Bone marrow transplantation attenuates murine IgA nephropathy: Role of a stem cell disorder

Background. The pathogenesis of IgA nephropathy is still obscure. The aim o f this study was to investigate whether the fundamental pathogenesis of IgA nephropathy lies in bone marrow stem cells (BMCs). Methods. We used donors of two different strains for bone marrow transplant ation (BMT) into mice with a high content of serum IgA (ddY strain, HIGA mi ce), a murine model of IgA nephropathy. One group (B6-->HIGA, N = 5) receiv ed BMCs of C57BL/6j (B6) mice, and the other (HIGA-->HIGA, N = 8) were reco nstituted with BMCs of HIGA mice. Results. Twenty-six weeks after BMT, in B6-->HIGA mice, mesangial deposits of IgA and C3 were statistically milder than those in HIGA-->HIGA mice. Lig ht microscopic observations disclosed that glomerular sclerosis and mesangi al matrix expansion in B6-->HIGA mice were decreased compared with those in HIGA-->HIGA mice. These B6-->HIGA mice also excreted less urinary albumin than HIGA-->HIGA mice. Furthermore, serum levels of IgA in B6-->HIGA mice w ere markedly lower than those in HIGA-->HIGA mice. Size analysis of serum I gA revealed that macromolecular IgA were notably lower in B6-->HIGA mice th an in HIGA-->HIGA mice. Conclusions. Our results suggest that qualitative and quantitative changes of serum IgA are determined at the level of stem cells, and that BMT from n ormal donors can attenuate glomerular lesions in HIGA mice. This approach m ay offer a new avenue to study the pathogenesis of IgA nephropathy.