Reduced serum BCMA levels distinguish patients with primary antibody deficiency

Abstract

Abstract B-cell maturation antigen (BCMA) is a TNF family receptor that binds a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF). BCMA is expressed by immunoglobulin secreting cells, but not other B cells, and supports their survival. Primary antibody deficiency (PAD) is the most common primary immunodeficiency and may lead to infection and complications including autoimmunity, enteropathy, lung disease, and malignancy. PAD patients with these complications have reduced survival, yet there are no validated tests to predict those at risk. We previously demonstrated that BCMA is present in the serum and its levels are elevated in patients with multiple myeloma. As BCMA is expressed by both normal and malignant antibody-producing cells, we examined serum levels of BCMA in PAD. Patients with PAD (n=68) had markedly reduced BCMA levels (median, 7.30) compared with healthy donors (n=119; median, 35.20; P < 0.0001). When subgrouped based upon PAD diagnosis, serum BCMA was reduced compared to controls among those with common variable immunodeficiency (CVID) (n=48; median, 7.16; P <0.0001) and X-linked agammaglobulinemia (n=8; median, 2.30; P <0.0001), but not among those with selective IgA deficiency or hyper IgM syndrome. CVID patients with any inflammatory complication, or enteropathy specifically, had significantly lower serum BCMA than CVID patients without complications (P < 0.01 for both). Serum BCMA moderately correlated with isotype-switched memory B cells (r = 0.473), but poorly correlated with IgA, IgG, or IgM levels or total B cell levels. These results demonstrate that reduced serum BCMA levels are found in PAD patients, distinguish types of PAD, and are associated with the development of complications in CVID.