Effect of gender on T-cell proliferative responses to myelin proteolipid protein antigens in patients with multiple sclerosis and controls

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system. Gender influences both susceptibility to MS, with the disease being more common in women, and the clinical course of disease, with an increased proportion of males developing the primary progressive form of the disease. The basis for these differences may include genetic and immunological factors, and the immunological differences between men and women may be influenced by the effects of the sex hormones. Over several years we have collected blood from MS patients and controls, and measured T-cell responses to myelin proteolipid protein (PLP) and myelin basic protein (MBP) and have shown increased responses to PLP in MS patients compared to healthy controls and patients with other neurological diseases. In the present study we analyzed data from over 500 individuals, to determine whether there are differences between males and females in their responses to PLP and MBP. We found that there was higher frequency of increased T-cell reactivity to immunodominant PLP peptides in women than in men, particularly in non-MS individuals. We suggest that this may be relevant to the higher prevalence of MS in women.

Multiple sclerosis patients show sexual dimorphism in cytokine responses to myelin antigens

“…Our data agree, since neither anti-CD3 nor PHA was able to distinguish sex differences with any of the cytokines we tested, although ratios of IFNγ/IL-5 did reveal some skewing with mitogenic stimulation, but only in women with MS. In another study, women were more likely than men to have increased T-cell reactivity to immunodominant PLP peptides , but did not show increased responses to MBP or MBP 82−100 (Greer et al, 2004). We also were unable to show significant female IFNγ reactivity to MBP or MBP 87−106.…”

“…Notably, 75% of the MS patients in our study were women. One other group has observed a sex bias in the cytokine responses among MS patients (Greer et al, 2004). The common feature between these studies that relates to sex differences in cytokine expression is the use of myelin peptides rather than mitogen stimulation.…”

Sex affects immunity

“…Females with MS exhibit stronger T cell responses to myelin antigens [113], and increased PBMC cytokine production in response to myelin antigen stimulation [114]. Differences in the gene expression profiles in the PBMCs of males and females with MS have been reported [115].…”

Sex Differences in Resting-State Functional Connectivity in Multiple Sclerosis

“…[4][5][6][7] The underlying processes thought to be involved in the development and progression of MS demonstrate significant sex differences. For example, male and female patients with MS have shown differences in the markers of autoimmune function, [8][9][10] and there has been extensive research on the effects of sex hormones on disease progression, particularly during and after pregnancy. 11,12 There is evidence that fluctuations in hormone levels can affect tissue damage in the brain 13 ; these observations have prompted research on the use of sex hormones as a treatment for MS. 14,15 It is unclear, however, whether there are sex differences in conventional MR imaging measures of disease status.…”