Increased rates of polymeric IgA synthesis by circulating lymphoid cells in IgA mesangial glomerulonephritis.

Recently we have described the existence of high levels of polymeric IgA, partially as immune complexes, in the serum and kidney from patients with IgA mesangial glomerulonephritis. As these patients often have macroscopic haematuria, following upper respiratory tract infections, our working hypothesis in this paper was that circulating lymphocytes from secretory tissues after viral stimulus could produce in these patients a large amount of polymeric IgA. To test it, peripheral blood lymphocytes (PBL) from patients and controls were cultured for seven days in the presence or absence of pokeweed mitogen (PWM). In cell culture supernatants immunoglobulin synthesis was measured by RIA and the proportion of polymeric and monomeric IgA was determined on Ultrogel Ac A22 column. There was no difference in spontaneous production of immunoglobulins between patients and controls. On the contrary, the IgA synthetized by PWM-stimulated PBL was significantly higher in patients than in controls. The percentages of IgA with molecular weight between 600,000 and 250,000 after supernate fractionation were significantly higher in patients than in controls. The true nature of polymeric IgA was confirmed by their ability to bind secretory component, the existence of covalent structures, and the decrease of the larger forms of IgA after reduction and alkylation. The percentage of IgA producing cells binding secretory component was significantly higher in patients than in controls (69 +/- 21 versus 44 +/- 27) after seven days of culture. IgM and IgG produced in patient culture were similar to controls. These results show that mitogen stimulated PBL from patients with Berger's disease synthetized a large amount of true polymeric IgA. It is suggested that a similar situation could occur in vivo after viral of other stimuli.