A potential link between autoimmunity and neurodegeneration in immune-mediated neurological disease

Multiple sclerosis (MS) patients make antibodies to heterogeneous nuclear ribonuclear protein A1 (hnRNP-A1), a nucleocytoplasmic protein. We hypothesized this autoimmune reaction might contribute to neurodegeneration. Antibodies from MS patients reacted with hnRNP-A1-‘M9’, its nuclear translocation sequence. Transfection of anti-M9 antibodies into neurons resulted in neuronal injury and changes in transcripts related to hnRNP-A1 function. Importantly, RNA levels for the spinal paraplegia genes (SPGs) decreased. Changes in SPG RNA levels were confirmed in neurons purified from MS brains. Also, we show molecular interactions between spastin (the encoded protein of SPG4) and hnRNP-A1. These data suggest a link between autoimmunity, clinical phenotype and neurodegeneration in MS.