Antibodies to myelin basic protein, myelin oligodendrocytes peptides, α‐β‐crystallin, lymphocyte activation and cytokine production in patients with multiple sclerosis

Vojdani A, Vojdani E, Cooper E (Laboratory of Comparative Neuroimmunology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles; Immunosciences Lab., Inc., Beverly Hills; and University of California Berkeley, Berkeley; CA, USA). Antibodies to myelin basic protein, myelin oligodendrocytes peptides, α‐β‐crystallin, lymphocyte activation and cytokine production in patients with multiple sclerosis. J Intern Med 2003; 254: 363–374. Objective. To measure neurone‐specific humoral and cellular immune parameters in MRI‐positive patients with multiple sclerosis (MS). Background. It has been postulated from animal models for MS and in situ evidence in MS patients that antibodies, activated T cells and proinflam‐ matory cytokines are involved in the destruction of myelin sheaths and loss of oligodendrocytes in active areas. Subjects and methods. Blood samples were obtained from 20 healthy control subjects and 20 patients with abnormal MRI and clinical diagnosis of MS. Sera were tested for levels of IgG, IgM and IgA against myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG) peptides, and a small heat‐shock protein, α‐β‐crystallin. Lympho‐ cytes were isolated and cultured in the presence or absence of MBP, MOG peptides and α‐β‐crystallin, measured for stimulated T cells, cytokine production and compared with controls. Results. Patients with MS showed the highest levels of IgG, IgM or IgA antibodies against one or all three tested antigens. Moreover, in the presence of MBP, MOG peptides or α‐β‐crystallin, a significant percent‐ age of lymphocytes from MS patients underwent blast transformation, which resulted in high levels of interferon γ (IFN‐γ), tumour necrosis factor alpha (TNF‐α) and tumour necrosis factor beta (TNF‐β) production. Sensitivity of these assays was 60–80% and specificity, 65–70%. Conclusions. Detection of antibodies against MBP, MOG peptides, α‐β‐crystallin, lymphocyte stimula‐ tion and production of proinflammatory cytokines in response to these antigens could be used as surrogate markers for the confirmation of MS diagnosis. A combination of antibodies, lymphocyte activation or cytokine production with abnormal MRI may significantly increase the sensitivity and specificity of MS diagnosis.