BackgroundInterleukin-1 receptor-associated kinase 3 (IRAK3) may modulate inflammation in brain immunity. We determined the prognostic role of serum IRAK3 in severe traumatic brain injury (sTBI). MethodsIn this prospective longitudinal cohort study, serum IRAK3 concentrations of 131 sTBI patients and 131 controls were quantified. Extended Glasgow outcome scale (GOSE) scores of 1–4 at 180 days after trauma signified a poor prognosis. Univariate and multivariate analyses were sequentially adopted to appraise severity correlations and prognosis associations. ResultsThere were significantly higher serum IRAK3 concentrations in patients than in controls. Serum IRAK3 concentrations of patients were independently correlated with Glasgow coma scale (GCS) scores, Rotterdam computed tomography (CT) scores and posttraumatic180-day GOSE scores. Also, IRAK3 concentrations were independently associated with 180-day poor prognosis, but not with death. Prognosis prediction model, in which GCS scores, Rotterdam scores and serum IRAK3 concentrations were merged, was portrayed using the nomogram. The model was rather stable, clinically usable and efficiently discriminative of poor prognosis under calibration curve, decision curve and receiver operating characteristic curve. ConclusionsA substantial enhancement of serum IRAK3 concentrations after head trauma is independently related to severity and neurological outcome, substantializing serum IRAK3 as a promising prognostic biomarker of sTBI.