Natural Killer (NK) Cell Functionality after human Spinal Cord Injury (SCI): protocol of a prospective, longitudinal study.
BACKGROUND
Natural killer (NK) cells comprise the main components of lymphocyte-mediated nonspecific immunity. Through their effector function they play a crucial role combating bacterial and viral challenges. They are also thought to be key contributors to the systemic spinal cord injury-induced immune-deficiency syndrome (SCI-IDS). SCI-IDS increases susceptibility to infection and extends to the post-acute and chronic phases after SCI.


METHODS
The prospective study of NK cell function after traumatic SCI was carried out in two centers in Berlin, Germany. SCI patients and control patients with neurologically silent vertebral fracture also undergoing surgical stabilization were enrolled. Furthermore healthy controls were included to provide reference data. The NK cell function was assessed at 7 (5-9) days, 14 days (11-28) days, and 10 (8-12) weeks post-trauma. Clinical documentation included the American Spinal Injury Association (ASIA) impairment scale (AIS), neurological level of injury, infection status, concomitant injury, and medications. The primary endpoint of the study is CD107a expression by NK cells (cytotoxicity marker) 8-12 weeks following SCI. Secondary endpoints are the NK cell's TNF-α and IFN-γ production by the NK cells 8-12 weeks following SCI.


CONCLUSIONS
The protocol of this study was developed to investigate the hypotheses whether i) SCI impairs NK cell function throughout the post-acute and sub-acute phases after SCI and ii) the degree of impairment relates to lesion height and severity. A deeper understanding of the SCI-IDS is crucial to enable strategies for prevention of infections, which are associated with poor neurological outcome and elevated mortality.


BACKGROUND
DRKS00009855 .
Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Inês
I
Laginha
Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Marcel A
MA
Kopp
Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Department of Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Claudia
C
Druschel
Department of Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Klaus-Dieter
KD
Schaser
Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|F.M.Kirby Neurobiology Center, Childrens's Hospital and Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA.
Benedikt
B
Brommer
Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Rick C
RC
Hellmann
Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Ralf
R
Watzlawick
Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Ramin-Raul
RR
Ossami-Saidi
Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Harald
H
Prüss
Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Vieri
V
Failli
Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.
Christian
C
Meisel
Treatment Centre for Spinal Cord Injuries, Trauma Hospital Berlin, Warener Straße 7, 12683, Berlin, Germany.
Thomas
T
Liebscher
Treatment Centre for Spinal Cord Injuries, Trauma Hospital Berlin, Warener Straße 7, 12683, Berlin, Germany.
Erik
E
Prilipp
Treatment Centre for Spinal Cord Injuries, Trauma Hospital Berlin, Warener Straße 7, 12683, Berlin, Germany.
Andreas
A
Niedeggen
Treatment Centre for Spinal Cord Injuries, Trauma Hospital Berlin, Warener Straße 7, 12683, Berlin, Germany.
Axel
A
Ekkernkamp
Department for Biostatistics and Clinical Epidemiology, Charitéplatz 1, 10117, Berlin, Germany.|Department of Neurology, Spinal Cord Injury Division, The Neuroscience Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, 43210, USA.
Ulrike
U
Grittner
Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Sophie K
SK
Piper
Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.|Center for Stroke Research Berlin, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.
Ulrich
U
Dirnagl
Deutsches Rheuma-Forschungszentrum (DRFZ), Charitéplatz 1, 10117, Berlin, Germany.
Monica
M
Killig
Deutsches Rheuma-Forschungszentrum (DRFZ), Charitéplatz 1, 10117, Berlin, Germany.
Chiara
C
Romagnani
Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. Jan.Schwab@osumc.edu.|Clinical and Experimental Spinal Cord Injury Research (Neuroparaplegiology), Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. Jan.Schwab@osumc.edu.|Treatment Centre for Spinal Cord Injuries, Trauma Hospital Berlin, Warener Straße 7, 12683, Berlin, Germany. Jan.Schwab@osumc.edu.|Department of Neurology, Spinal Cord Injury Division, The Neuroscience Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, 43210, USA. Jan.Schwab@osumc.edu.|Department of Neuroscience and Center for Brain and Spinal Cord Repair, Department of Physical Medicine and Rehabilitation, The Neurological Institute, The Ohio State University, Wexner Medical Center, Columbus, OH, 43210, USA. Jan.Schwab@osumc.edu.|Head Spinal Cord Injury Division, Department Neurology, The William E. Hunt and Charlotte M. Curtis Chair in Neuroscience, The Neurological Institute, The Ohio State University - Wexner Medical Center, 395 W. 12th Ave, 7th Floor, Columbus, OH, 43210, USA. Jan.Schwab@osumc.edu.
Jan M
JM
Schwab
D000328:Adult; D015415:Biomarkers; D016022:Case-Control Studies; D002478:Cells, Cultured; D002985:Clinical Protocols; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008137:Longitudinal Studies; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis; D008297:Male; D011446:Prospective Studies; D013119:Spinal Cord Injuries / Q000150:complications / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D055815:Young Adult
D015415:Biomarkers; D052118:Lysosomal-Associated Membrane Protein 1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
Immune paralysis; Lesion height dependency; NK cells function; Spinal cord injury