Cross-reactive myelin antibody induces renal pathology

Abstract

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 naïve 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.

• Autoantibodies
• autoimmunity
• CNS-demyelinating autoimmune disease
• kidney disease

Acknowledgements

The authors would like to thank Jane E. Libbey, MS and Nikki J. Kirkman, BS, for many helpful discussions and Yukio Saijo, PhD, Kenneth E. Hill, BS, Faris Hasanovic, J. Wes Peterson, Bryan A. Moore, Victor Gappmeier and Daniel G. Smith for excellent technical assistance. We are grateful to Ms. Kathleen Borick for preparation of the manuscript. This work was supported by NIH grant 5R01NS040350.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.