Serum IgA and the Production of IgA by Peripheral Blood and Bone Marrow Lymphocytes in Patients With Primary IgA Nephropathy: Evidence for the Bone Marrow as the Source of Mesangial IgA

The origin of the mesangial IgA1 in primary IgA nephropathy (IgAN) is unknown. The bone marrow, the prime production site of plasma IgA in healthy humans, has not been previously investigated in patients with IgAN. In patients with IgAN, we found an increased percentage of IgA plasma cells containing IgA1 in the bone marrow (89.7% ± 2.6% v 84.3% ± 6.6%, P = 0.01), an increased percentage of serum IgA as IgA1(92.2% ± 4.9% v 80.2% ± 6.6%, P < 0.001), and an increased percentage of IgA1 of the IgA produced by peripheral blood lymphocytes in culture (75% ± 16% v 54% ± 19%, P < 0.01). These findings are compatible with the bone marrow as production site of the mesangial IgA1. The data on IgA1 polymers are more difficult to interpret because their role in the pathogenesis of IgAN is still controversial. We found an increased concentration of both polymeric and monomeric IgA1 in the sera and supernatants of cultures of bone marrow of patients, although the ratio of polymeric to total IgA1 remained normal. In our opinion, the mucosa of the digestive tract is an unlikely source of the mesangial IgA because the absence of IgA2 in the deposits contrasts to the high percentage of IgA2 plasma cells in the intestinal mucosae. Moreover, in normal individuals, the digestive mucosae contribute very little to plasma IgA. Although the respiratory tract contains a higher percentage of IgA1 plasma cells, the 25% fraction of IgA plasma cells containing IgA2 is still very substantial. This percentage argues against the respiratory mucosae as a source of the mesangial IgA. We propose that the bone marrow is the site of long-term overproduction of IgA1 antibodies in patients with IgAN. This increased production leads to increased levels of IgA1 in the circulation and secondary deposition in the mesangium.