Imasawa Toshiyuki, Utsunomiya Yasunori
Department of Internal Medicine, Division of Nephrology and Hypertension, Jikei University School of Medicine, Tokyo, Japan.
Exp Nephrol. 2002;10(1):51-8. doi: 10.1159/000049898.
The pathogenesis of IgA nephropathy (IgAN) is still obscure. In this study, we investigated whether the fundamental pathogenesis of IgAN lies in bone marrow stem cells (BMCs) and whether bone marrow transplantation from normal C57BL/6j (B6) mice can attenuate glomerular lesions in a murine IgAN model (high serum level IgA ddY mouse; HIGA mouse). Mesangial deposits of IgA and C3 and glomerular sclerosis in HIGA recipients of BMCs from B6 mice (B6-->HIGA) were decreased as compared with those in HIGA recipients of BMCs from HIGA mice (HIGA-->HIGA). Furthermore, the serum levels of IgA and macromolecular IgA were notably lower in B6-->HIGA mice than in HIGA-->HIGA mice. Of note, bone marrow derived H-2(b)-positive cells from B6 donors were observed in the glomeruli of H-2(b)-negative HIGA recipients. Our data suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells and that bone marrow transplantation from normal mice may not only replace recipients' immune cells with donors' BMCs, but also regenerate glomerular cells in HIGA mice. This approach offers a promising strategy for the treatment of IgAN.
IgA肾病（IgAN）的发病机制仍不清楚。在本研究中，我们调查了IgAN的根本发病机制是否在于骨髓干细胞（BMCs），以及来自正常C57BL/6j（B6）小鼠的骨髓移植是否能减轻小鼠IgAN模型（高血清IgA水平ddY小鼠；HIGA小鼠）中的肾小球病变。与接受来自HIGA小鼠的BMCs的HIGA受体（HIGA→HIGA）相比，接受来自B6小鼠的BMCs的HIGA受体（B6→HIGA）中IgA和C3的系膜沉积以及肾小球硬化减少。此外，B6→HIGA小鼠的血清IgA和大分子IgA水平明显低于HIGA→HIGA小鼠。值得注意的是，在H-2(b)阴性的HIGA受体的肾小球中观察到来自B6供体的骨髓来源的H-2(b)阳性细胞。我们的数据表明，血清IgA的质和量的变化在干细胞水平上被决定，并且来自正常小鼠的骨髓移植不仅可以用供体的BMCs替代受体的免疫细胞，还可以使HIGA小鼠的肾小球细胞再生。这种方法为IgAN的治疗提供了一种有前景的策略。
