Divergent proviral load trajectories and clonal dynamics of HTLV-1-infected cells during antirheumatic therapy in rheumatoid arthritis

Abstract

The optimal management of human T-cell leukemia virus type 1 (HTLV-1) carriers requiring long-term immunomodulatory therapy remains unclear. Patients with rheumatoid arthritis (RA) living with HTLV-1 frequently receive antirheumatic therapy, raising concerns regarding the potential risk of adult T-cell leukemia/lymphoma (ATL) development. In this multicenter longitudinal cohort study, we analyzed HTLV-1-positive patients with RA enrolled in a Japanese registry. Patients were followed for 5 years while receiving antirheumatic therapy. Serial HTLV-1 proviral load (PVL) measurements, HTLV-1 Analysis System (HAS)-Flow immunophenotyping, and RAISING-based clonality analyses were performed. Among 56 patients, PVL remained stable in most cases, whereas approximately one-third showed progressive increases during follow-up. Increasing PVL was associated with expansion of CADM1 + CD7− CD4 + infected T cells. RAISING analyses demonstrated increased clonality and progressive dominance of pre-existing infected-cell clones in a subset of patients with increasing PVL. In contrast, patients with stable PVL largely maintained polyclonal infected-cell populations. Clonal expansion showed little temporal association with treatment modification. In HTLV-1-infected patients receiving antirheumatic therapy, PVL increases may reflect selective expansion of pre-existing infected T-cell clones in a subset of patients rather than direct pharmacologic effects. Longitudinal monitoring of infected-cell dynamics may help identify clonal evolution associated with increased ATL risk during immunomodulatory therapy.