Oral administration of dimeric monoclonal IgA antibody as a candidate therapeutic approach for spontaneous colitis in mice.

Recent large-scale studies have shown dysbiosis in patients with IBD compared with healthy controls. How to modulate microbiota is a key issue to prevent or treat IBD. We focus the intestinal IgA as a good candidate for microbiota modulators due to its antigen-specificity, which may allow IgA to distinguish colitogenic from symbiotic bacteria. We have isolated a W27 monoclonal dimeric IgA derived from IgA-producing cell of wild-type intestinal lamina propria, as it showed the high-affinity to a variety of bacterial strains but low-reactivity to beneficial bacteria such as Bifidobacterium bifidum and Lactobacillus casei. Here we show that the oral treatment of W27 IgA can prevent spontaneous colitis observed in AID mutant mice that produce only low-affinity IgA due to somatic hypermutation defect. The oral W27 treatment increased Clostridiales and Erysipelotrichales in feces and colonic regulatory T cells. It also normalized immune hyperactivation status and colonic crypt structure in AID mutant mice. Oral monoclonal W27 IgA treatment is thus a potential therapeutic for IBD through modulating microbiota to symbiosis.