INTESTINAL B-CELL DEFECTS IN COMMON VARIABLE IMMUNODEFICIENCY

The humoral immune system of the small intestine of 17 patients with c ommon variable immunodeficiency (CVID) was studied by immunohistology using antibodies specific for IgA1,2, IgM, IgG1-4, the J chain and the secretory component (SC). IgA1,2(+), IgG2(+) and IgM(+) lamina propri a B cells were totally lacking in 65% (11/17), 41% (7/17) and 18% (3/1 7) of CVID patients, respectively. One patient exhibited an isolated I gA1 subclass deficiency. The proportion of plasma cells in conventiona lly stained histological sections of the same intestinal biopsies show ed a close correlation with the numbers of IgA(+) and IgM(+) cells. Co nsiderable numbers of J chain-synthesizing cells were present in all p atients 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 immunoglobulin-independent reg ulation of the SC. Clinically, only CVID patients with intestinal IgA defects developed intestinal infections with Giardia lamblia, Campylob acter jejuni or Candida albicans. The outcome of in vitro immunoglobul in 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.