Elevated circulating interleukin-17 levels in systemic sclerosis: a meta-analysis

The aim of this meta-analysis was to evaluate the association between circulating interleukin-17 (IL-17) levels and systemic sclerosis (SSc).

We conducted a comprehensive systematic search in MEDLINE, Embase, and Web of Science for relevant studies. The meta-analysis compared serum/plasma IL-17, IL-17A, IL-17B, IL-17E, and IL-17F levels in SSc patients with those in control subjects, incorporating subgroup analyses based on ethnicity and disease subtype.

This analysis included 16 studies, comprising 1,229 patients diagnosed with SSc and 839 control participants. The meta-analysis did not identify a significant difference in circulating IL-17 levels between SSc patients and controls in overall group (standardized mean difference [SMD]=0.260; 95% confidence interval [CI]=-1.805 to 2.336; p=0.825). However, recent studies supported this finding, demonstrating a stronger association (SMD=2.040; 95% CI=1.049 to 3.030; p<0.001). IL-17A levels were significantly higher in SSc patients (SMD=2.046; 95% CI=0.724 to 3.369; p=0.002), along with notable increases in IL-17B (SMD=0.764; 95% CI=0.230 to 1.298; p=0.005), IL-17E (SMD=0.672; 95% CI=0.282 to 1.062; p=0.001), and IL-17F (SMD=0.402; 95% CI=0.019 to 0.784; p=0.039). However, no significant difference in IL-17A levels was observed between diffuse and limited SSc groups.

IL-17A, IL-17B, IL-17E, and IL-17F were significantly elevated in SSc, with IL-17A demonstrating the most pronounced association. These findings suggest that specific IL-17 subtypes, particularly IL-17A, play a role in SSc pathogenesis.