Histone‐Specific CD4⁺ T Cell Plasticity in Active and Quiescent Systemic Lupus Erythematosus

Abstract

ObjectiveTo assess whether circulating histone‐specific T‐cells represent tools for precision medicine in systemic lupus erythematosus (SLE)MethodsSeroprevalence of autoantibodies and human leukocyte antigen (HLA)‐DRB1 profile were assessed among 185 patients with SLE and combined with bioinformatics and literature evidence to identify HLA‐peptide autoepitope couples for ex vivo detection of antigen‐specific T‐cells through flow cytometry. T‐cell differentiation and polarisation was investigated in subjects with SLE, Takayasu's arteritis and healthy controls (HC) carrying HLA‐DRB1*03:01 and/or 11:01. SLE disease activity index 2000 (SLEDAI‐2K) and Lupus low disease activity state (LLDAS) were used to estimate disease activity and remission.ResultsHistone‐specific CD4+ T‐cells were selectively detected in patients with SLE. Among patients with a history of anti‐DNA antibodies, 77% had detectable histone‐specific T‐cells while 50% had lymphocytes releasing cytokines or upregulating activation markers after in vitro challenge with histone peptide antigens. Histone‐specific regulatory and effector Th1‐, Th2‐, Th1*‐polarised cells were significantly more abundant in SLE patients with quiescent disease. In contrast, total Th1‐, Th2‐, Th1*‐polarised and regulatory T‐cells were similarly represented between patients and controls or SLE patients with active vs quiescent disease. Histone‐specific effector memory T‐cells accumulated in the blood of patients with quiescent SLE, while total effector memory T‐cell counts did not change. Immunosuppressants were associated with expanded CD4+ histone‐specific naïve and terminally differentiated T‐cells.ConclusionHistone‐specific T‐cells are selectively detected in patients with SLE and their concentration in the blood varies with disease activity, suggesting that they represent innovative tools for patient stratification and therapy.image