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

Abstract

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.

Autoantibodies and neurodegeneration in multiple sclerosis

“…They are implicated in several autoimmune diseases such as autoimmune arthritis, type 1 diabetes mellitus, atherosclerosis, and MS. 80 The concentration of antia-crystalline antibodies in sera of MS patients correlates with activity as well as severity of the disease. 30 In CSF, IgG antibodies to small HSPs (eg HSP27, lA crystallin and lB crystalline) are not increased, but to HSP70 and HSC70 (heat shock cognate protein 70) are elevated and correlate with the disease course. 31 Increased antibody titers to HSP60 are present in CSF of both patients with MS and with OND.…”

Multiple Sclerosis

“…15,16 Antibodies that bind to other antigens such as alpha-B-crystallin, alu repeats, myelin basic protein, and myelin-associated glycoprotein have been reported but not rigorously studied. [17][18][19][20] Despite several published attempts to detect and quantify antibodies directed against Lemus et al myelin and nonmyelin antigens in patients with MS, there is no consensus. This lack of a self-directed immune response producing antibodies argues against the hypothesis of MS as an autoimmune disease ( Fig.…”

“…Other viral agents like varicella zoster and rubella are considered as possible risk factors but not causal agents. 40,41 Of note, vitamin D Table 1 Revised criteria for a disease to be considered autoimmune: neuromyelitis optica and multiple sclerosis Criteria for Autoimmune Disease 7 NMO MS Immune response to a precise autoantigen in all patients aquaporin 4 22,23 Multiple antigens have been described, not present in all patients 12,13,[17][18][19][20] Lesion reproducibility after administration of autoantibody or T cells Exacerbation of EAE model after adoptive transfer of neuromyelitis optica Abs 27…”

Body fluid biomarkers in multiple sclerosis: how far we have come and how they could affect the clinic now and in the future

“…AlphaB-crystallin is a small heat-shock protein found to be increased in brains with demyelination, and elevated levels of antibodies against this protein were detected in serum and CSF of MS patients [238]. Although autoantibodies against AlphaB-crystallin were also observed in patients with OND, approximately 60% of MS patients are positive [238]. In addition, AlphaB-crystallin was increased in the CSF in 100% of MS patients and in approximately 90% of OND patients [239].…”