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

作者：van Blitterswijk Marka; Gulati Sunita; Smoot Elizabeth; Jaffa Matthew; Maher Nancy; Hyman Bradley T; Ivinson Adrian J; Scherzer Clemens R; Schoenfeld David A; Cudkowicz Merit E; Brown Robert H Jr; Bosco Daryl A^*

来源：Amyotrophic Lateral Sclerosis, 2011, 12(6): 430-438.

DOI：10.3109/17482968.2011.585163

• Sporadic amyotrophic lateral sclerosis
• superoxide dismutase
• immunotherapy
• Parkinson's disease
• Alzheimer's disease

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 similar to 5-10% 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.

• 出版日期2011-11