Diagnostic blood RNA profiles for human acute spinal cord injury

Nikos Kyritsis; Abel Torres-Espín; Patrick G Schupp; J Russell Huie; Austin Chou; Xuan Duong-Fernandez; Leigh H Thomas; Rachel E Tsolinas; Debra D Hemmerle; Lisa U Pascual; Vineeta Singh; Jonathan Z Pan; Jason F Talbott; William D Whetstone; John F Burke; Anthony M DiGiorgio; Philip R Weinstein; Geoffrey T Manley; Sanjay S Dhall; Adam R Ferguson; Michael C Oldham; Jacqueline C Bresnahan; Michael S Beattie

doi:10.1084/jem.20201795

Diagnostic blood RNA profiles for human acute spinal cord injury

J Exp Med. 2021 Mar 1;218(3):e20201795. doi: 10.1084/jem.20201795.

Authors

Nikos Kyritsis^{1

2

3}, Abel Torres-Espín^{1

2

3}, Patrick G Schupp^{2

4}, J Russell Huie^{1

2

3}, Austin Chou^{1

2

3}, Xuan Duong-Fernandez^{1

2

3}, Leigh H Thomas^{1

2

3}, Rachel E Tsolinas^{1

2

3}, Debra D Hemmerle^{1

2

3}, Lisa U Pascual⁵, Vineeta Singh^{1

6}, Jonathan Z Pan^{1

7}, Jason F Talbott^{3

8}, William D Whetstone⁹, John F Burke², Anthony M DiGiorgio^{1

2

3}, Philip R Weinstein^{2

6

10}, Geoffrey T Manley^{1

2

3}, Sanjay S Dhall^{1

2

3}, Adam R Ferguson^{1

2

3

11}, Michael C Oldham^{2

4}, Jacqueline C Bresnahan^{1

2

3}, Michael S Beattie^{1

2

3

11}

Affiliations

¹ Weill Institute for Neurosciences, Brain and Spinal Injury Center, University of California, San Francisco, San Francisco, CA.
² Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA.
³ Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, CA.
⁴ Brain Tumor Center, University of California, San Francisco, San Francisco, CA.
⁵ Orthopaedic Trauma Institute, Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA.
⁶ Department of Neurology, University of California, San Francisco, San Francisco, CA.
⁷ Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, CA.
⁸ Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA.
⁹ Department of Emergency Medicine, University of California, San Francisco, San Francisco, CA.
¹⁰ Weill Institute for Neurosciences, Institute for Neurodegenerative Diseases, Spine Center, University of California, San Francisco, San Francisco, CA.
¹¹ San Francisco Veterans Affairs Healthcare System, San Francisco, CA.

Abstract

Diagnosis of spinal cord injury (SCI) severity at the ultra-acute stage is of great importance for emergency clinical care of patients as well as for potential enrollment into clinical trials. The lack of a diagnostic biomarker for SCI has played a major role in the poor results of clinical trials. We analyzed global gene expression in peripheral white blood cells during the acute injury phase and identified 197 genes whose expression changed after SCI compared with healthy and trauma controls and in direct relation to SCI severity. Unsupervised coexpression network analysis identified several gene modules that predicted injury severity (AIS grades) with an overall accuracy of 72.7% and included signatures of immune cell subtypes. Specifically, for complete SCIs (AIS A), ROC analysis showed impressive specificity and sensitivity (AUC: 0.865). Similar precision was also shown for AIS D SCIs (AUC: 0.938). Our findings indicate that global transcriptomic changes in peripheral blood cells have diagnostic and potentially prognostic value for SCI severity.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Case-Control Studies
Gene Expression Profiling
Gene Expression Regulation
Gene Ontology
Gene Regulatory Networks
Humans
Leukocytes / metabolism
Logistic Models
RNA / blood*
RNA / genetics
Spinal Cord Injuries / blood*
Spinal Cord Injuries / diagnosis*
Spinal Cord Injuries / genetics
Spinal Cord Injuries / pathology
Transcriptome / genetics

Substances

RNA

Abstract

Publication types

MeSH terms

Substances

Grants and funding