Possible role of autoantibodies against nephrin in an experimental model of chronic graft-versus-host disease

Abstract

SummaryNephrin, a product of the NPHS1 gene, is a component of the slit diaphragms that are found between glomerular foot processes and is a crucial element for glomerular filtration barrier. Recently, nephrin has been focused in a number of studies of proteinuria development including various types of acquired glomerular diseases including minimal change nephrotic syndrome and membranous nephropathy. However, the precise role of nephrin in such acquired glomerular diseases is still unknown. To analyse the role of nephrin further, two kinds of anti-nephrin antibodies were raised in the rabbits and applied to an experimental mouse model of chronic graft-versus -host disease, in which (C57BL/10 ¥ ¥ ¥ ¥ DBA/2) F1 mice developed clinically apparent severe proteinuria with significant glomerular lesions 7 weeks after parental DBA/2 cell transfer. Antibody-sandwich ELISA detected anti-nephrin antibodies during week 2 to week 6, with the peak at week 2 or week 4. Colocalization of nephrin and IgG on week 4, week 6, and week 8 was revealed by confocal microscopic analysis, suggesting that in situ immune complex formation with nephrin in glomerular lesion. Taken together, it seems to be suggested nephrin and its autoantibody have a certain role in the development of glomerular lesion in our model mice.

Renal pathology in hematopoietic cell transplantation recipients

“…35 Others demonstrated the development of anti-nephrin autoantibodies and mesangioproliferative glomerulonephritis in a mouse model of chronic graftversus-host disease after non-myeloablative transplantation. 36 Small studies have separately characterized efficacy of the anti-CD20 agent rituximab in treatment of chronic graft-versus-host disease, 37 and idiopathic membranous glomerulonephritis. [38][39][40][41] Thus, it is not unexpected that rituximab-treated hematopoietic cell transplantation recipients with biopsy proven membranous glomerulonephritis responded well (three allogeneic and one autologous transplant).…”

Podocyte Antigens and Glomerular Disease

“…Podocyte-associated proteins might serve as targets for the circulating alloimmune antibodies that are directed against a podocyte antigen expressed in the recipient but absent from the donor, or against an allovariant. Autoantibodies against nephrin were produced in an experimental model [24] . The possible connection between fetal cell microchimerism (i.e.…”

Focal segmental glomerulosclerosis as a complication of graft-versus-host disease

“…Antibodies against nephrin, the slit diaphragm protein, have been observed in patients with congenital nephrotic syndrome of the Finnish type who developed recurrent nephrotic syndrome in renal grafts after transplantation. 3 nagahama et al 4 detected anti bodies against nephrin in the sera derived from mouse models of chronic GVHD-which is characterized by a condition similar to systemic lupus erythematosus with severe immune complex glomerulonephritis-before and during proteinuria development. Co-localization of igG and nephrin was seen, which suggested in situ immune complex formation.…”