Higher complement factor H (FH) levels were observed in IgAVN than IgAN, and positive correlation between circulating FH and C3 levels was present in IgAVN.
Our findings suggested that both coding and noncoding variants in CFH acted synergistically to regulate the degree of complement activation and thereby contributed to IgAN susceptibility.
A number of recent studies have now documented elevated levels of some factor H-related proteins in IgA nephropathy, which might contribute to enhanced complement activation.
Atypical Hemolytic Uremic Syndrome Associated with Complement Factor H Mutation and IgA Nephropathy: A Case Report Successfully Treated with Eculizumab.
Large, international, genome-wide association studies have shown that deletion of complement factor H-related genes 1 and 3 (<i>CFHR3,1Δ</i>) is associated with a reduced risk of developing IgAN, although the prognostic value of these deletions in IgAN remains unknown.
In this issue, 2 groups report that levels of factor H-related protein 1 are elevated in patients with IgA nephropathy and correlate with disease progression.
As compared to IgAN patients without progressive disease, glomeruli from patients with progressive IgAN had significantly higher abundance of components of the classical and the terminal complement pathways, and inhibitory factors such as Factor H and factor H related proteins.
An intronic variant at the complement factor H (CFH) gene on chromosome 1q32 (rs6677604) associates with risk of IgA nephropathy (IgAN), but the association signal has not been uniformly replicated in Han Chinese populations.
A recent genome-wide association study of IgA nephropathy (IgAN) identified 1q32, which contains multiple complement regulatory genes, including the complement factor H (CFH) gene and the complement factor H-related (CFHRs) genes, as an IgAN susceptibility locus.
Our recent genome-wide association study of IgAN identified susceptibility loci on 1q32 containing the complement regulatory protein-encoding genes CFH and CFHR1-5, with rs6677604 in CFH as the top single-nucleotide polymorphism and CFHR3-1 deletion (CFHR3-1∆) as the top signal for copy number variation.
Mutations in the complement factor H gene (CFH) region associate with renal-limited mesangial proliferative forms of glomerulonephritis including IgA nephropathy (IgAN), dense deposit disease (DDD) and C3 glomerulonephritis (C3GN).
Recent genome-wide association studies (GWAS) have identified multiple susceptibility loci for immunoglobulin A nephropathy (IgAN), the most common form of glomerulonephritis, implicating independent defects in adaptive immunity (three loci on chromosome 6p21 in the MHC region), innate immunity (8p23 DEFA locus, 17p23 TNFSF13 locus, 22q12 HORMAD2 locus), and the alternative complement pathway (1q32 CFH/CFHR locus).
Their findings include the following: (1) partial deficiencies for C2, beta 1H (H), properdin (P), or C4 binding protein (C4BP) in four patients with end-stage renal disease, (2) an association between the C3*F allele with IgA nephropathy in the combined group of unrelated patients from Kentucky and the Mid-South, (3) the occurrence of C4B deficiency in two siblings with IgA nephropathy, and (4) an association between C4A deficiency and poor outcome in patients with IgA nephropathy diagnosed as adults.