Enolase and arrestin are novel nonmyelin autoantigens in multiple sclerosis

• Published in: Journal of clinical immunology Vol. 27; no. 4; pp. 388 - 396
• Main Authors: Forooghian, Farzin, Cheung, Roy K, Smith, W Clay, O'Connor, Paul, Dosch, Hans-Michael
• Format: Journal Article
• Language: English
• Published: Netherlands Springer Nature B.V 01.07.2007
• Subjects: Adult; Amino Acid Sequence; Antigens; Arrestin; Arrestin - immunology; Arrestin - pharmacology; Autoantibodies; Autoantigens; Autoantigens - immunology; Autoantigens - pharmacology; Autoimmune diseases; Autoimmunity; Cell Proliferation - drug effects; Cells, Cultured; Dose-Response Relationship, Immunologic; Female; Humans; Immunodominant Epitopes; Lymphocyte Activation - drug effects; Lymphocytes T; Male; Molecular Sequence Data; Multiple sclerosis; Multiple Sclerosis - immunology; Myelin; Myelin basic protein; Myelination; Neurodegeneration; Pathogenesis; Phosphopyruvate hydratase; Phosphopyruvate Hydratase - immunology; Phosphopyruvate Hydratase - pharmacology; Reference Values; Retina; Sequence Alignment; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Uveitis
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-007-9091-1

Although myelin autoimmunity is known to be a major factor in the pathogenesis of multiple sclerosis (MS), the role of nonmyelin antigens is less clear. Given the complexity of this disease, it is possible that autoimmunity against nonmyelin antigens also has a pathogenic role. Autoantibodies against enolase and arrestin have previously been reported in MS patients. The T-cell response to these antigens, however, has not been established. Thirty-five patients with MS were recruited, along with thirty-five healthy controls. T-cell proliferative responses against non-neuronal enolase, neuron-specific enolase (NSE), retinal arrestin, beta-arrestin, and myelin basic protein were determined. MS patients had a greater prevalence of positive T-cell proliferative responses to NSE, retinal arrestin, and beta-arrestin than healthy controls (p<0.0001). The proliferative response against NSE, retinal arrestin, and beta-arrestin correlated with the response against myelin basic protein (p < or = 0.004). Furthermore, the proliferative response against retinal arrestin was correlated to beta-arrestin (p<0.0001), whereas there was no such correlation between non-neuronal enolase and NSE (p = 0.23). There is accumulating evidence to suggest that the pathogenesis of MS involves more than just myelin autoimmunity/destruction. Autoimmunity against nonmyelin antigens may be a component of this myriad of immunopathological events. NSE, retinal arrestin, and beta-arrestin are novel nonmyelin autoantigens that deserve further investigation in this respect. Autoimmunity against these antigens may be linked to neurodegeneration, defective remyelination, and predisposition to uveitis in multiple sclerosis. Further investigation of the role of these antigens in MS is warranted.