Highlights d Purification of biologically functional human IGF-1R in fulllength d Cryo-EM structures of insulin or IGF-1 bound human IGF-1R d Hormone induces the formation of active IGF-1R assembly

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IgA 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 CDR3 region of all B cell receptors, including all five antibody subtypes (IgA, IgG, IgM, IgE and IgD), in 13 IgAN patients 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 D50 indices also revealed significant differences in the diversity of IgG, IgM and IgA antibodies as compared to controls. The proportion of IgA and IgG were increased whereas IgM was decreased in IgAN. Moreover, a greater number of CDR3 sequences were shared between IgAN patients. 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.