Anti-superoxide dismutase antibodies are associated with survival in patients with sporadic amyotrophic later sclerosis

Marka Van Blitterswijk, Sunita Gulati, Elizabeth Smoot, Matthew Jaffa, Nancy Maher, Bradley T. Hyman, Adrian J. Ivinson, Clemens R. Scherzer, David A. Schoenfeld, Merit E. Cudkowicz, Robert H. Brown, Daryl A. Bosco

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14 Scopus citations

Abstract

Our objective was to test the hypothesis that aberrantly modified forms of superoxide dismutase (SOD1) influence the disease course for sporadic amyotrophic lateral sclerosis (SALS). We probed for anti-SOD1 antibodies (IgM and IgG) against both the normal and aberrantly oxidized-SOD1 (SODox) antigens in sera from patients with SALS, subjects diagnosed with other neurological disorders and healthy individuals, and correlated the levels of these antibodies to disease duration and/or severity. Anti-SOD1 antibodies were detected in all cohorts; however, a subset of ∼510% of SALS cases exhibited elevated levels of anti-SOD1 antibodies. Those SALS cases with relatively high levels of IgM antibodies against SODox exhibit a longer survival of 6.4 years, compared to subjects lacking these antibodies. By contrast, SALS subjects expressing higher levels of IgG antibodies reactive for the normal WT-SOD1 antigen exhibit a shorter survival of 4.1 years. Anti-SOD1 antibody levels did not correlate with disease severity in either the Alzheimer's or Parkinson's disease cohorts. In conclusion, the association of longer survival with elevated levels of anti-SODox antibodies suggests that these antibodies may be protective. By extension, these data implicate aberrantly modified forms of WT-SOD1 (e.g. oxidized SOD1) in SALS pathogenesis. In contrast, an immune response against the normal WT-SOD1 appears to be disadvantageous in SALS, possibly because the anti-oxidizing activity of normal WT-SOD1 is beneficial to SALS individuals.

Original languageEnglish (US)
Pages (from-to)430-438
Number of pages9
JournalAmyotrophic Lateral Sclerosis
Volume12
Issue number6
DOIs
StatePublished - Nov 1 2011

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Keywords

  • Sporadic amyotrophic lateral sclerosis
  • alzheimer's disease
  • immunotherapy
  • parkinson's disease
  • superoxide dismutase

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Van Blitterswijk, M., Gulati, S., Smoot, E., Jaffa, M., Maher, N., Hyman, B. T., Ivinson, A. J., Scherzer, C. R., Schoenfeld, D. A., Cudkowicz, M. E., Brown, R. H., & Bosco, D. A. (2011). Anti-superoxide dismutase antibodies are associated with survival in patients with sporadic amyotrophic later sclerosis. Amyotrophic Lateral Sclerosis, 12(6), 430-438. https://doi.org/10.3109/17482968.2011.585163