High prevalence of anti-alpha-crystallin antibodies in multiple sclerosis: correlation with severity and activity of disease.
BACKGROUND
The presence of T-cell reactivity to alphaB-crystallin in patients with multiple sclerosis (MS) has suggested that this small molecular weight heat shock protein (Hsp) may be an autoantigen in MS.


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 alphaB-crystallin, to the homologous chaperone protein, alphaA-crystallin, and to another small Hsp, Hsp 27.


RESULTS
Sixty-three percent of MS patients exhibited immunoreactivity to alpha-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-alpha-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-alpha-crystallin reactivity. The concentration of anti-alpha-crystallin antibodies in patients with MS correlated with severe disease (P<0.05) and with active disease (P<0.025).


CONCLUSIONS
Our observations support the notion that anti-alpha-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.
Agius
M A
MA
University of California at Davis, 95616, USA.
Kirvan
C A
CA
Schafer
A L
AL
Gudipati
E
E
Zhu
S
S
D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D003459:Crystallins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D012008:Recurrence; D012697:Serine Endopeptidases; D016036:Seroepidemiologic Studies; D012720:Severity of Illness Index
D001323:Autoantibodies; D001324:Autoantigens; D003459:Crystallins; D000939:Epitopes; D006360:Heat-Shock Proteins; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase