Aberrant expression of triggering receptor expressed on myeloid cell-1 is involved in the immunopathological mechanism of myasthenia gravis

Triggering receptor expressed on myeloid cells-1 (TREM-1) and TREM-2, cell surface receptors involved in innate and adaptive immunity, exist in soluble (sTREM-1 and sTREM-2) and membrane-bound forms, with the soluble form serve as biomarkers in many immune diseases. However, the role of TREM-1 and TREM-2 in myasthenia gravis (MG) remains unclear. This study aims to investigate the expression of TREM-1 and TREM-2 in MG, as well as their potential role in the immunopathological mechanism of MG. We enrolled a total of 85 MG patients and 43 healthy controls (HC). Enzyme-linked immunosorbent assay and flow cytometry were used to quantify the expression of TREM-1 and TREM-2 in MG patients and HC. The levels of TREM-1 and TREM-2 mRNA of peripheral blood mononuclear cells were measured by reverse transcription quantitative real-time polymerase chain reaction (RT‒qPCR) in MG and HC. <i>In vitro</i> experiments were performed to explore the functional effects of intervening TREM-1 on CD4⁺T cells. We found that serum sTREM-1 levels were significantly elevated in MG patients Compared to HC, whereas sTREM-2 showed no difference. Additionally, sTREM-1 levels in MG patients positively correlated with disease severity and memory B-cell proportions. TREM-1 expression was reduced and most significantly on CD4⁺T and CD8⁺T cells in MG patients. Inhibition of TREM-1 inhibited Treg cell differentiation but had no significant effect on Th1, Th2, and Th17, indicating its pathogenic role in MG.