Inflammatory blood-based biomarkers to aid in the assessment and prognostication of traumatic brain injury: a TRACK-TBI study.
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Yue John K, Fu Allen Y, Jain Sonia, Puccio Ava M, Eagle Shawn R, Korley Frederick K, van Essen Thomas A, Samanta Romit, Li Lucia M, Roberts Christopher J, Caldwell David J, Elguindy Mahmoud M, Vassar Mary J, Belton Patrick J, Bhattacharyay Shubhayu, Nelson Lindsay D, Tracey Joye X, Etemad Leila L, Gotthardt Christine J, Satris Gabriela G, Wang Maxwell B, Demos Catherine, Sigal George B, Amorim Edilberto, Madhok Debbie Y, Radabaugh Hannah L, Ferguson Adam R, Markowitz Amy J, Robertson Claudia S, Valadka Alex B, Mukherjee Pratik, Yuh Esther L, McCrea Michael A, Hinson H E, Schneider Andrea L C, Sun Xiaoying, Okonkwo David O, Kobeissy Firas H, Manley Geoffrey T, Diaz-Arrastia Ramon, Wang Kevin K W, TRACK-TBI Investigators
Аннотация
METHODS: The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study prospectively enrolled TBI patients presenting to 18 United States trauma centers with head computed tomography (CT) on day 1 (D1; < 24-h post-injury). Data were extracted from TRACK-TBI subjects with D1 and 2-week (W2) plasma samples and 6-month functional outcomes, yielding 369 TBI subjects, 100 orthopedic trauma controls (OC), and 69 healthy controls. Twenty-seven inflammatory biomarkers were analyzed (MesoScale Diagnostics). TBI severity was defined using Glasgow Coma Scale (GCS; 3-12/13-15) and radiographic intracranial injury (CT-positive/CT-negative). Multivariable logistic regressions examined biomarkers as predictors of 6-month unfavorable outcomes (Glasgow Outcome Scale-Extended = 1-4 (death/severe-disability)), and adjusted for clinico-demographic factors and multiple comparisons. Adjusted odds ratios (AOR [95% confidence interval]) per log2-unit increase in biomarker level were reported.
RESULTS: Ten biomarkers (c-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-1ꞵ, IL-2, IL-4, IL-6, IL-10, IL-15, IL-17A, tumor necrosis factor (TNF)-α) differed significantly between GCS 3-12 vs. 13-15 TBI, CT-positive vs. CT-negative TBI, and GCS 3-12 TBI vs. OC, at both D1 and W2 (p < 0.001). IL-6, CRP, and SAA showed good discrimination of clinical TBI severity (D1/W2 area under-the-curve (AUC): 0.87/0.87, 0.82/0.88, 0.80/0.85, respectively), and moderate-to-good discrimination of radiographic TBI severity (D1/W2 AUC: 0.81/0.82, 0.78/0.83, 0.77/0.79, respectively). Five W2 biomarkers emerged as multivariable predictors of 6-month unfavorable outcomes (IL-15: AOR = 2.26 [1.14-4.49]; SAA: AOR = 1.91 [1.37-2.67]; IL-6: AOR = 1.80 [1.25-2.61]; IL-17A: AOR = 1.72 [1.24-2.39]; CRP: AOR = 1.40 [1.06-1.85]).
CONCLUSIONS: Ten circulating inflammatory proteins were associated with TBI diagnosis and severity at D1 and W2. Of these, five biomarkers expressed subacute (W2) levels predictive of 6-month death/severe-disability, underscoring their potential for validation as a novel biomarker class and integration into TBI prognostic models. Distillation of pro- and anti-inflammatory biomarker cascades in TBI could facilitate precision medicine approaches for risk stratification and therapeutic modulation.