Eomesodermin expression in CD4+T‐cells associated with disease progression in amyotrophic lateral sclerosis

Abstract Aim To clarify the role of Eomesodermin (EOMES) to serve as a disease‐relevant biomarker and the intracellular molecules underlying the immunophenotype shifting of CD4 + T subsets in amyotrophic lateral sclerosis (ALS). Methods The derivation and validation cohorts included a total of 148 ALS patients and 101 healthy controls (HCs). Clinical data and peripheral blood were collected. T‐cell subsets and the EOMES expression were quantified using multicolor flow cytometry. Serum neurofilament light chain (NFL) was measured. In 1‐year longitudinal follow‐ups, the ALSFRS‐R scores and primary endpoint events were further recorded in the ALS patients of the validation cohort. Results In the derivation cohort, the CD4 + EOMES + T‐cell subsets were significantly increased ( p < 0.001). EOMES + subset was positively correlated with increased serum NFL levels in patients with onset longer than 12 months. In the validation cohort, the elevated CD4 + EOMES + T‐cell proportions and their association with NFL levels were also identified. The longitudinal study revealed that ALS patients with higher EOMES expression were associated with higher progression rates ( p = .010) and worse prognosis ( p = .003). Conclusions We demonstrated that increased CD4 + EOMES + T‐cell subsets in ALS were associated with disease progression and poor prognosis. Identifying these associations may contribute to a better understanding of the immunopathological mechanism of ALS.