title: Deficiency of somatic hypermutation of immunoglobulin G transcripts is a better predictor of severe respiratory tract infections than lack of memory B cells in common variable immunodeficiency.
abstract: Defects of memory B cells and of somatic hypermutation (SHM) are involved in the pathogenesis of common variable immunodeficiency (CVID). Here we report for the first time a systematic study of the relationship between memory B cell deficiency and SHM abnormalities in CVID, and relate these variables to prediagnostic infections. Isotype switched Vh3-23 transcripts were undetectable or low in 30% (IgG) and 63% (IgA) of the patients, but never in controls (P < 0.001). When measurable, the SHM fraction of transcripts was significantly lower in patients (IgM: median 32% vs. 56% (P = 0.0002); IgG: 72% vs. 87% (P = 0.0002); IgA: 81% vs. 88% (P = 0.04)). The concentration of switched (CD19+/CD27+/IgG+) and unswitched (CD19+/CD27+/IgM+/IgD+) memory cells was reduced in 75% and 58% of the patients, respectively. Patients with reduced concentrations of switched memory B cells had normal or low SHM, and only the IgG SHM fraction correlated with prediagnostic incidence of severe respiratory tract infections (P = 0.004).
authors.affiliation: Department of Clinical Immunology, Copenhagen University Hospital, Copenhagen, Denmark. laogpd@mobilixnet.dk
authors.forename: Lone
authors.initials: L
authors.lastname: Schejbel
authors.forename: Hanne
authors.initials: H
authors.lastname: Marquart
authors.forename: Vagn
authors.initials: V
authors.lastname: Andersen
authors.forename: Henrik
authors.initials: H
authors.lastname: Permin
authors.forename: Pernille
authors.initials: P
authors.lastname: Andersen
authors.forename: Arne
authors.initials: A
authors.lastname: Svejgaard
authors.forename: Torben
authors.initials: T
authors.lastname: Barington
mesh_terms: D000328:Adult; D000368:Aged; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology*; D017074:Common Variable Immunodeficiency / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012141:Respiratory Tract Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M