IDENTIFICATION OF CYTOKINE PATTERNS AND GENE EXPRESSION ASSOCIATED WITH THE REDUCTION OF THE BACILLARY INDEX DURING MULTIDRUG THERAPY IN PATIENTS WITH POLAR LEPROMATOUS LEPROSY

In lepromatous (LL) leprosy, impaired cell-mediated immunity favors intracellular bacillary persistence and multiplication. Although multidrug therapy (MDT) is effective, treatment response varies, and not all patients achieve reduction in bacillary index (BI) after the 12 dose regimen. Elucidating the immunological mechanisms associated with BI reduction may provide insights into mechanisms underlying disease control. This study investigated gene expression patterns and cytokine profiles and cellular phenotypes before and after MDT in LL patients according to BI reduction and their association with treatment response. Whole-blood culture supernatants, sera, and skin lesion samples were collected before and after MDT and stratified according to BI reduction. Patients with ≥1-log reduction in BI were classified as responders (R), whereas those with no or <1 log reduction were classified as non-responders (NR). Gene expression in skin lesions was assessed by RNA-seq and RT-PCR, cellular phenotypes by immunohistochemistry (IHC), and cytokine levels in serum and whole-blood culture supernatants by ELISA. RNA-seq identified significant downregulation of 102 genes after MDT, including genes associated with CXCL10, the IFN pathway, and lipid metabolism. Skin lesions showed reduced expression of macrophage markers, IFN-γ, and CXCL10 after MDT. Serum CXCL10 levels decreased after MDT in NR patients, whereas CXCL10 increased in whole-blood culture supernatants from R patients. The study was approved by the Research Ethics Committee (approval no. 2.450.910). These findings identify immune-related genes and pathways associated with BI reduction following MDT and support CXCL10 as a potential biomarker for monitoring treatment response and disease control in LL leprosy. Further characterization of these immune signatures may contribute to understanding the mechanisms underlying differential responses to MDT and may provide a basis for better treatment response monitoring.