B Cell Activating Factor Does Not Play a Pivotal Role in the Synthesis of Aberrantly Glycosylated IgA

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, yet its pathogenesis remains incompletely understood. B cell activating factor (BAFF), a TNF family member involved in B cell activation and IgA class switching, has been proposed as a potential pathogenic factor in IgAN. However, its role in disease progression is unclear. This study aimed to investigate the pathological role of BAFF in IgAN using grouped ddY (gddY) mice, a spontaneous murine model of IgAN.

gddY mice were treated with anti-BAFF monoclonal antibody (anti-BAFF Ab) or PBS via intraperitoneal injection twice a week for 4 weeks. Urinary albumin, serum immunoglobulins, and IgA-IgG immune complex were measured pre- and post-treatment. Serum levels of aberrantly glycosylated IgA were quantified using specific lectin-based assays. Glomerular IgA and C3 depositions were evaluated by immunofluorescence, and B cell populations in spleen and bone marrow were analysed by flowcytometry.

Anti-BAFF Ab treatment significantly reduced serum IgA, IgG, and IgM levels as compared with PBS treatment (p < 0.001, p = 0.003, and p = 0.002, respectively). However, it did not affect serum aberrantly glycosylated IgA, IgA-IgG immune complex, and urinary albumin excretion. Glomerular depositions of IgA and C3 as well as B cell population in the spleen and bone marrow were also not affected by anti-BAFF Ab treatment.

BAFF inhibition reduces general immunoglobulin levels but does not impact nephritogenic IgA production or disease progression in murine IgAN. These findings suggest that BAFF-dependent IgA production may not be involved in the pathogenesis of IgAN.