Th1 and Th17 Cells and Associated Cytokines Discriminate among Clinically Isolated Syndrome and Multiple Sclerosis Phenotypes

Abstract

Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system. It is a heterogeneous pathology that can follow different clinical courses, and the mechanisms that underlie the progression of the immune response across MS subtypes remain incompletely understood. Here, we aimed to determine differences in the immunological status among different MS clinical subtypes. Blood samples from untreated patients diagnosed with clinically isolated syndrome (CIS) (n = 21), different clinical forms of MS (n = 62) [relapsing–remitting (RRMS), secondary progressive, and primary progressive], and healthy controls (HCs) (n = 17) were tested for plasma levels of interferon (IFN)-γ, IL-10, TGF-β, IL-17A, and IL-17F by immunoanalysis. Th1 and Th17 lymphocyte frequencies were determined by flow cytometry. Our results showed that IFN-γ levels and the IFN-γ/IL-10 ratio were higher in CIS patients than in RRMS patients and HC. Th1 cell frequencies were higher in CIS and RRMS than in progressive MS, and RRMS had a higher Th17 frequency than CIS. The Th1/Th17 cell ratio was skewed toward Th1 in CIS compared to MS phenotypes and HC. Receiver operating characteristic statistical analysis determined that IFN-γ, the IFN-γ/IL-10 ratio, Th1 cell frequency, and the Th1/Th17 cell ratio discriminated among CIS and MS subtypes. A subanalysis among patients expressing high IL-17F levels showed that IL-17F and the IFN-γ/IL-17F ratio discriminated between disease subtypes. Overall, our data showed that CIS and MS phenotypes displayed distinct Th1- and Th17-related cytokines and cell profiles and that these immune parameters discriminated between clinical forms. Upon validation, these parameters might be useful as biomarkers to predict disease progression.

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin

“…Indeed, a significantly increased ratio of DEGs in the pathogenesis of multiple sclerosis pathway was appreciated. Lending support to our findings, multiple sclerosis is an autoimmune demyelinating disease that is associated with alterations in Th1/Th2/Th17 cells . From our results, we hypothesized that similar to the immune clearance that tempers the oncogenic transformation of premalignant, senescent hepatocytes, somatic mutations in neoplastic melanocytes can lead to the expression of antigens which stimulate immune system activation and clearance.…”

Differential Expression of SMAD Genes and S1PR1 on Circulating CD4+ T Cells in Multiple Sclerosis and Crohn’s Disease

“…Finally, we investigated the expression of Th17 genes. It is known that IL17F levels are higher in RRMS patients than in healthy donors and that these levels can discriminate between different phenotypes of MS [46]. However, in our cohorts, no differences were found for IL17A or IL17F, probably owing to the low expression level observed in our samples.…”

Effects of Pregnancy and Hormones on T cell Immune Regulation in Multiple Sclerosis

“…For example, IL-12, a heterodimer between IL-12A and IL-12B, is essential for the development of IFN-γ-producing TH1 cells and IL-12B is also part of IL-23 that is necessary for TH17 development. However, the relative importance of TH1 versus TH17 in the MS pathogenesis remains unclear, and the importance of the different subsets could vary across individuals as well as from disease initiation to relapse and disease progression (Arellano et al 2017, Frisullo et al 2008. The importance of the different TH subsets is further complicated as for example TH cells expressing both IFN-γ and IL-17 have been identified in patients with MS (Kebir et al 2009) and CCR6 + myelin-reactive CD4 + T cells from patients express higher levels of IFN-γ, IL-17 and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to healthy controls (Cao et al 2015).…”