{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T09:12:54Z","timestamp":1791882774658,"version":"4.3.4"},"reference-count":53,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,3,1]]},"abstract":"<jats:p>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\u2212IgD\u2212 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\u2212 peripheral B cells (&amp;gt;\u200920%; group Ia) and patients with normal percentages of CD21\u2212 B cells (&amp;lt;\u200920%; 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\u2013oriented 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.<\/jats:p>","DOI":"10.1182\/blood.v99.5.1544","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:40Z","timestamp":1027774000000},"page":"1544-1551","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":520,"title":["Severe deficiency of switched memory B cells (CD27+IgM\u2212IgD\u2212) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease"],"prefix":"10.1182","volume":"99","author":[{"given":"Klaus","family":"Warnatz","sequence":"first","affiliation":[{"name":"From the Division of Rheumatology and Clinical Immunology, Department of Medicine, and from the Department of Surgery, University Hospital of Freiburg, 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Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Groth","sequence":"additional","affiliation":[{"name":"From the Division of Rheumatology and Clinical Immunology, Department of Medicine, and from the Department of Surgery, University Hospital of Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Wolff-Vorbeck","sequence":"additional","affiliation":[{"name":"From the Division of Rheumatology and Clinical Immunology, Department of Medicine, and from the Department of Surgery, University Hospital of Freiburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Eibel","sequence":"additional","affiliation":[{"name":"From the Division of Rheumatology and Clinical Immunology, Department of Medicine, and from the Department of Surgery, University Hospital of Freiburg, 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