Lupus & antiphospholipid syndrome

Transcriptomic effects of hydroxychloroquine in CD4+ T cells from patients with systemic lupus erythematosus: An exploratory pilot study

LupusPublished exploratory pilot study

Authors' conclusion

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.

Study context

Population
Systemic lupus erythematosus (SLE) patients before and 3 months after initiating HCQ therapy, stratified into an induction phase (early, treatment-naïve disease) and a maintenance phase (long-standing disease with concomitant treatments)SLE patients with CD4+ T cells sequenced, independent validation cohort n = 10
Participants
5 patients
Comparison
Before and 3 months after initiating HCQ therapy; induction phase vs maintenance phase
Methodological detailspre- and post-treatment RNA sequencing analysis, validation at the protein level using an immunoassay
  • Pre- and post-treatment RNA sequencing analysis
  • Validation at the protein level using an immunoassay

Primary result

As reported in the abstract

Differentially expressed genes (fold change ≥2, nominal raw p < 0.05) · 3 months

Induction phase

56 genes were upregulated and 193 genes were downregulated

Maintenance phase

71 upregulated and 46 downregulated DEGs

Further findings

Direction of gene regulation between the two phases (chi-square test)

Statistically significant difference, suggesting a predominant gene downregulation in the early phase

GO and KEGG pathway analyses (adj. p < 0.05)

Alterations in "Cytokine-cytokine receptor interaction" and "SLE" pathways

Serum IFN-γ and IL-10 levels in an independent cohort

Significant decreases following HCQ treatment

Original publication

Transcriptomic effects of hydroxychloroquine in CD4+ T cells from patients with systemic lupus erythematosus: An exploratory pilot study. Lupus. Published 2 November 2026. doi:10.1177/09612033261505701

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