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.
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 reliable new 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.
Warnatz
Klaus
K
Division of Rheumatology and Clinical Immunology, Department of Medicine, University Hospital of Freiburg, Germany.
Denz
Axel
A
Dräger
Ruth
R
Braun
Moritz
M
Groth
Christoph
C
Wolff-Vorbeck
Guido
G
Eibel
Hermann
H
Schlesier
Michael
M
Peter
Hans Hartmut
HH
D000328:Adult; D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D017074:Common Variable Immunodeficiency / Q000145:classification* / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D017578:Immunoglobulin Class Switching; D007132:Immunoglobulin Isotypes / Q000032:analysis / Q000096:biosynthesis; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis / Q000276:immunology
D018941:Antigens, CD19; D007132:Immunoglobulin Isotypes; D007376:Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7