Reduced peripheral CD4+ memory T-cell counts mark a mortality-associated immunophenotype in anti-MDA5 dermatomyositis.

BACKGROUND: Anti-MDA5 dermatomyositis is often complicated by interstitial lung disease and early mortality. Peripheral lymphopenia has been linked to poor outcomes, but the routinely measured lymphocyte compartments underlying this signal remain incompletely defined. We used hierarchical flow-cytometric immunophenotyping to characterize the mortality-associated lymphopenic pattern. METHODS: In this exploratory retrospective cohort, we studied 64 adults with anti-MDA5 dermatomyositis who had baseline lymphocyte subset testing and 180-day follow-up. We compared major lymphocyte populations and T-cell differentiation subsets between survivors and non-survivors. Associations with mortality were assessed using ROC, Kaplan-Meier, and Cox regression analyses. RESULTS: Thirteen of 64 patients died by day 180. Non-survivors showed T-cell-dominant lymphopenia, most marked in CD4+ central and effector memory T cells. Median-split Kaplan-Meier analysis showed lower 180-day survival with lower CD4+ memory T-cell counts (log-rank P = 0.00058). Each 1-SD increase in CD4+ memory T-cell count was associated with lower mortality after age adjustment (aHR 0.16, 95% CI 0.04-0.63, P = 0.008). CD4+ memory T-cell count had an AUC of 0.80 (95% CI 0.68-0.91), comparable to total CD4+ T-cell count (AUC 0.78, 95% CI 0.65-0.90). Findings were similar after separate adjustment for LDH or KL-6 and among patients with baseline RP-ILD. CONCLUSIONS: Reduced peripheral CD4+ memory T-cell counts characterized a T-cell-dominant immunophenotype associated with 180-day mortality in anti-MDA5 dermatomyositis. These exploratory findings refine the established CD4+ lymphopenia signal and require validation in independent cohorts.