نبذة مختصرة : Background Acute pancreatitis (AP) varies in severity, and traditional severity stratifications often fail to predict its early course. In people living with HIV (PLWH), chronic immune dysregulation leads to aberrant cytokine responses which influence biomarker performance. We hypothesize that in regions with high prevalence of HIV infection, HIV status will influence the immune biomarker performance in the prediction of severity of AP. Methodology In this prospective case-control study conducted in KwaZulu-Natal, 144 adult patients with AP (29 % PLWH) were enrolled. Blood samples were collected within 24 h of admission, and plasma was isolated and cryopreserved before cytokine levels were quantified using a multiplex electrochemiluminescence assay. Clinical severity was assessed using revised Atlanta classification. Receiver operating characteristic analyses were performed to derive optimal biomarker thresholds based on Youden's index, with significance set at p < 0.01. Results In people without HIV, IL-6, TNF-α, IL-15, IL-17, and MCP-1 were significantly upregulated in severe AP, with IL-15 demonstrating the highest discriminative performance (AUC 0.917; optimal cut-off 3.79 pg/mL; sensitivity 94.1 %, specificity 72.9 %). In PLWH patients, TNF-α was the only cytokine significantly associated with AP severity (AUC 0.974; optimal cut-off 9.42 pg/mL; sensitivity 100 %, specificity 97.4 %), while IL-17 did not predict severity in PLWH. Across the combined cohort, cytokine thresholds were higher in PLWH. Conclusion Distinct immune signatures correlate with AP severity and are significantly influenced by HIV status. IL-15 outperformed IL-6, TNF-α, IL-17, and MCP-1 in people without HIV, whereas TNF-α was the only predictor of severity in PLWH. Higher thresholds for prediction of severity in PLWH underscore the need for HIV-specific biomarker thresholds and further research into tailored severity stratification, and development of immunomodulating therapies in AP.
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