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Medline ® Abstract for Reference 39

of 'Autoimmune lymphoproliferative syndrome (ALPS): Clinical features and diagnosis'

Severe deficiency of switched memory B cells (CD27(+)IgM(-)IgD(-)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease.
Warnatz K, Denz A, Dräger R, Braun M, Groth C, Wolff-Vorbeck G, Eibel H, Schlesier M, Peter HH
Blood. 2002;99(5):1544.
Hypogammaglobulinemia is the hallmark of common variable immunodeficiency (CVID) syndrome, a heterogeneous disorder predisposing patients to recurrent bacterial infections. In this study, we investigated the peripheral B-cell compartment of 30 well-characterized CVID patients in comparison to 22 healthy controls. Flow cytometric analysis of peripheral blood lymphocytes revealed a reduction of class-switched CD27(+)IgM(-)IgD(-) memory B cells below 0.4% in 77% of our patients (group I), while this B-cell subpopulation exceeded 0.5% in all healthy donors and in 23% of CVID patients (group II). These results correlate well with the capacity of peripheral blood lymphocytes to produce immunoglobulins in vitro upon stimulation with Staphylococcus aureus Cowan I (SAC) plus interleukin-2 because the production of immunoglobulin G in vitro is entirely dependent on the presence of switched memory B cells. The subdivision of group I into patients with an increased proportion of CD21(-) peripheral B cells (>20%; group Ia) and patients with normal percentages of CD21(-) B cells (<20%; group Ib) revealed a significant clustering of patients with splenomegaly and autoimmune cytopenias in group Ia. Based on these observations, we propose a fast and reliablenew classification for CVID patients by flow cytometric quantification of class-switched memory and immature B cells in the peripheral blood of patients. Our results point toward defects at various stages of B-cell differentiation in CVID subgroups and support the value of a B-cell-oriented classification principle. A consensus on this new classification system will hopefully provide a tool for rapidly defining homogeneous subgroups of CVID for functional studies and genetic linkage analysis.
Division of Rheumatology and Clinical Immunology, Department of Medicine, University Hospital of Freiburg, Germany.