Elevated Interleukin-21 expression is correlated with systemic sclerosis' severity in Tunisian patients

Systemic sclerosis (SSc), a rare and lethal autoimmune disorder where patients presents diverse clinical features, therefore unravelling a potential biomarker within a specific cohort is crucial for improving patient care, especially for rare diseases. This study sought to identify potential biomarkers in Tunisian SSc patients. Gene expression analysis of interleukins (IL)-21 and IL-22 in peripheral blood mononuclear cells, using quantitative real-time polymerase chain reaction (qrt-pcr), revealed upregulated IL-21 and downregulated IL-22 in SSc patients compared to healthy controls. Notably, IL-21 overexpression in patients correlated with pulmonary complications, a severe SSc manifestation. Interestingly, flow cytometry analysis displayed no difference in Th17 cells between groups, suggesting that Th17 might not be the primary drivers of cytokine dysregulation. The hypothesis was supported by qRT-PCR, which analysed two key genes: IL-17A and RORγt. Finally, we examined RNA sequencing data to further validate our hypothesis. Collectively, our study provides novel insights into the cytokine landscape of SSc in Tunisian patients, highlighting a dysregulation in IL-21 and IL-22 expression, and suggesting that IL-21 could be a potential biomarker of severity.