Altered B-cell populations in IgA nephropathy

B-cells are centrally implicated in the pathogenesis of IgA nephropathy (IgAN) as the source of galactose-deficient IgA1 and autoantibodies against it. Nevertheless, little is known about the B-cell compartment in IgAN. We aimed to compare the frequencies of major peripheral blood B-cell subsets in patients with IgAN and healthy controls (HC) to identify novel B-cell signatures of disease. Peripheral blood mononuclear cells were isolated by density gradient centrifugation. B-cell phenotype was determined by flow cytometry (Navios EX, Beckman Coulter) using monoclonal antibodies against CD19, CD1d, CD24, CD27, CD38, CD43, IgD, and IgA. Serum IgA, IgG, IgM and IgE were measured by nephelometry (Atellica NEPH 630 System, Siemens). The frequency of B-1-like cells (CD27+CD43+) was significantly reduced in patients with IgAN compared to HC. We observed a correlation between renal function and B-1-like cell frequency in patients with IgAN. The frequencies of naïve B-cells, double negative, switched and unswitched memory B-cell populations were comparable in IgAN patients and HC. In IgAN patients B-1-like cells inversely correlated with renal IgA deposits and total serum IgA, but not with IgM, IgG or IgE. We found that up to 25% of CD27+CD43+ B-cells had undergone class-switching to IgA, and that the frequency of IgA+ cells among B-1-like lymphocytes was higher in IgAN patients than in HC. There is a significant decrease of B-1-like cells in the peripheral blood of IgAN patients. Serum IgA and renal impairment correlate with reduction in B-1-like cell frequency. B-1-like cells have been implicated in the production of IgA, and their presence at mucosal sites has been associated with the pathogenesis of IgAN. Therefore, it is conceivable that in IgAN patients B-1-like cells migrate to mucosal sites where they initiate IgA production and thus contribute to renal decline.