Bone marrow transplantation attenuates murine IgA nephropathy: role of a stem cell disorder.
BACKGROUND
The pathogenesis of IgA nephropathy is still obscure. The aim of 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 transplantation (BMT) into mice with a high content of serum IgA (ddY strain, HIGA mice), a murine model of IgA nephropathy. One group (B6-->HIGA, N = 5) received BMCs of C57BL/6j (B6) mice, and the other (HIGA-->HIGA, N = 8) were reconstituted 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. Light microscopic observations disclosed that glomerular sclerosis and mesangial 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 were markedly lower than those in HIGA-->HIGA mice. Size analysis of serum IgA revealed that macromolecular IgA were notably lower in B6-->HIGA mice than 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 normal donors can attenuate glomerular lesions in HIGA mice. This approach may offer a new avenue to study the pathogenesis of IgA nephropathy.
Imasawa
T
T
Department of Internal Medicine, Jikei University School of Medicine, Division of Hemodialysis, Saitama, Japan. imayan@jikei.ac.jp
Nagasawa
R
R
Utsunomiya
Y
Y
Kawamura
T
T
Zhong
Y
Y
Makita
N
N
Muso
E
E
Miyawaki
S
S
Maruyama
N
N
Hosoya
T
T
Sakai
O
O
Ohno
T
T
D000367:Age Factors; D000818:Animals; D016026:Bone Marrow Transplantation; D005260:Female; D005922:Glomerulonephritis, IGA / Q000209:etiology / Q000628:therapy*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007070:Immunoglobulin A / Q000097:blood; D051379:Mice
D007070:Immunoglobulin A