Year: 2023
Type: article
Study design: Observational Study
Abstract: Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI.
Source: Brain
Authors: Marcel A Kopp, Christian Meisel, Thomas Liebscher, Ralf Watzlawick, Paolo Cinelli, Oliver Schweizerhof, Christian Blex, Tom Lübstorf, Erik Prilipp, Andreas Niedeggen, Claudia Druschel, Klaus-Dieter Schaser, Guido A Wanner, Armin Curt, Gertraut Lindemann, Natalia Nugeva, Michael G Fehlings, Peter Vajkoczy, Mario Cabraja, Julius Dengler, Wolfgang Ertel, Axel Ekkernkamp, Kerstin Rehahn, Peter Martus, Hans-Dieter Volk, Nadine Unterwalder, Uwe Kölsch, Benedikt Brommer, Rick C Hellmann, Elias Baumgartner, Julian Hirt, Laura-Christin Geurtz, Ramin Raul Ossami Saidy, Harald Prüss, Ines Laginha, Vieri Failli, Ulrike Grittner, Ulrich Dirnagl, Jan M Schwab
Institutions: Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Charité – Universitätsmedizin Berlin, Berlin-Brandenburger Centrum für Regenerative Therapien, Unfallkrankenhaus Berlin, University Medical Center Freiburg, University of Zurich, University Hospital Zurich, University Hospital Carl Gustav Carus, Universitätsklinik Balgrist, University Health Network, Toronto Western Hospital, University of Toronto, Vivantes Klinikum, Helios Hospital Bad Saarow, University of Tübingen, Boston Children's Hospital, Harvard University, DRK Kliniken Berlin, German Center for Neurodegenerative Diseases, Center for Stroke Research Berlin, The Ohio State University Wexner Medical Center, The Ohio State University
Language: English
Topic: Spinal Cord Injury Research
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,550
Funders: Craig H. Neilsen Foundation, Ohio State University, Wings for Life, European Commission, Deutsche Forschungsgemeinschaft, Berlin-Brandenburger Centrum für Regenerative Therapien, National Institutes of Health, National Institute of Neurological Disorders and Stroke, National Institute on Disability, Independent Living, and Rehabilitation Research
Awards: G192810579, G221990578, Reducing Infection Susceptibility by Immune Function Restoration in Spinal Cord Injury, G471156142, G4781570407, G5125543898, TRR 167: Entwicklung, Funktion und Potential von myeloiden Zellen im zentralen Nervensystem (NeuroMac), G6857544921, G7412116791, Protecting Endogenous Recovery from the "Infectious Insult" in Spinal Cord Injury
OpenAlex ID: W4382345075