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Correlation of Blood T Cell and Antibody Reactivity to Myelin Proteins with HLA Type and Lesion Localization in Multiple Sclerosis¹

Neuroimmunology Research Unit, School of Medicine, University of Queensland, Royal Brisbane and Women’s Hospital, Herston, Brisbane, Queensland, Australia

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS. The numbers of autoimmune T cells and Abs specific for proteins of CNS myelin are increased in the blood in some patients with MS. The aim of this study was to investigate whether there are correlations between the specificity of the autoimmune responses in the blood, the HLA molecules carried by the patient, and the clinical features of MS, because studies on experimental autoimmune encephalomyelitis, an animal model of MS, indicate that autoimmune responses targeting particular myelin proteins and the genetic background of the animal play a role in determining the pattern of lesion distribution. We tested blood T cell immunoreactivity to myelin proteins in 100 MS patients, 70 healthy controls, and 48 patients with other neurological disorders. Forty MS patients had strongly increased T cell reactivity to one or more myelin Ags. In these 40 patients, the most robust correlation was between CD4⁺ T cell reactivity to myelin proteolipid protein residues 184–209 (PLP_184–209) and development of lesions in the brainstem and cerebellum. Furthermore, carriage of HLA-DR4, -DR7, or -DR13 molecules by MS patients correlated with increased blood T cell immunoreactivity to PLP_184–209, as well as the development of lesions in the brainstem and cerebellum. Levels of PLP_190–209-specific Abs in the blood also correlated with the presence of cerebellar lesions. These findings show that circulating T cells and Abs reactive against specific myelin Ags can correlate with lesion distribution in MS and suggest that they are of pathogenic relevance.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grant RG 3190-A-1 from the National Multiple Sclerosis Society and funding from Multiple Sclerosis Australia.

² Address correspondence and reprint requests to Dr. Judith Greer, Neuroimmunology Research Unit, School of Medicine, University of Queensland, Clinical Sciences Building, Royal Brisbane and Women’s Hospital, Herston, Brisbane, Queensland 4029, Australia. E-mail address: j.greer{at}uq.edu.au

³ Abbreviations used in this paper: MS, multiple sclerosis; CND, patients with other CNS disorders; CSF, cerebrospinal fluid; EAE, experimental autoimmune encephalomyelitis; EDSS, Kurtzke Expanded Disability Status Scale; MBP, myelin basic protein; MOBP, myelin oligodendrocyte basic protein; MOG, myelin oligodendrocyte glycoprotein; MRI, magnetic resonance imaging; MSSS, MS severity score; OSP, oligodendrocyte-specific protein; PLP, myelin proteolipid protein; SI, stimulation index.

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The JI 2008 180: 5759-5760. [Full Text]