CDR3 sequences in IgA nephropathy are shorter and exhibit reduced diversity

Abstract

Immunoglobulin (Ig) A nephropathy (IgAN) is the most common glomerulonephritis, which is characterized by the deposition of IgA antibody in the glomerulus. Systematic dissection of immune composition may contribute to a better understanding of the alternations in the immune system in IgAN. To this end, here we applied immune repertoire sequencing technology for parallel analysis of the complementary determining region 3 (CDR3) of all B cell receptors, including all five antibody subtypes (IgA, IgG, IgM, IgE and IgD), in 13 patients with IgAN and 7 healthy individuals. A significant decrease in CDR3 length was observed in the IgAN group. In particular, the JH6 family was significantly increased in IgAN. Amino acid usage was also altered in IgAN. Shannon, Simpson, Gini and Diversity 50 indices also revealed significant differences in the diversity of IgG, IgM and IgA antibodies as compared with controls. The proportions of IgA and IgG were increased, whereas IgM was decreased in IgAN. Moreover, a greater number of CDR3 sequences was shared between patients with IgAN. These findings suggest that the BCR immune repertoire is dramatically altered in IgAN, as characterized by shortened CDR3 length, as well as decreased overall diversity of CDR3.