Oral bacteria induce IgA autoantibodies against a mesangial protein in IgA nephropathy model mice.

Mizuki Higashiyama, Kei Haniuda, Yoshihito Nihei, Saiko Kazuno, Mika Kikkawa, Yoshiki Miura, Yusuke Suzuki, Daisuke Kitamura

Life science alliance 2024 Apr

filter terms:

IgA nephropathy (IgAN) is caused by deposition of IgA in the glomerular mesangium. The mechanism of selective deposition and production of IgA is unclear; however, we recently identified the involvement of IgA autoantibodies. Here, we show that CBX3 is another self-antigen for IgA in gddY mice, a spontaneous IgAN model, and in IgAN patients. A recombinant antibody derived from gddY mice bound to CBX3 expressed on the mesangial cell surface in vitro and to glomeruli in vivo. An elemental diet and antibiotic treatment decreased the levels of autoantibodies and IgAN symptoms in gddY mice. Serum IgA and the recombinant antibody from gddY mice also bound to oral bacteria of the mice and binding was competed with CBX3. One species of oral bacteria was markedly decreased in elemental diet-fed gddY mice and induced anti-CBX3 antibody in normal mice upon immunization. These data suggest that particular oral bacteria generate immune responses to produce IgA that cross-reacts with mesangial cells to initiate IgAN. © 2024 Higashiyama et al.

Citation

Mizuki Higashiyama, Kei Haniuda, Yoshihito Nihei, Saiko Kazuno, Mika Kikkawa, Yoshiki Miura, Yusuke Suzuki, Daisuke Kitamura. Oral bacteria induce IgA autoantibodies against a mesangial protein in IgA nephropathy model mice. Life science alliance. 2024 Apr;7(4)