ABSTRACT Aim 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. Methods 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. Results 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. Conclusion 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.
Kim et al. (Wed,) studied this question.