Evidence suggesting the involvement of hematopoietic stem cells in the pathogenesis of IgA nephropathy.
To investigate the role of hematopoietic stem cells in the pathogenesis of IgA nephropathy, T-cell-depleted bone marrow cells for 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 for 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.
Imasawa
T
T
Department of Microbiology, Jikei University School of Medicine, Tokyo, Japan. Imayan@jikei.ac.jp
Utsunomiya
Y
Y
Kawamura
T
T
Nagasawa
R
R
Maruyama
N
N
Sakai
O
O
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology; D002678:Chimera / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005920:Glomerular Mesangium / Q000276:immunology / Q000473:pathology; D005922:Glomerulonephritis, IGA / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D008212:Lymphocyte Depletion; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D007070:Immunoglobulin A; D046911:Macromolecular Substances