Evidence Suggesting the Involvement of Hematopoietic Stem Cells in the Pathogenesis of IgA Nephropathy

Abstract To investigate the role of hematopoietic stem cells in the pathogenesis of IgA nephropathy, T-cell-depleted bone marrow cells from IgA nephropathy-prone ddY mice were transplanted into C57BL/6j (B6) mice pretreated with cyclophosphamide. In the 12th week after bone marrow transplantation, 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 significantly more intense than those in B6 mice receiving syngeneic bone marrow cells of B6 mice ([B6→B6]). The serum IgA level in [ddY→B6] mice was higher than that in [B6→B6] mice. Molecular profile analysis of serum IgA revealed that the serum concentration of macromolecular IgA was increased in [ddY→B6], but not in [B6→B6] mice. These data suggest that disorders programmed at the level of BMCs are involved in the pathogenesis of IgA nephropathy by increasing circulating levels of macromolecular IgA.