Human anti-thrombospondin type 1 domain-containing 7A antibodies induce membranous nephropathy through activation of lectin complement pathway

To investigate whether the human anti-thrombospondin type 1 domain-containing 7A (THSD7A) antibody-induced membranous nephropathy (MN) is mediated by activating lectin complement pathway. Automatic biochemical apparatus was used to assess renal function of mice. The serum levels of anti-THSD7A antibodies and complement were tested by using ELISA. The expression level of THSD7A and mannose-binding lectin (MBL) in clinical tissue, and the histological features of MN in mice were examined by immunochemical methods. We found that THSD7A, MBL, and complement expression level from patients with circulating anti-THSD7A antibodies were significantly higher than that in normal group. Furthermore, difference of renal function in anti-THSD7A antibody-containing serum treatment groups and control groups was significant. Meanwhile, human anti-THSD7A autoantibodies activated the complement system and induced the histological features of MN in mice. In conclusion, human anti-THSD7A antibodies induce MN through activating MBL lectin complement pathway in mice.