Spinal cord injury triggers systemic autoimmunity: evidence for chronic B lymphocyte activation and lupus-like autoantibody synthesis.
Clinical and experimental data indicate that spinal cord injury (SCI) elicits pathological T-cell responses. Implicit in these data, but poorly understood, is that B lymphocytes (B cells) also contribute to the delayed pathophysiology of spinal trauma. Here, for the first time, we show that experimental spinal contusion injury elicits chronic systemic and intraspinal B cell activation with the emergence of a B cell-dependent organ-specific and systemic autoimmune response. Specifically, using sera from spinal cord injured mice, immunoblots reveal oligoclonal IgG reactivity against multiple CNS proteins. We also show SCI-induced synthesis of autoantibodies that bind nuclear antigens including DNA and RNA. Elevated levels of anti-DNA antibodies are a distinguishing feature of systemic lupus erythematosus and, via their ability to cross-react with neuronal antigens, can cause neuropathology. We show a similar pathologic potential for the autoantibodies produced after SCI. Thus, mammalian SCI produces marked dysregulation of B cell function (i.e. autoimmunity) with pathological potential.
Ankeny
Daniel P
DP
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University College of Medicine, Columbus, Ohio 43210, USA.
Lucin
Kurt M
KM
Sanders
Virginia M
VM
McGaughy
Violeta M
VM
Popovich
Phillip G
PG
D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology* / Q000503:physiopathology; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology / Q000503:physiopathology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000503:physiopathology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000276:immunology; D015213:Neuroimmunomodulation / Q000276:immunology; D009696:Nucleic Acids / Q000276:immunology; D043025:Oligoclonal Bands / Q000276:immunology; D013119:Spinal Cord Injuries / Q000150:complications / Q000276:immunology* / Q000503:physiopathology
D001323:Autoantibodies; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D009696:Nucleic Acids; D043025:Oligoclonal Bands