High frequencies of circulating Tfh-Th17 cells in myasthenia gravis patients

Abstract

Recent studies show that the frequencies of circulating follicullar helper T (cTfh) cells are significantly higher in myasthenia gravis (MG) patients compared with healthy controls (HC). And, they are positively correlated with levels of serum anti-acetylcholine receptor antibody (anti-AchR Ab). It is unclear whether cTfh cell subset frequencies are altered and what role they play in MG patients. In order to clarify this, we examined the frequencies of cTfh cell counterparts, their subsets, and circulating plasmablasts in MG patients by flow cytometry. We determined the concentrations of serum anti-AChR Ab by enzyme-linked immunosorbent assay (ELISA). We assayed the function of cTfh cell subsets by flow cytometry and real-time polymerase chain reaction (RT-PCR). We found higher frequencies of cTfh cell counterparts, cTfh-Th17 cells, and plasmablasts in MG patients compared with HC. The frequencies of cTfh cell counterparts and cTfh-Th17 cells were positively correlated with the frequencies of plasmablasts and the concentrations of anti-AChR Ab in MG patients. Functional assays showed that activated cTfh-Th17 cells highly expressed key molecular features of Tfh cells including ICOS, PD-1, and IL-21. Results indicate that, just like cTfh cell counterparts, cTfh-Th17 cells may play a role in the immunopathogenesis and the production of anti-AChR Ab of MG.

CD4+ T Cells of Myasthenia Gravis Patients Are Characterized by Increased IL-21, IL-4, and IL-17A Productions and Higher Presence of PD-1 and ICOS

“…The importance of IL-21 in MG has been shown to be associated with activated Tfh1 and Tfh17 cells being their major product (23). High frequencies of cTfh-Th17 cells with increased IL-21 mRNA expression confirmed this finding (36). The present study evaluated both Th-and Tfhrelated cytokines.…”

“…ICOS and PD-1 are two molecules closely related to the function of Tfh cells. Previous studies have reported that ICOS and PD-1 are highly expressed on CD4 + CXCR5 + T cells in the PBMCs of AChR-MG patients (22,23,36). As PD-1 was increased on total CD4 + T cells, covering CD4 + CXCR5 + and CD4 + CXCR5 − T cells, we analyzed ICOS expression also in FIGURE 4 | Increase of PD-1 and ICOS expression on the CD4 + T cells of myasthenia gravis (MG) patients.…”

T Follicular Helper Cells in Autoimmune Disorders

“…Ocular and generalized MG are the two major clinical forms of the disease. Expansion of cTfh cells, concomitant with expansion of circulating plasmablasts, is observed in patients with MG as compared to healthy control subjects, and is associated with the clinical severity and the form of the disease ( 158 – 161 ). Strong correlations between cTfh cells and titers of anti-AChR autoantibodies are frequently described ( 159 – 161 ).…”

“…Expansion of cTfh cells, concomitant with expansion of circulating plasmablasts, is observed in patients with MG as compared to healthy control subjects, and is associated with the clinical severity and the form of the disease ( 158 – 161 ). Strong correlations between cTfh cells and titers of anti-AChR autoantibodies are frequently described ( 159 – 161 ). On the contrary, proportions of Tfr cells are decreased in MG patients as compared to controls, leading to an imbalance in the Tfr/Tfh ratio ( 159 , 162 ).…”

News on the journal Neurological Sciences in 2017

“…Circulating follicullar helper T (cTfh) cells are significantly higher in MG and may play a role in the immunopathogenesis and the production of antiAChR Ab [105]. Tacrolimus is a valid option for the management of MG [106].…”