Cross-reactive myelin antibody induces renal pathology.
Experimental autoimmune encephalomyelitis (EAE) is an autoimmune model for multiple sclerosis (MS). Previously, we reported renal immunoglobulin (Ig) deposition in mice with myelin oligodendrocyte glycoprotein (MOG(92-106))-induced progressive EAE and naive mice injected with MOG(92-106) hybridoma cells producing antibody that cross-reacts with various autoantigens including double-stranded DNA. To assess whether MOG(92-106) antibodies actually induce kidney changes, the extent of renal Ig deposition and changes in glomerular histology and filtration were investigated. Mice with progressive EAE exhibited Ig deposition, glomerular hypercellularity and proteinuria indicating kidney dysfunction. MOG(92-106) hybridoma cell injected mice also had Ig deposition and proteinuria. Therefore, sensitization with MOG(92-106) and transfer of MOG(92-106) antibodies can induce both central nervous system and renal pathology. The renal involvement reported in MS is believed to occur as a side effect of nephrotoxic drugs or neurogenic bladder. Our results demonstrate that an autoimmune response against myelin could induce pathologic changes in the kidney and may help explain renal changes reported in patients with progressive MS.
Peterson
Lisa K
LK
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Masaki
Takahisa
T
Wheelwright
Steven R
SR
Tsunoda
Ikuo
I
Fujinami
Robert S
RS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D003429:Cross Reactions; D004247:DNA / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006825:Hybridomas; D007136:Immunoglobulins / Q000032:analysis / Q000276:immunology; D007668:Kidney / Q000166:cytology / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D011507:Proteinuria
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D007136:Immunoglobulins; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D004247:DNA