Circulating Th1/17 cells serve as a biomarker of disease severity and a target for early intervention in AChR-MG patients.

Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered to be critical regulators of thymic inflammation in AChR-MG patients. However, Th17 cells are functionally heterogeneous and circulating Th17 subsets are incompletely understood in AChR-MG patients. Here, we studied characteristics of Th17 subsets in peripheral blood from treatment-naïve AChR-MG patients, patients treated with immunosuppressants, as well as healthy controls. We found increased frequencies of circulating Th1-like Th17 (Th1/17) (IFN-γ + IL-17 + CD4 + CD3+) cells, which declined earlier than conventional Th17 (IFN-γ - IL-17 + CD4 + CD3+) cells in patients who respond well to immunosuppression treatment. Additionally, circulating Th1/17 cell frequencies were found to correlate positively with disease severity. Further, compared to conventional Th17 cells, Th1/17 cells showed an elevated expression of IFNG, TBX21, IL23R, CSF2, and a reduced expression of AHR and IL10. Taken together, our results suggest circulating Th1/17 cells may serve as a biomarker of disease severity and provide a strong rationale for early intervention in AChR-MG patients.