Low levels of spontaneously activated peripheral IgA-secreting cells in nontransplanted IgA nephropathy patients

The pathognomonic presence of IgA in the glomerular mesangium of patients with IgA nephropathy (IgAN) suggests an abnormal control of IgA metabolism in this disease that could be modified in transplanted IgAN patients. Alterations of IgA production have been demonstrated in both bone marrow samples and mucosaeassociated tissues from IgAN patients, but the analysis of IgA production by peripheral B lymphocytes in culture has yielded conflicting results, some investigators showing an enhanced secretion of IgA and others reporting similar data as with control samples. Little is known about the endogenous activation state of B cells in IgAN, which can be approached by analyzing peripheral Ig-producing cells, a number of which are recirculating between lymphoid organs. In the present study, two methods were applied to appreciate the numbers of spontaneously activated peripheral B cells. The ELISPOT method provided information about short-term secretion of Igs. Intracytoplasmic immunofluorescence for IgA allowed to identify IgA-containing cells, either as short-rimmed immunocytes or as brightly stained immunoblasts with an enlarged cytoplasm. These cells were enumerated in IgAN patients (n = 31), transplanted IgAN patients (n = 27), control patients with other biopsy-proven renal diseases (nontransplanted, n = 48; transplanted, n = 38), and in healthy individuals (n = 18). The number of IgA spot-forming cells obtained in the control groups (1,251 ± 95 cells/10 6 lymphocytes [mean ±se]) was consistent with those in similar previously reported studies, but differed significantly ( P = 0.01) from those observed in nontransplanted IgAN patients, who had a surprisingly lower number of such cells (699 ± 97 cells/10 6 lymphocytes); the number of IgA spot-forming cells in the transplanted IgAN patients (1,355 ± 182 cells/10 6 lymphocytes) did not differ from that in the control groups. The same pattern was seen for IgA-containing immunoblasts. There was no difference in IgG (overall, 214 ± 13 cells/10 6 lymphocytes) and IgM (overall, 61 ± 10 cells/10 6 lymphocytes) spot-forming cell numbers between the five groups of individuals tested, suggesting that the anomaly noted in IgAN patients was not related to technical problems and that this could be a new feature of this renal disease. The normal levels of spontaneously activated peripheral IgA-producing cells found in transplanted IgAN patients suggest that immunosuppressive treatments could interfere with the anomalies o