Transcriptomic effects of hydroxychloroquine in CD4+ T cells from patients with systemic lupus erythematosus: An exploratory pilot study
Fumito Abe, Masaya Saito, Ayano Saito, Mako Hashimoto, Tatsuro Kanazawa, Takuya Kumagai, Mai Sakaguchi, Futaba Ishii, Hideki Wakui, Naoto TakahashiObjectives
Hydroxychloroquine (HCQ) is a cornerstone of systemic lupus erythematosus (SLE) management, yet its precise molecular impact on CD4+ T cells, particularly regarding disease duration, remains to be fully elucidated. This exploratory study aimed to characterize the two-time-point transcriptomic changes induced by HCQ in CD4+ T cells and explore whether these effects differ between early and established disease phases.
Methods
We performed a pre- and post-treatment RNA sequencing analysis on CD4+ T cells isolated from five SLE patients before and 3 months after initiating HCQ therapy. Patients were stratified into an induction phase (early, treatment-naïve disease) and a maintenance phase (long-standing disease with concomitant treatments). Differentially expressed genes (DEGs) were identified, and key findings were validated at the protein level using an immunoassay.
Results
Despite significant inter-individual heterogeneity, HCQ induced distinct transcriptomic shifts, which were notably more pronounced in induction-phase patients than in maintenance-phase patients. In the induction phase, 56 genes were upregulated and 193 genes were downregulated (fold change ≥2, nominal raw
Conclusions
This exploratory pilot study provides pre- and post-treatment transcriptomic evidence that HCQ exerts multifaceted immunomodulatory effects on CD4+ T cells, suppressing Th1-related, CD40, and histone pathways. These effects appear particularly robust in early-stage SLE, providing a molecular rationale for the clinical benefit of early HCQ introduction.