Intestinal B cell defects in common variable immunodeficiency

Abstract

SUMMARYThe humoral immune system of the small intestine of 17 patients with common variable immunodeficiency (CVID) was studied by immunohistology using antibodies specific for IgA 1,2, IgM, IgGl-4, the J chain and the secretory component (SC). IgAl,2+, IgG2+ and IgM* lamina propria B cells were totally lacking in 65% (11/17), 41% (7/17) and 18% (3/17) of CVID patients, respectively. One patient exhibited an isolated IgAl subclass deficiency. The proportion of plasma cells in conventionally stained histological sections of the same intestinal biopsies showed a close correlation with the numbers of IgA"*" and IgM+ cells. Considerable numbers of J chain-synthesizing cells were present in all patients with CVID, indicating the presence of early B cells unable to differentiate into immunoglobulin-producing plasma cells. Most of the patients with intestinal IgA and/or IgM defects strongly expressed the SC in their enterocytes, suggesting an immunoglobulinindependent regulation of the SC. Clinically, only CVID patients with intestinal IgA defects developed intestinal infections with Giardia lambtia, Campylobacter jejuni or Candida albicans. The outcome of in vitro immunoglobulin synthesis assays with peripheral blood lymphocytes did not predict the presence or absence of the respective isotype-producing B cells in the intestinal lamina propria. Thus, immunohistological examinations of intestinal biopsies are required to determine the extent of mucosal immunodeficiency in CVID patients.Keywords MALT intestinal immunoglobulins J chain common variable immunodeficiency secretory component

B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans

“…It is striking, however, that both BAFF-R-deficient patients had normal levels of IgA as well as IgA ϩ plasma cells in the gut (P1, Fig. 4A), which is a very unusual finding among CVID patients (10,11), as most CVID patients have neither serum IgA nor intestinal IgA ϩ plasma cells (20).…”

“…Thus, the presence of IgA ϩ plasma cells in the gut, which is a very unusual finding among CVID patients (10,11,20), emphasizes the BAFF-R-independent differentiation of mucosal IgA ϩ B cells in humans, as in mice (6,24).…”

A difficult diagnosis of coeliac disease: Repeat duodenal histology increases diagnostic yield in patients with concomitant causes of villous atrophy

“…In CVID. [8,11,[20][21][22][23][24], such as the absence of plasma cells and the presence of a polymorphonuclear infiltrate (PMNI) and graft-versus-host disease-like lesions (GVHDL).…”

Alteraciones inmunológicas en la inmunodeficiencia común variable

“…11 También se ha demostrado agotamiento de las células plasmáticas en los órganos linfoides. 12,13,14 Con los estudios histopatológicos de los órganos linfoides secundarios podría determinarse los posibles mecanismos patogénicos, pero la realización de este tipo de exámenes todavía es poco frecuente.…”