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Enolase and Arrestin are Novel Nonmyelin Autoantigens in Multiple Sclerosis

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Introduction: 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.

Methods: 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, β-arrestin, and myelin basic protein were determined.

Results: MS patients had a greater prevalence of positive T-cell proliferative responses to NSE, retinal arrestin, and β-arrestin than healthy controls (p<0.0001). The proliferative response against NSE, retinal arrestin, and β-arrestin correlated with the response against myelin basic protein (p≤0.004). Furthermore, the proliferative response against retinal arrestin was correlated to β-arrestin (p<0.0001), whereas there was no such correlation between non-neuronal enolase and NSE (p = 0.23).

Discussion: 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 β-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.

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ACKNOWLEDGMENTS

This research was supported by a grant from the MS Scientific Foundation of Canada to FF and POC, a grant form the Canadian Institutes of Health Research to HMD, and grants from the National Eye Institute and the Karl Kirchgessner Foundation to WCS.

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Authors and Affiliations

  1. Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada

    Farzin Forooghian

  2. Institute of Medical Science, University of Toronto, Toronto, Canada

    Farzin Forooghian & Hans-Michael Dosch

  3. Department of Immunology, University of Toronto, Toronto, Canada

    Roy K. Cheung & Hans-Michael Dosch

  4. Department of Ophthalmology, University of Florida, Gainesville, USA

    W. Clay Smith

  5. Department of Neurology, University of Toronto, Toronto, Canada

    Paul O’connor

  6. Hospital for Sick Children, Room 10128, Elm Wing, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Farzin Forooghian

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Forooghian, F., Cheung, R.K., Smith, W.C. et al. Enolase and Arrestin are Novel Nonmyelin Autoantigens in Multiple Sclerosis. J Clin Immunol 27, 388–396 (2007). https://doi.org/10.1007/s10875-007-9091-1

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