EVIDENCE SUGGESTING THE INVOLVEMENT OF HEMATOPOIETIC STEM-CELLS IN THE PATHOGENESIS OF IGA NEPHROPATHY

To investigate the role of hematopoietic stem cells in the pathogenesi s of IgA nephropathy, T-cell-depleted bone marrow cells hom IgA nephro pathy-prone ddY mice were transplanted into C57BL/6j (B6) mice pretrea ted with cyclophosphamide. In the 12th week after bone marrow transpla ntation, transplanted bone marrow cells had successfully regenerated. In B6 recipients of T-cell-depleted allogeneic bone marrow cells from ddY mice ([ddY-->B6]), mesangial IgA and C3 deposits were significantl y more intense than those in B6 mice receiving syngeneic bone marrow c ells of B6 mice ([B6-->B6]). The serum IgA level in [ddY-->B6] mice wa s higher than that in [B6-->B6] mice. Molecular profile analysis of se rum IgA revealed that the serum concentration of macromolecular IgA wa s increased in [ddY-->B6], but not in [B6-->B6] mice. These data sugge st that disorders programmed at the level of BMCs are involved in the pathogenesis of IgA nephropathy by increasing circulating levels of ma cromolecular IgA. (C) 1998 Academic Press.