High-Sensitivity C-Reactive Protein is a Prognostic Biomarker of Six-Month Disability after Traumatic Brain Injury: Results from the TRACK-TBI Study
Linda Xu, John K. Yue, Frederick K. Korley, Ava M. Puccio, Esther L. Yuh, Xiaoying Sun, Miri Rabinowitz, Mary J. Vassar, Sabrina R. Taylor, Ethan A. Winkler, Ross C. Puffer, Hansen Deng, Michael McCrea, Murray B. Stein, Claudia S. Robertson, Harvey S. Levin, Sureyya Dikmen, Nancy Temkin, Joseph T. Giacino, Pratik Mukherjee, Kevin Wang, David O. Okonkwo, Amy J. Markowitz, Sonia Jain, Geoffrey T. Manley, Ramon Diaz‐Arrastia, The TRACK-TBI Investigators, Opeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, M. Ross Bullock, Randall M. Chesnut, John D. Corrigan, Karen Crawford, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel C. Gardner, Etienne Gaudette, Dana P. Goldman, Luis González, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, Joel H. Kramer, Natalie Kreitzer, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair J. Martin, Thomas W. McAllister, Randall Merchant, Lindsay D. Nelson, Laura B. Ngwenya, Florence Noël, David O. Okonkwo, Eva Palacios, Daniel Perl, Jonathan Rosand, Angelle M. Sander, Gabriella Satris, David M. Schnyer, Seth Seabury, Arthur W. Toga, Alex VaOpeolu Adeoye, Neeraj Badjatia, Kim Boase, Yelena Bodien, M. Ross Bullock, Randall M. Chesnut, John D. Corrigan, Karen Crawford, Ann-Christine Duhaime, Richard Ellenbogen, V. Ramana Feeser, Adam R. Ferguson, Brandon Foreman, Raquel C. Gardner, Etienne Gaudette, Dana P. Goldman, Luis González, Shankar Gopinath, Rao Gullapalli, J. Claude Hemphill, Gillian Hotz, Joel H. Kramer, Natalie Kreitzer, Chris Lindsell, Joan Machamer, Christopher Madden, Alastair J. Martin, Thomas W. McAllister, Randall Merchant, Lindsay D. Nelson, Laura B. Ngwenya, Florence Noël
Abstract
Systemic inflammation impacts outcome after traumatic brain injury (TBI), but most TBI biomarker studies have focused on brain-specific proteins. C-reactive protein (CRP) is a widely used biomarker of inflammation with potential as a prognostic biomarker after TBI. The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study prospectively enrolled TBI patients within 24 h of injury, as well as orthopedic injury and uninjured controls; biospecimens were collected at enrollment. A subset of hospitalized participants had blood collected on day 3, day 5, and 2 weeks. High-sensitivity CRP (hsCRP) and glial fibrillary acidic protein (GFAP) were measured. Receiver operating characteristic analysis was used to evaluate the prognostic ability of hsCRP for 6-month outcome, using the Glasgow Outcome Scale-Extended (GOSE). We included 1206 TBI subjects, 122 orthopedic trauma controls (OTCs), and 209 healthy controls (HCs). Longitudinal biomarker sampling was performed in 254 hospitalized TBI subjects and 19 OTCs. hsCRP rose between days 1 and 5 for TBI and OTC subjects, and fell by 2 weeks, but remained elevated compared with HCs (p < 0.001). Longitudinally, hsCRP was significantly higher in the first 2 weeks for subjects with death/severe disability (GOSE <5) compared with those with moderate disability/good recovery (GOSE ≥5); AUC was highest at 2 weeks (AUC = 0.892). Combining hsCRP and GFAP at 2 weeks produced AUC = 0.939 for prediction of disability. Serum hsCRP measured within 2 weeks of TBI is a prognostic biomarker for disability 6 months later. hsCRP may have utility as a biomarker of target engagement for anti-inflammatory therapies.