Multiple sclerosis patients show sexual dimorphism in cytokine responses to myelin antigens.
Multiple sclerosis affects more women than men. The reasons for this are unknown. Previously, we have shown significant differences in women versus men in inflammatory cytokine responses to the major protein component of myelin, proteolipid protein (PLP), which is thought to be a target in MS patients. Here, using the ELISPOT assay, we examined sex differences in single-cell secretion of Th1 and Th2 cytokines from freshly isolated PBMC between relapsing remitting (RR) MS patients and healthy individuals. Cells were stimulated with MS-associated antigens including proteolipid protein (PLP), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and non-disease related antigens. Our data show a sex bias in the cytokine responses to multiple MS-relevant myelin antigens: Women with MS show IFNgamma-skewed responses and men with MS show IL-5-skewed responses. These data extend our previous findings [Pelfrey, C.M., Cotleur, A.C., Lee, J.C., Rudick, R.A. 2002. Sex differences in cytokine responses to myelin peptides in multiple sclerosis. J. Neuroimmunol. 130, 211-223.]: (1) by demonstrating gender skewing in cytokine responses to an expanded myelin antigen repertoire, which includes MBP, MOG and PLP; (2) by showing TNFalpha and IL-10 do not display comparable gender skewing compared to IFNgamma and IL5; (3) by defining the patient population as early, untreated RRMS patients to avoid confounding factors, such as different disease stages/disability and immunomodulatory therapy; and (4) by showing HLA type does not appear to underlie the gender differences. These findings may explain increased susceptibility to MS in women and could contribute to the differences in disease severity between men and women.
Moldovan
Ioana R
IR
Department of Neurosciences, NC30, Cleveland Clinic Lerner Research Institute, 9500 Euclid Ave., Cleveland, OH 44195, United States.
Cotleur
Anne C
AC
Zamor
Natacha
N
Butler
Robert S
RS
Pelfrey
Clara M
CM
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins / Q000276:immunology*; D018991:Myelin Proteolipid Protein / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D012727:Sex Characteristics; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D006684:HLA-DR Antigens; D015848:Interleukin-5; C571326:MOG protein, human; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D007371:Interferon-gamma