndrome defined by impaired immunoglobulin production. The functional classification of CVID patients on the basis of in vitro immunoglobulin production is time consuming and has never shown any predictive value. We propose a classification based on the quantitative repartition of naive/memory B cells according to the dual expression of IgD and CD27. Fifty-seven patients were categorized into three groups: Group MB2 (11 patients, 19%) with normal memory B cells; Group MB1 (19 patients, 33%) with defective switched memory (IgD-CD27+) but normal nonswitched memory B cells (IgD+CD27+); Group MB0 (27 patients, 47%) with almost no memory B cells. In addition, a downexpression of activation markers (CD25, CD21, CD80, CD86) on B cells characterized the group MB1 patients and was associated with an upexpression of activation markers (HLA-DR, CD95, CD57) on T cells. This classification correlates with some clinical aspects showing a higher prevalence of splenomegaly (16/27, 59%), lymphoid proliferation (13/27, 48%) and granulomatous disease (12/27, 44%) in group MB0. Splenomegaly was also frequent in group MB1 (8/19, 42%). In contrast, autoimmunity was observed with similar prevalence in all three groups. Moreover, by analyzing B cell phenotype, immunoglobulin transcript expression, and somatic mutations, we propose different putative mechanisms responsible for impaired B cell activation and memory differentiation in this syndrome.

Common Variable Immunodeficiency: Etiological and Treatment Issues

“…Beginning in 2002, efforts to subclassify CVID based on B cell characteristics were proposed by separate groups in Freiburg and Paris [92,93]. Both criteria included analysis of CD27+ B cell subsets, while the Paris protocol additionally included evaluation of total CD27+ B cells and the Freiburg protocol added the evaluation of CD21 expression [92,93,94].…”

“…Both criteria included analysis of CD27+ B cell subsets, while the Paris protocol additionally included evaluation of total CD27+ B cells and the Freiburg protocol added the evaluation of CD21 expression [92,93,94]. The 2 guidelines have now been unified in the Euroclass consensus classification (table 6) which first separates the small group of CVID patients with essentially no circulating B cells from the remainder of the population.…”

Analysis of Switched Memory B Cells in Patients with IgA Deficiency

“…Switched memory B cells were first found to be absent in X-linked hyper-IgM syndrome [17]. Subsequently, a number of reports have described a reduction in CD27+ memory B cells in peripheral blood from patients with CVID [18,19,20,21,22]. Warnatz et al [18] divided CVID patients into 2 groups based on switched memory B cells in peripheral blood lymphocytes (PBLs).…”

Flow Cytometry, a Versatile Tool for Diagnosis and Monitoring of Primary Immunodeficiencies

“…cluding susceptibility to sinopulmonary infections, granulomatous disease, lymphoproliferation, and autoimmunity (in subsets of patients) (88)(89)(90). Attempts have been made over the past decade or longer to classify CVID patients based on differences in peripheral B cell subsets, and some of these have provided clinical correlations, which may have prognostic value in subgroups of patients (91)(92)(93)(94)(95)(96)(97)(98). B cell subset analysis, in particular evaluation of memory B cells and switched memory B cells, has been incorporated into the newer diagnostic criteria as an accessory criterion (88), as the majority of CVID patients have impaired peripheral B cell differentiation and reduced class-switched memory B cells.…”