MECHANISM OF INFILTRATION AND ACTIVATION OF GLOMERULAR MONOCYTES MACROPHAGES IN IGA NEPHROPATHY/

Glomerular deposits of fibrin-related antigens (FRA), C3c, membrane at tack complex (MAC) were examined by the immunoperoxidase method on 176 renal biopsy specimens from 120 cases with IgA nephropathy including 56 cases with sequential biopsies. On 47 sets of repeated renal biopsy specimens, the glomerular infiltration. of the following immune cells was examined by the indirect immunoperoxidase method; immune cells po sitive for C3bi receptor (C3biR; CR3/CD11b, CR4/CD11c), HLADR antigen and several leukocyte surface markers (CD45R, CD3, CD15 and CD68). Twe nty-four-hour urine protein (UP) at the renal biopsy was also evaluate d. The glomerular deposition of FRA was inversely correlated with C3c/ MAC deposition (p < 0.00001). Most cases (163 of 176) were classified into the following two types; type C with dominant deposition of C3c ( 97 cases) and type F with dominant deposition of FRA (66 cases), excep t for 13 cases with equivalent deposits of C3c and FRA (7 cases, type B) and without C3 or FRA deposits (6 cases, type O). In 56 rebiopsied cases, apparent conversion from type F or C into the other was observe d only in one case though a few cases in type C lost or reduced C3c de position to an equivocal type at the follow-up biopsy, which were incl uded in type C', an expanded category of type C. In the whole cases, t he glomerular infiltration of immune cells was significantly correlate d with FRA deposition (p < 0.0002) but not with C3c. Glomerular CD11c cells were significantly correlated with C3c deposition in type C' (p < 0.0001), but not in type F. Glomerular HLADR positive immune cells were significantly correlated with glomerular CD3+ T cells in type F ( p < 0.001), but not in type C'. In type C', UP was significantly corre lated with glomerular CD11c+ cells (p < 0.0001) but not with CD15+ or HLADR+ cells. On the other hand, in type F, UP was significantly corre lated with CD15+ and HLADR+ cells (p < 0.001) but not with CD11c+ cell s. These results suggested that there are multiple pathways in inducin g glomerular infiltration of immune cells in IgA nephropathy. In type C, local activation of complements might primarily induce immune cell infiltration through C3biR and these C3biR+ cells are involved in indu cing proteinuria. On the other hand, in type F, in which complement ac tivation is weak, immune cells might infiltrate directly through their Fc receptor or MHC class II antigens, and might be activated by T-cel l/macrophage interaction to induce proteinuria.