C4 PHENOTYPES IN IGA NEPHROPATHY - DISEASE PROGRESSION ASSOCIATED WITH C4A DEFICIENCY BUT NOT WITH C4 ISOTYPE CONCENTRATIONS

IgA nephropathy (IgAN) is a common glomerular disease and is thought t o have an immunological origin which may involve complement-mediated p athogenic mechanisms. We per formed C4 phenotyping and C4 isotype quan tification in 93 IgAN patients in Southern Sweden. Phenotype frequenci es did not deviate from those of healthy controls. However, three pati ents had homozygous C4A deficiency and these all belonged to a group o f fifteen patients with end-stage renal failure (p < 0.0035). Progress ion to end-stage renal failure did not appear to be faster than in oth er IgAN patients. Both C4A and C4B concentrations were raised in the I gAN patients, but the C4A/C4B concentration ratios did not deviate fro m those of healthy controls. This indicated that heterozygosity for C4 A or C4B deficiency or other reasons for the relatively low concentrat ions of the protein were not associated with disease susceptibility. T here was no correlation between low C4A/C4B ratio and poor prognosis. In conclusion, the findings suggested that homozygous C4A deficiency p redisposes to development of end-stage renal failure. The question if this is due to complement dysfunction or to linked genetic factors rem ains to be elucidated.