TY - JOUR
T1 - Untargeted blood serum proteomics identifies novel proteins related to neurological recovery after human spinal cord injury
AU - Garcia-Ovejero, Daniel
AU - Beyerer, Evelyn
AU - Mach, Orpheus
AU - Leister, Iris
AU - Strowitzki, Martin
AU - Wutte, Christof
AU - Maier, Doris
AU - Kramer, John Lk
AU - Aigner, Ludwig
AU - Arevalo-Martin, Angel
AU - Grassner, Lukas
N1 - Beyerer, Leister, Aigner, Grassner: Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria; Leister, Grassner, Aigner: Lehr-KH: Spinal Cord Injury Center, BG Trauma Center, Murnau, Germany; ParaMove, SCI Research Unit, BG Tauma Center Murnau, Germany and Paracelsus Medical University Salzburg, Salzburg, Austria; Grassner: Department of Neurosurgery, Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria, Wutte: Department of Neurosurgery, BG Trauma Center, Murnau, Germany.
PY - 2024/7/17
Y1 - 2024/7/17
N2 - BACKGROUND: The discovery of new prognostic biomarkers following spinal cord injury (SCI) is a rapidly growing field that could help uncover the underlying pathological mechanisms of SCI and aid in the development of new therapies. To date, this search has largely focused on the initial days after the lesion. However, during the subacute stage of SCI (weeks to months after the injury), there remains potential for sensorimotor recovery, and numerous secondary events develop in various organs. Additionally, the confounding effects of early interventions after the injury are less likely to interfere with the results.METHODS: In this study, we conducted an untargeted proteomics analysis to identify biomarkers of recovery in blood serum samples during the subacute phase of SCI patients, comparing those with strong recovery to those with no recovery between 30 and 120 days. We analyzed the fraction of serum that is depleted of the most abundant proteins to unmask proteins that would otherwise go undetected. Linear models were used to identify peptides and proteins related to neurological recovery and we validated changes in some of these proteins using Enzyme-linked Immunosorbent Assay (ELISA).RESULTS: Our findings reveal that differences in subacute recovery after SCI (from 30 to 120 days) are associated with an enrichment in proteins involved in inflammation, coagulation, and lipid metabolism. Technical validation using commercial ELISAs further confirms that high levels of SERPINE1 and ARHGAP35 are associated with strong neurological recovery, while high levels of CD300a and DEFA1 are associated with a lack of recovery.CONCLUSIONS: Our study identifies new candidates for biomarkers of neurological recovery and for novel therapeutic targets after SCI.
AB - BACKGROUND: The discovery of new prognostic biomarkers following spinal cord injury (SCI) is a rapidly growing field that could help uncover the underlying pathological mechanisms of SCI and aid in the development of new therapies. To date, this search has largely focused on the initial days after the lesion. However, during the subacute stage of SCI (weeks to months after the injury), there remains potential for sensorimotor recovery, and numerous secondary events develop in various organs. Additionally, the confounding effects of early interventions after the injury are less likely to interfere with the results.METHODS: In this study, we conducted an untargeted proteomics analysis to identify biomarkers of recovery in blood serum samples during the subacute phase of SCI patients, comparing those with strong recovery to those with no recovery between 30 and 120 days. We analyzed the fraction of serum that is depleted of the most abundant proteins to unmask proteins that would otherwise go undetected. Linear models were used to identify peptides and proteins related to neurological recovery and we validated changes in some of these proteins using Enzyme-linked Immunosorbent Assay (ELISA).RESULTS: Our findings reveal that differences in subacute recovery after SCI (from 30 to 120 days) are associated with an enrichment in proteins involved in inflammation, coagulation, and lipid metabolism. Technical validation using commercial ELISAs further confirms that high levels of SERPINE1 and ARHGAP35 are associated with strong neurological recovery, while high levels of CD300a and DEFA1 are associated with a lack of recovery.CONCLUSIONS: Our study identifies new candidates for biomarkers of neurological recovery and for novel therapeutic targets after SCI.
KW - Humans
KW - Spinal Cord Injuries/blood
KW - Proteomics
KW - Recovery of Function
KW - Male
KW - Female
KW - Adult
KW - Middle Aged
KW - Biomarkers/blood
KW - Blood Proteins/metabolism
U2 - 10.1186/s12967-024-05344-y
DO - 10.1186/s12967-024-05344-y
M3 - Original Article
C2 - 39020346
SN - 1479-5876
VL - 22
SP - 666
JO - Journal of translational medicine
JF - Journal of translational medicine
IS - 1
M1 - 666
ER -