In IgAN, complement system has attracted great attention. In patients with IgAN, except for the characteristic IgA deposition, C3 Selleck Palbociclib is the most commonly co-deposited molecule, approximately affects 90% patients. Serological complement activation was also found in IgAN. Additionally, the elevated urine factor H level in patients

with IgAN was reported in recent study. Accumulating evidences from plasma, urine and renal biopsy samples suggested the involvement of factor H and complement activation in IgAN pathogenesis. CFH, CFHR3 and CFHR1 are regulators of complement system, which is a key system for immune surveillance and homeostasis. In

systemic autoimmune diseases, such as SLE, activation of the complement system is involved in pathogenesis. In recent years, following the identification of aberrant glycosylated IgA1 and anti-glycan antibodies in patients with IgAN, it have been convinced that IgAN is an autoimmune disease, in which IgA1-containing immune complexes were the initiator MAPK Inhibitor Library for glomerular injury. In our recent study, we enrolled two populations, Beijing Discovery Cohort of IgAN-GWAS and Beijing Follow-up Cohort, to explore the genetic mechanism of variants in CFH, CFHR3 and CFHR1 on IgAN. In the Beijing Discovery Cohort, we found the top

SNP rs6677604 was associated with glomerular mesangial C3 deposition by genotype-phenotype correlation analysis. In the Beijing Follow-up Cohort, after the confirmation of tight linkage between rs6677604-A and CFHR3-1Δ, we found rs6677604-A was associated with higher factor H levels and lower complement activation split product C3a, which implied less system complement activation. Furthermore, factor H levels were positively associated with circulating C3 levels and negatively associated with mesangial C3 deposition, indicated the important role of factor H in controlling complement activation in IgAN. Besides rs6677604, serum IgA levels and galactose deficient IgA1 levels, GPX6 which were pathogenic initiator of IgA nephropathy, were also found to be associated with mesangial C3 deposition in IgAN. Our findings, together with our present understanding of IgAN pathogenesis, suggested that variants in CFH, CFHR3 and CFHR1 regulated pathogenic IgA1 induced system complement activation due to its effect on factor H levels, which might influence circulating IgA1-containing immune complex formation and the following mesangium deposition, and at last contributed to IgAN susceptibility.