{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T12:22:34Z","timestamp":1782130954007,"version":"3.54.5"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with Type 1 Diabetes Mellitus (T1DM) are at increased risk for severe COVID-19 due to chronic inflammation, immune dysregulation, and impaired antiviral responses. However, the combined contribution of cytokine imbalance, host genetic variation, and systemic inflammation on COVID-19 severity in this population remains incompletely understood. This study aimed to investigate inflammatory biomarkers, interleukin profiles and immunogenetic factor associated with COVID -19 outcomes in T1DM patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 220 individuals were enrolled, including 160 T1DM patients with confirmed COVID-19 and 60 healthy controls. Serum concentrations of IL-6, IL-10, IL-12A, and IL-18 were quantified using ELISA, along with clinical inflammatory markers (CRP, D-dimer, and NLR). Genetic polymorphisms in the IL-10, IL-12A, IL-6, and IL-18 genes were analyzed using PCR-ARMS. Statistical analyses included group comparisons and correlation analysis. In addition, supervised machine-learning (ML) approaches (Decision Tree and Random Forest) were applied within the T1DM COVID-19 cohort to identify biomarkers predictive of disease severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients exhibited significantly elevated cytokine levels and inflammatory markers compared to controls (all p &amp;lt; 0.001). The IL-10 polymorphism (rs1800872) was significantly associated with increased disease susceptibility, with the G allele conferring a higher risk (p&amp;lt;0.0001, OR = 2.85 CI95% [1.83-4.43]). IL-12 correlated positively with IL-18 (r = 0.41, p &amp;lt; 0.001) and negatively with IL-6 (r = \u22120.22, p = 0.005). ML analyses identified IL-18, CRP, and IL-6 as the most informative biomarkers of COVID-19 severity, with IL-18 showing the highest feature importance (0.276, 0.202, and 0.175, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study highlights the critical role of inflammatory biomarkers and host genetic factors in COVID-19 severity among T1DM patients and identifies IL-18 as a robust and clinically relevant biomarker for risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1736234","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T06:32:35Z","timestamp":1772433155000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cytokine profiles, genetic polymorphisms, and systemic inflammatory markers in type 1 diabetes 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