Deficiency of dimeric IgA₁ in the serum of patients with IgA Nephropathy (IgAN)

IgA nephropathy is the most common primary cause of glomerulonephritis worldwide. Approximately 20-30% of patients develop chronic renal failure, requiring dialysis and/or transplantation. The histological hallmark of the disease is deposition of IgA1 (including dimers) in the mesangium of the kidney. Total IgA in the serum is also increased in about half of the patients and increased levels of large IgA-containing complexes have also been described in IgAN sera. In order to elucidate the relationship between abnormalities in circulating IgA and the renal pathology, we have compared the distribution of molecular size forms of IgA1 in the sera of patients with IgAN with those from normal controls. Total IgA1 was first isolated using jacalin-agarose chromatography. The eluted IgA was subjected to HPLC molecular sieve chromatography (Pharmacia HR200). The relative proportion of monomeric, dimer, and polymeric IgA1 were calculated from the HPLC chromatograms. The results are shown below: Monomeric Dimeric Polymeric (*mean ± 1 S.D.) IgAN patients (n=16) *79.6 ± 5.5 7.8 ± 2.3 12.6 ± 5.7 Normal controls (n=14) 76.7 ± 6.1 13.9 ± 5.3 9.5 ± 3.4 P values 0.19 0.001 0.092 The proportion of IgA that was monomeric was the same in the sera from the IgAN patients and controls. However, the proportion of dimers in the patient sera was decreased and the proportion of polymers was more variable among the patient sera than among the normal sera. The deficits in dimeric IgA1 may be due to enhanced incorporation into polymeric complexes or disproportionate sequestration in the kidney. Since dimeric has been shown to inhibit activation of some inflammatory cells, the deficit in circulating IgA may allow pathologic activation of mesangial cells in the kidney of patients with IgAN.