Correlation of blood T cell and antibody reactivity to myelin proteins with HLA type and lesion localization in multiple sclerosis

Greer, Judith M., Csurhes, Peter A., Muller, Diane M. and Pender, Michael P. (2008) Correlation of blood T cell and antibody reactivity to myelin proteins with HLA type and lesion localization in multiple sclerosis. Journal of Immunology, 180 9: 6402-6410. doi:10.4049/jimmunol.180.9.6402


Author Greer, Judith M.
Csurhes, Peter A.
Muller, Diane M.
Pender, Michael P.
Title Correlation of blood T cell and antibody reactivity to myelin proteins with HLA type and lesion localization in multiple sclerosis
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2008-05-01
Year available 2008
Sub-type Article (original research)
DOI 10.4049/jimmunol.180.9.6402
Open Access Status Not yet assessed
Volume 180
Issue 9
Start page 6402
End page 6410
Total pages 9
Editor R. Rich
M. Hogan
Place of publication Bethesda, U.S.A.
Publisher American Association of Immunologists
Language eng
Subject C1
920111 Nervous System and Disorders
920108 Immune System and Allergy
110703 Autoimmunity
110903 Central Nervous System
1103 Clinical Sciences
1109 Neurosciences
Abstract 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 (PLP184–209) 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 PLP184–209, as well as the development of lesions in the brainstem and cerebellum. Levels of PLP190–209-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.
Keyword Experimental autoimmune encephalomyelitis
Oligodenrocyte-specific protein
Central nervous system
Brain stem
Encephalitogenic epitope
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Thu, 09 Apr 2009, 09:51:46 EST by Carmen Buttery on behalf of UQ Centre for Clinical Research