Interferon gamma responses to myelin peptides in multiple sclerosis correlate with a new clinical measure of disease progression.
The relationship between autoreactivity to myelin antigens and disease progression in multiple sclerosis (MS) is not fully understood. We addressed this relationship by cross-sectionally comparing an objective measure of MS disability with immune cytokine responses to myelin proteins. The ELISPOT assay was used to determine the ex vivo interferon gamma (IFNgamma) and interleukin-10 (IL-10) production by peripheral blood mononuclear cells (PBMCs) in response to peptides spanning the entire proteolipid protein (PLP) and myelin basic protein (MBP) molecules in 20 patients with relapsing-remitting (RR) MS and 27 age- and sex-matched healthy controls. MS patients showed significantly higher MBP-induced IFNgamma responses and PLP-induced IL-10 responses compared with healthy controls. Using the Multiple Sclerosis Functional Composite (MSFC), a new multifactorial measure of disability, MS patients showed a significant correlation between the IFNgamma response to PLP peptides and MBP peptides, and disability. In contrast, in MS patients, there was no correlation between the MSFC and the response to unrelated control antigens or mitogens. These data show that myelin-specific T lymphocytes secreting the inflammatory cytokine IFNgamma correlate with functional impairment in MS, supporting an antigen-specific link between the immune response to myelin and disability in MS.
Moldovan
Ioana R
IR
Department of Neurosciences, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Rudick
Richard A
RA
Cotleur
Anne C
AC
Born
Sarah E
SE
Lee
Jar-Chi
JC
Karafa
Matthew T
MT
Pelfrey
Clara M
CM
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D004676:Myelin Basic Protein / Q000494:pharmacology*; D018991:Myelin Proteolipid Protein / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D016207:Cytokines; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D016753:Interleukin-10; D007371:Interferon-gamma