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 to have an immunological origin which may involve complement-mediated pathogenic mechanisms. We performed C4 phenotyping and C4 isotype quantification in 93 IgAN patients in Southern Sweden. Phenotype frequencies did not deviate from those of healthy controls. However, three patients had homozygous C4A deficiency and these all belonged to a group of fifteen patients with end-stage renal failure (p < 0.0035). Progression to end-stage renal failure did not appear to be faster than in other IgAN patients. Both C4A and C4B concentrations were raised in the IgAN patients, but the C4A/C4B concentration ratios did not deviate from those of healthy controls. This indicated that heterozygosity for C4A or C4B deficiency or other reasons for the relatively low concentrations of the protein were not associated with disease susceptibility. There was no correlation between low C4A/C4B ratio and poor prognosis. In conclusion, the findings suggested that homozygous C4A deficiency predisposes to development of end-stage renal failure. The question if this is due to complement dysfunction or to linked genetic factors remains to be elucidated.