High prevalence of anti-α-crystallin antibodies in multiple sclerosis: Correlation with severity and activity of disease

Introduction - The presence of T-cell reactivity to αB-crystallin in patients with multiple sclerosis (MS) has suggested that this small molecular weight heat shock protein (Hsp) may be an autoantigen in MS. Material and methods - We have tested the serum of patients with clinically definite MS (n=30), other inflammatory neurological disease (n=22), non-inflammatory neurological disease (n=42) and healthy individuals (n=23) for systemic humoral responses to bovine αB-crystallin, to the homologous chaperone protein, αA-crystallin, and to another small Hsp, Hsp 27. Results - Sixty- three percent of MS patients exhibited immunoreactivity to α-crystallin and this was present in all 4 of 4 non-ambulatory patients with MS. In contrast, serum concentrations in MS patients of antibodies to the small Hsp, Hsp27, and to myelin basic protein were negligible (P<0.001). Serum anti-α- crystallin immune responses were detected in significantly lower percentages of patients with other inflammatory neurological diseases (32%, P<0.025), and with non-inflammatory neurological diseases (12%, P<0.001). None of the healthy control individuals showed anti-α-crystallin reactivity. The concentration of anti-α-crystallin antibodies in patients with MS correlated with severe disease (P<0.05) and with active disease (P<0.025). Conclusion - Our observations support the notion that anti-α-crystallin autoimmune responses may contribute to pathogenicity in MS and may represent a mechanism of how recurrent attacks of MS develop subsequent to an isolated demyelinating episode.