Multiple sclerosis (MS) is a T-cell autoimmune disease of the central nervous system (CNS). Predominance of women in autoimmune diseases suggests that sex hormones may play a role in disease ...susceptibility. A possible role for prolactin, a neuroendocrine peptide with powerful immunomodulatory properties, is suggested in MS. We describe the case of a 32-year-old man affected by relapsing-remitting MS who experienced the first MS clinical event during the development of a prolactin-secreting adenoma and the only two MS relapses during adenoma recurrence. Prolactin may have facilitated the inflammatory process and triggered MS clinical attacks, suggesting a role of prolactin in immunomodulation and therefore in autoimmune disease course.
Abstract Not all patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) develop clinically defined MS (CDMS). At first clinical event we observed increased production ...of IL17, IFNγ and IL10 by peripheral blood mononuclear cells from patients with CIS that remained high in remission. In CD4+ T cells pSTAT3 expression was higher in patients who subsequently converted to CDMS than in patients who did not and controls. The persistency of high levels of pSTAT3 in circulating CD4+ T cells from CIS patients after the first clinical event may favor the early conversion to CDMS.
Coeliac disease (CD) is considered a T cell-mediated autoimmune disease, and up-regulation of T-bet and phosphorylated signal transducers and activators of transcription (pSTAT)1, key transcription ...factors for the development of T helper type 1 (Th1) cells, has been described in the mucosa of patients with untreated CD. Using transcription factor analysis, we investigated whether T-bet and pSTAT1 expressions are up-regulated in the peripheral blood of CD patients and correlate with disease activity. Using flow cytometry, we analysed T-bet, pSTAT1 and pSTAT3 expression in CD4⁺, CD8⁺ T cells, CD19⁺ B cells and monocytes from peripheral blood of 15 untreated and 15 treated CD patients and 30 controls, and longitudinally in five coeliac patients before and after dietary treatment. We evaluated using enzyme-linked immunosorbent assay (ELISA), interferon (FN)-γ, interleukin (IL)-17 and IL-10 production by peripheral blood mononuclear cell (PBMC) cultures. T-bet expression in CD4⁺, CD8⁺ T cells, CD19⁺ B cells and monocytes and IFN-γ production by PBMC was higher in untreated than in treated CD patients and controls. pSTAT1 expression was higher in CD4⁺T cells, B cells and monocytes from untreated than from treated CD patients and controls. pSTAT3 was increased only in monocytes from untreated patients compared with CD-treated patients and controls. The data obtained from the longitudinal evaluation of transcription factors confirmed these results. Flow cytometric analysis of pSTAT1 and T-bet protein expression in peripheral blood mononuclear cells could be useful and sensible markers in the follow-up of CD patients to evaluate disease activity and response to dietary treatment.
The role of leptin was investigated in relapsing–remitting multiple sclerosis (MS). Control and MS patients showed comparable baseline serum leptin levels. During the first year of IFNbeta-1a ...treatment, leptin significantly decreased since 2 months after starting therapy in 11 patients who had no relapses. A significant decrease in IL12/IL10 ratio was observed in this group of patients only after 1 year of treatment. An increase of leptin was observed before the first clinical exacerbation in 13 relapsing patients. Leptin may play a pathogenic role in MS and can be a useful marker of disease activity and response to therapy.
Despite the relatively frequent involvement of the basal ganglia and subthalamic nucleus by multiple sclerosis (MS) plaques, movement disorders (MD), other than tremor secondary to cerebellar or ...brainstem lesions, are uncommon clinical manifestations of MS. MD were present in 12 of 733 patients with MS (1.6%): three patients had parkinsonism, two blepharospasm, five hemifacial spasm, one hemidystonia, and one tourettism. MD in patients with MS are often secondary to demyelinating disease. Also in cases without response to steroid treatment and demyelinating lesions in critical regions, it is not possible to exclude that MD and MS are causally related.
Abstract In pregnant women affected by multiple sclerosis (MS) we observed increased percentages of CD4+ CD25+ Foxp3+ T regulatory cells at the 1st and the 2nd trimester of gestation that was ...associated with a decreased T-bet expression in CD4+ T cells. In women showing clinical relapse and/or new lesions at MRI after delivery we found, a higher expression of T-bet, pSTAT1 and pSTAT3 in CD4+ , CD8+ T cells and CD14+ cells, associated with an increase of IFNγ and IL17 production by PBMC at the 3rd trimester of gestation and after delivery. Our data suggest that the expansion of circulating CD4+ CD25+ Foxp3+ regulatory T cells and the lower expression of T-bet in CD4+ T cells may account for the decreased MS activity during pregnancy. The expression of T-bet, pSTAT1 and pSTAT3 in peripheral blood CD4+ and CD8+ T cells and monocytes could be useful to identify MS patients who will develop a relapse after delivery.
Although interferon (IFN) beta is a widely used disease-modifying therapy in multiple sclerosis (MS), the mechanisms responsible for its effects are not fully understood. Some studies demonstrated ...that IFNbeta induces nerve growth factor (NGF) secretion by astrocytes and by brain endothelial cells. In this study, we determined the production of various neurotrophins (brain-derived neurotrophic factor, BDNF; NGF; glial cell line-derived neurotrophic factor; neurotrophin 3; neurotrophin 4) by peripheral blood mononuclear cells (PBMCs) in relapsing–remitting (RR) and secondary progressive (SP) MS patients during IFNbeta treatment. There were no main variations in neurotrophin production either among all MS patients globally considered or in the group of SPMS subjects. Instead, in the group of RRMS patients who did not present clinical exacerbation of disease up to the end of the study, we found a significant increase in BDNF production as from 6 months after starting therapy.
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