Factors associated with circulating levels of IL-17A in a high HIV-burden population

BackgroundInterleukin-17A (IL-17A) is a key cytokine in inflammation and autoimmunity. However, its systemic correlates, particularly in a high HIV burden population, are not fully elucidated. This study aimed to identify the sociodemographic, clinical, inflammatory, metabolic, and renal factors independently associated with plasma IL-17A levels. MethodsThis cross-sectional analysis enrolled a cohort of adults from Livingstone Teaching Hospital in Zambia. Sociodemographic and clinical variables were systematically collected. Associations between plasma IL-17A levels and a range of covariates were assessed using simple and multiple linear regression analyses in StatCrunch to identify independent correlates. Statistical significance was set at p<0.05. ResultsA cohort of 366 participants was analyzed, characterized by a predominance of females (70.2%) and people living with HIV (73.5%), the vast majority of whom were receiving integrase strand transfer inhibitors (INSTI)-based antiretroviral therapy. Initial bivariate analysis revealed weak associations between IL-17A and various metabolic and inflammatory markers. In the final multivariable model (Model 1), which included all significant univariate variables, five factors were independently associated with IL-17A: IFN-{gamma} ({beta}: 1.17, 95% CI: 1.01-1.33, p<0.0001), IL-1 ({beta}: 1.60, 95% CI: 0.74-2.47, p=0.0004), IL-5 ({beta}: -0.34, 95% CI: -0.65 - -0.040, p=0.0268), soluble ST2 ({beta}: -26.01, 95% CI: -38.15 - -13.87, p<0.0001), and D-dimer ({beta}: -0.006, 95% CI: -0.009 - -0.002, p=0.0012). Plasma potassium was not significant in this full model ({beta}: 0.78, 95% CI: -3.99-5.56, p=0.744). HIV status was not an independent correlate ({beta}: 95.73, 95% CI: -499.68-691.15, p=0.749). A second model (Model 2) was constructed by adjusting for HIV status only. In this model, plasma potassium was a significant independent correlate of IL-17A ({beta}: 10.07, 95% CI: 4.39-15.76, p=0.0006), along with triglycerides, LDL cholesterol, VLDL, IL-6, TNF-, IL-1, IL-5, soluble ST2, fasting glucose, and lymphocyte count. ConclusionIn a comprehensive model, inflammatory markers (IFN-{gamma}, IL-1, IL-5, sST2) and D-dimer were the independent correlates of IL-17A. The relationship between plasma potassium and IL-17A was context-dependent, significant only in a model excluding other inflammatory cytokines. HIV status was not independently associated with IL-17A when inflammatory markers were considered. These findings highlight complex immune interactions and warrant further investigation.