Response Of Blood Cells Research Articles

Sphingosine Increases ATP Release From Red Blood Cells

Background: RBC plays a pivotal role in oxygen delivery, improving distribution where it needs. When RBC enters a low oxygen area, a mechanism mediated by a signaling pathway releases ATP, responsible for vasodilatation. Objective: Clarify the potential role of sphingosine on the release of ATP from RBC. Methods: ATP release increases after sphingosine exposure in RBC under low oxygen conditions. ATP release in deoxygenated RBC shows data like that of control RBC: (1) RBC after band 3 modification by 4,4'- diisothio-cyanato-stilbene- 2,2'-disulphonic acid (DIDS); (2) CO-treated RBC. Unlike phosphofructokinase, adenylate cyclase (AC) activity increases after exposure to sphingosine. Results: We show that cAMP synthesis and ATP release are not failed in sphingosine-treated red blood cells in response to incubation with mastoparan 7, forskolin plus 3-isobutyl-1-methyl xanthine, agents that stimulate cAMP synthesis. Conclusion: Deoxy-hemoglobin, band 3, and AC are involved in the signaling pathway responsible for ATP released after sphingosine exposure.

Sphingosine Increases ATP Release From Red Blood Cells

Background: RBC plays a pivotal role in oxygen delivery, improving distribution where it needs. When RBC enters a low oxygen area, a mechanism mediated by a signaling pathway releases ATP, responsible for vasodilatation. Objective: Clarify the potential role of sphingosine on the release of ATP from RBC. Methods: ATP release increases after sphingosine exposure in RBC under low oxygen conditions. ATP release in deoxygenated RBC shows data like that of control RBC: (1) RBC after band 3 modification by 4,4'- diisothio-cyanato-stilbene- 2,2'-disulphonic acid (DIDS); (2) CO-treated RBC. Unlike phosphofructokinase, adenylate cyclase (AC) activity increases after exposure to sphingosine. Results: We show that cAMP synthesis and ATP release are not failed in sphingosine-treated red blood cells in response to incubation with mastoparan 7, forskolin plus 3-isobutyl-1-methyl xanthine, agents that stimulate cAMP synthesis. Conclusion: Deoxy-hemoglobin, band 3, and AC are involved in the signaling pathway responsible for ATP released after sphingosine exposure.

Toll-Like Receptor 7 Agonist RG7854 Mediates Therapeutic Efficacy and Seroconversion in Woodchucks With Chronic Hepatitis B.

Conventional treatment of chronic hepatitis B (CHB) is rarely curative due to the immunotolerant status of patients. RG7854 is an oral double prodrug of a toll-like receptor 7 (TLR7) agonist that is developed for the treatment of CHB. The therapeutic efficacy, host immune response, and safety of RG7854 were evaluated in the woodchuck model of CHB. Monotreatment with the two highest RG7854 doses and combination treatment with the highest RG7854 dose and entecavir (ETV) suppressed viral replication, led to loss of viral antigens, and induced seroconversion in responder woodchucks. Since viral suppression and high-titer antibodies persisted after treatment ended, this suggested that a sustained antiviral response (SVR) was induced by RG7854 in a subset of animals. The SVR rate, however, was comparable between both treatment regimens, suggesting that the addition of ETV did not enhance the therapeutic efficacy of RG7854 although it augmented the proliferation of blood cells in response to viral antigens and magnitude of antibody titers. The induction of interferon-stimulated genes in blood by RG7854/ETV combination treatment demonstrated on-target activation of TLR7. Together with the virus-specific blood cell proliferation and the transient elevations in liver enzymes and inflammation, this suggested that cytokine-mediated non-cytolytic and T-cell mediated cytolytic mechanisms contributed to the SVR, in addition to the virus-neutralizing effects by antibody-producing plasma cells. Both RG7854 regimens were not associated with treatment-limiting adverse effects but accompanied by dose-dependent, transient neutropenia and thrombocytopenia. The study concluded that finite, oral RG7854 treatment can induce a SVR in woodchucks that is based on the retrieval of antiviral innate and adaptive immune responses. This supports future investigation of the TLR7 agonist as an immunotherapeutic approach for achieving functional cure in patients with CHB.

Durable and dynamic hTERT immune responses following vaccination with the long-peptide cancer vaccine UV1: long-term follow-up of three phase I clinical trials

BackgroundTherapeutic cancer vaccines represent a promising approach to improve clinical outcomes with immune checkpoint inhibition. UV1 is a second generation telomerase-targeting therapeutic cancer vaccine being investigated across multiple indications. Although...

The White Blood Cell Response in Sputum in Viral and Bacterial Pneumonias.

The White Blood Cell Response in Sputum in Viral and Bacterial Pneumonias.

Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma

CD8+ T cell reactivity towards tumor mutation-derived neoantigens is widely believed to facilitate the antitumor immunity induced by immune checkpoint blockade (ICB). Here we show that broadening in the number of neoantigen-reactive CD8+ T cell (NART) populations between pre-treatment to 3-weeks post-treatment distinguishes patients with controlled disease compared to patients with progressive disease in metastatic urothelial carcinoma (mUC) treated with PD-L1-blockade. The longitudinal analysis of peripheral CD8+ T cell recognition of patient-specific neopeptide libraries consisting of DNA barcode-labelled pMHC multimers in a cohort of 24 patients from the clinical trial NCT02108652 also shows that peripheral NARTs derived from patients with disease control are characterised by a PD1+ Ki67+ effector phenotype and increased CD39 levels compared to bystander bulk- and virus-antigen reactive CD8+ T cells. The study provides insights into NART characteristics following ICB and suggests that early-stage NART expansion and activation are associated with response to ICB in patients with mUC.

Microrheological responses of red blood cells to gaseous mediators under physiological and pathophysiological conditions

Microrheological responses of red blood cells to gaseous mediators under physiological and pathophysiological conditions

T-cell exhaustion and residency dynamics inform clinical outcomes in hepatocellular carcinoma

Despite recent translation of immunotherapies into clinical practice, the immunobiology of hepatocellular carcinoma (HCC), in particular the role and clinical relevance of exhausted and liver-resident T cells remain unclear. We therefore dissected the landscape of exhausted and resident T cell responses in the peripheral blood and tumor microenvironment of patients with HCC. Lymphocytes were isolated from the blood, tumor and tumor-surrounding liver tissue of patients with HCC (n= 40, n= 10 treated with anti-PD-1 therapy). Phenotype, function and response to anti-PD-1 were analyzed by mass and flow cytometry exvivo and invitro, tissue residence was further assessed by immunohistochemistry and imaging mass cytometry. Gene signatures were analyzed in silico. We identified significant enrichment of heterogeneous populations of exhausted CD8+ T cells (TEX) in the tumor microenvironment. Strong enrichment of severely exhausted CD8 T cells expressing multiple immune checkpoints in addition to PD-1 was linked to poor progression-free and overallsurvival. In contrast, PD-1 was also expressed on a subset of more functional and metabolically active CD103+ tissue-resident memory T cells (TRM) that expressed few additional immune checkpoints and were associated with better survival. TEX enrichment was independent of BCLC stage, alpha-fetoprotein levels or age as a variable for progression-free survival in our cohort. These findings were in line with in silico gene signature analysis of HCC tumor transcriptomes from The Cancer Genome Atlas. A higher baseline TRM/TEX ratio was associated with disease control in anti-PD-1-treated patients. Our data provide information on the role of peripheral and intratumoral TEX-TRM dynamics in determining outcomes in patients with HCC. The dynamics between exhausted and liver-resident T cells have implications for immune-based diagnostics, rational patient selection and monitoring during HCC immunotherapies. The role of the immune response in hepatocellular carcinoma (HCC) remains unclear. T cells can mediate protection against tumor cells but are frequently dysfunctional andexhausted in cancer. We found that patients with a predominance of exhausted CD8+ T cells (TEX) had poor survivalcompared to patients with a predominance of tissue-resident memory T cells (TRM). This correlated with the molecular profile, metabolic and functional status of these cell populations. The enrichment of TEX was independently associated with prognosis in addition to disease stage, age and tumor markers. A high TRM proportion was also associated with better outcomes following checkpoint therapy. Thus, these T-cell populations are novel biomarkers with relevance in HCC.

Characterization of immune responses in fully vaccinated individuals after breakthrough infection with the SARS-CoV-2 delta variant.

Breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been reported frequently in vaccinated individuals with waning immunity. In particular, a cluster of over 1,000 infections with the SARS-CoV-2 delta variant was identified in a predominantly fully vaccinated population in Provincetown, Massachusetts in July 2021. In this study, vaccinated individuals who tested positive for SARS-CoV-2 (n=16) demonstrated substantially higher serum antibody responses than vaccinated individuals who tested negative for SARS-CoV-2 (n=23), including 32-fold higher binding antibody titers and 31-fold higher neutralizing antibody titers against the SARS-CoV-2 delta variant. Vaccinated individuals who tested positive also showed higher mucosal antibody responses in nasal secretions and higher Spike protein-specific CD8+ T cell responses in peripheral blood than did vaccinated individuals who tested negative. These data demonstrate that fully vaccinated individuals developed robust anamnestic antibody and T cell responses following infection with the SARS-CoV-2 delta variant. Moreover, these findings suggest that population immunity will likely increase over time by a combination of widespread vaccination and breakthrough infections.

Bet v 1 triggers antiviral-type immune signalling in birch-pollen-allergic individuals.

BackgroundIn allergic patients, clinical symptoms caused by pollen remind of symptoms triggered by viral respiratory infections, which are also the main cause of asthmatic exacerbations. In patients sensitized to birch pollen, Bet v 1 is the major symptom‐causing allergen. Immune mechanisms driving Bet v 1‐related responses of human blood cells have not been fully characterized.ObjectiveTo characterize the immune response to Bet v 1 in peripheral blood in patients allergic to birch pollen.MethodsThe peripheral blood mononuclear cells of birch‐allergic (n = 24) and non‐allergic (n = 47) adolescents were stimulated ex‐vivo followed by transcriptomic profiling. Systems‐biology approaches were employed to decipher disease‐relevant gene networks and deconvolution of associated cell populations.ResultsSolely in birch‐allergic patients, co‐expression analysis revealed activation of networks of innate immunity and antiviral signalling as the immediate response to Bet v 1 stimulation. Toll‐like receptors and signal transducer transcription were the main drivers of gene expression patterns. Macrophages and dendritic cells were the main cell subsets responding to Bet v 1.Conclusions and clinical relevanceIn birch‐pollen‐allergic patients, the activated innate immune networks seem to be, in part, the same as those activated during viral infections. This tendency of the immune system to read pollens as viruses may provide new insight to allergy prevention and treatment.

Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas.

BACKGROUNDLong-term prognosis of WHO grade II low-grade gliomas (LGGs) is poor, with a high risk of recurrence and malignant transformation into high-grade gliomas. Given the relatively intact immune system of patients with LGGs and the slow tumor growth rate, vaccines are an attractive treatment strategy.METHODSWe conducted a pilot study to evaluate the safety and immunological effects of vaccination with GBM6-AD, lysate of an allogeneic glioblastoma stem cell line, with poly-ICLC in patients with LGGs. Patients were randomized to receive the vaccines before surgery (arm 1) or not (arm 2) and all patients received adjuvant vaccines. Coprimary outcomes were to evaluate safety and immune response in the tumor.RESULTSA total of 17 eligible patients were enrolled — 9 in arm 1 and 8 in arm 2. This regimen was well tolerated with no regimen-limiting toxicity. Neoadjuvant vaccination induced upregulation of type-1 cytokines and chemokines and increased activated CD8+ T cells in peripheral blood. Single-cell RNA/T cell receptor sequencing detected CD8+ T cell clones that expanded with effector phenotype and migrated into the tumor microenvironment (TME) in response to neoadjuvant vaccination. Mass cytometric analyses detected increased tissue resident–like CD8+ T cells with effector memory phenotype in the TME after the neoadjuvant vaccination.CONCLUSIONThe regimen induced effector CD8+ T cell response in peripheral blood and enabled vaccine-reactive CD8+ T cells to migrate into the TME. Further refinements of the regimen may have to be integrated into future strategies.TRIAL REGISTRATIONClinicalTrials.gov NCT02549833.FUNDINGNIH (1R35NS105068, 1R21CA233856), Dabbiere Foundation, Parker Institute for Cancer Immunotherapy, and Daiichi Sankyo Foundation of Life Science.

The Significance of Toll-Like Receptors in the Neuroimmunologic Background of Alcohol Dependence.

Toll-like receptors (TLR) are a group of protein belonging to the family of Pattern Recognition Receptors (PRR) which have the ability to distinguish between an organism's own antigens and foreign ones and to induce immunological response. TLR play a significant part in non-specific immunity but at the same time they are also a vital element linking non-specific response to the specific one. A growing number of data seems to indicate that the non-specific immunity mechanisms affect the development and sustenance of alcohol addiction. Alcohol damages the organism's cells not only directly but also through an increase inintestinal permeability which induces innate immune response of peripheral blood cells. The signaling pathway of Toll-like receptors located on the surface of brain immune cells intensifies the inflammatory reaction and, through modifying gene expression of proinflammatory factors, unnaturally supports it. This overly protracted “sterile inflammatory reaction” positively correlates with alcohol craving affecting also the functioning of the reward system structures and increasing the risk of relapse of alcoholism. Recurrent alcoholic binges sensitize the microglia and cause an escalation in inflammatory reaction which also leads to neurodegeneration. The induction of innate immunity signaling pathways exposes clinical symptoms of alcohol addiction such as increased impulsivity, loss of behavioral control, depressive-anxiety symptoms and cognitive dysfunctions. Traditional methods of treating alcohol addiction have tended to focus predominantly on reducing symptoms which—given the frequency of relapses—seems insufficient. The aim of the present paper is to discuss the role of toll-like receptors as elements of the immunity system which, together with the nervous system, plays a crucial part in the pathogenesis of alcohol addiction. We also wish to present pharmacotherapeutic perspectives targeted at the neuroimmunological mechanisms of alcohol addiction.

The Route of Vaccine Administration Determines Whether Blood Neutrophils Undergo Long-Term Phenotypic Modifications.

Innate immunity modulates adaptive immunity and defines the magnitude, quality, and longevity of antigen-specific T- and B- cell immune memory. Various vaccine and administration factors influence the immune response to vaccination, including the route of vaccine delivery. We studied the dynamics of innate cell responses in blood using a preclinical model of non-human primates immunized with a live attenuated vaccinia virus, a recombinant Modified vaccinia virus Ankara (MVA) expressing a gag-pol-nef fusion of HIV-1, and mass cytometry. We previously showed that it induces a strong, early, and transient innate response, but also late phenotypic modifications of blood myeloid cells after two months when injected subcutaneously. Here, we show that the early innate effector cell responses and plasma inflammatory cytokine profiles differ between subcutaneous and intradermal vaccine injection. Additionally, we show that the intradermal administration fails to induce more highly activated/mature neutrophils long after immunization, in contrast to subcutaneous administration. Different batches of antibodies, staining protocols and generations of mass cytometers were used to generate the two datasets. Mass cytometry data were analyzed in parallel using the same analytical pipeline based on three successive clustering steps, including SPADE, and categorical heatmaps were compared using the Manhattan distance to measure the similarity between cell cluster phenotypes. Overall, we show that the vaccine per se is not sufficient for the late phenotypic modifications of innate myeloid cells, which are evocative of innate immune training. Its route of administration is also crucial, likely by influencing the early innate response, and systemic inflammation, and vaccine biodistribution.

Induction of T Cell Responses by Vaccination of a Streptococcus pneumoniae Whole-Cell Vaccine.

The induction of T cell responses by vaccination is important for protection against infection. We have previously shown that immunization with a killed Streptococcus pneumoniae whole-cell vaccine (SPWCV) by either intranasal immunization or subcutaneous immunization induced T cell responses to SPWCV. Protection against colonization by S. pneumoniae is dependent on CD4+ IL-17A production induced by immunization. Here, we present detailed protocols for preparation of SPWCV, immunization of mice, and assay for T cell responses in blood and splenocytes in immunized mice.

Heterogeneity of Hematological Response to Hypoxia and Short-Term or Medium-Term Bed Rest.

Hematological changes are commonly observed following prolonged exposure to hypoxia and bed rest. Typically, such responses have been reported as means and standard deviations, however, investigation into the responses of individuals is insufficient. Therefore, the present study retrospectively assessed individual variation in the hematological responses to severe inactivity (bed rest) and hypoxia. The data were derived from three-bed rest projects: two 10-d (LunHab project: 8 males; FemHab project: 12 females), and one 21-d (PlanHab project: 11 males). Each project comprised a normoxic bed rest (NBR; PIO2=133mmHg) and hypoxic bed rest (HBR; PIO2=91mmHg) intervention, where the subjects were confined in the Planica facility (Rateče, Slovenia). During the HBR intervention, subjects were exposed to normobaric hypoxia equivalent to an altitude of 4,000m. NBR and HBR interventions were conducted in a random order and separated by a washout period. Blood was drawn prior to (Pre), during, and post bed rest (R1, R2, R4) to analyze the individual variation in the responses of red blood cells (RBC), erythropoietin (EPO), and reticulocytes (Rct) to bed rest and hypoxia. No significant differences were found in the mean ∆(Pre-Post) values of EPO across projects (LunHab, FemHab, and PlanHab; p>0.05), however, female EPO responses to NBR (Range - 17.39, IQR – 12.97 mIU.ml−1) and HBR (Range – 49.00, IQR – 10.91 mIU.ml−1) were larger than males (LunHab NBR Range – 4.60, IQR – 2.03; HBR Range – 7.10, IQR – 2.78; PlanHab NBR Range – 7.23, IQR – 1.37; HBR Range – 9.72, IQR – 4.91 mIU.ml−1). Bed rest duration had no impact on the heterogeneity of EPO, Rct, and RBC responses (10-d v 21-d). The resultant hematological changes that occur during NBR and HBR are not proportional to the acute EPO response. The following cascade of hematological responses to NBR and HBR suggests that the source of variability in the present data is due to mechanisms related to hypoxia as opposed to inactivity alone. Studies investigating hematological changes should structure their study design to explore these mechanistic responses and elucidate the discord between the EPO response and hematological cascade to fully assess heterogeneity.

Hematological and immunological responses to naturally occurring bovine respiratory disease in newly received beef calves in a commercial stocker farm.

The objective was to determine temporal changes in hematological and immune parameters in response to naturally occurring bovine respiratory disease (BRD) in commercially managed stocker calves. Forty newly weaned beef steers purchased from auction markets were housed at a commercial stocker operation in Crossville, TN. Blood samples, rectal temperature, and thoracic ultrasonography (TUS; 1: normal to 3: severe) were collected on days 0, 7, 14, and 21. Castration status (FC: freshly castrated; PC: previously castrated) was determined on arrival based on presence of a fresh castration site at the scrotum. Calves received antibiotics for BRD based on clinical severity scoring (CSS; 0: moribund, 4: moribund) and rectal temperature. Complete blood counts (CBC) were performed. Calves were categorized based on the number of treatments (NumTrt) received (0x, 1x, and 2x). Temporal variations in CBC and immune parameters were analyzed using mixed model repeated measure ANOVA (Proc GLIMMIX; SAS 9.4). Variation of CBCs and immune parameters based on TUS was determined using mixed model ANOVA. There was a NumTrt by day interaction effect on the responses of white blood cells (WBC) (P = 0.04) and haptoglobin (HPT) (P = 0.04). On day 21, WBC were greater in the 2x NumTrt group than other groups, but there were no differences in WBC between NumTrt levels on other days. Haptoglobin was greater in the 2x group on days 14 and 21 than 0x or 1x. Red blood cells (RBC) (P = 0.02) and WBC (P = 0.04) differed between FC and PC groups, and lower RBC and WBC were observed in the FC group. A castration status × day effect for mean corpuscular volume (MCV; P = 0.04) was observed where FC group had higher MCV at days 14 and 21 than the PC group. Tumor necrosis factor-α differed based on NumTrt (P = 0.03) and higher concentrations were found in 2x group. We observed a day effect for IL-1β (P = 0.009) and TNF-α (P = 0.001). Significant effect of TUS on HPT at day 14 (P = 0.0004) and day 21 (P = 0.002) was observed. Combining HPT and platelet explained 15% of the variability in treatment status on a given day, whereas HPT and hemoglobin explained 10% of the variability in lung consolidation status. Although hematological and immunological parameters varied largely in our study, the potential of combining HPT with hematological variables should be studied further. Results from this study would help in understanding temporal changes in CBC and immune parameters in newly received stocker cattle.

Predicting red blood cell response to mechanical loads

Red blood cells change shape during circulation in response to tensile and shear stress

CTIM-24. RANDOMIZED TRIAL OF NEOADJUVANT VACCINATION WITH TUMOR-CELL LYSATE INDUCES T CELL RESPONSE IN LOW-GRADE GLIOMAS

Abstract BACKGROUND The prognosis of WHO grade II low-grade gliomas (LGG) is varied with potential for long survival.Given their relatively intact immune system and slow growth rate, vaccines are an attractive treatment strategy for LGG in an attempt to defer more toxic treatments. The goals of this pilot study were to evaluate safety and immunological effects of vaccination with GBM6-AD, an allogeneic glioblastoma stem cell line lysate, with poly-ICLC in LGG. METHODS Eligible patients were ≥ 18 years old, ≥ 70 KPS, with recurrent LGG or imaging consistent with LGG, and amenable to resection. Patients were randomized to vaccine prior to surgery (Arm 1) or not (Arm 2) and all received adjuvant vaccine. Co-primary outcomes were safety and immune response in the tumor, with exploratory outcomes of survival and immunologic effects in peripheral blood. RESULTS A total of 17 eligible patients were evaluable – nine into Arm 1 and eight into Arm 2. Median age was 33 years, with median time from initial diagnosis of 4.7 years (0 – 20). Two patients (11.8%) previously received radiotherapy and seven (41.2%) prior systemic therapy. No dose limiting toxicities or grade 3 AEs were observed. Neoadjuvant vaccination induced up regulation of type-1 cytokines and chemokines in peripheral blood, and CD8+ T cell clones that reacted to the vaccine were also detected in the tumor. Median follow-up time from first post-operative vaccine was 20.8 months with median PFS of 11.0 months and time to change in therapy of 23.7 months. Of the six patients to receive additional treatment, three had second surgery only one confirming malignant progression to anaplastic oligodendroglioma. CONCLUSION Treatment was well-tolerated with no regimen-limiting toxicity. GBM6-AD plus poly-ICLC induced effector CD8+ T cell response in peripheral blood and enables some vaccine-reactive CD8+ T cells to migrate into the TME. Further investigation is warranted.

Diffusion-weighted MR spectroscopy (DW-MRS) is sensitive to LPS-induced changes in human glial morphometry: A preliminary study

BackgroundLow-dose lipopolysaccharide (LPS) is a well-established experimental method for inducing systemic inflammation and shown by microscopy to activate microglia in rodents. Currently, techniques for in-vivo imaging of glia in humans are limited to TSPO (Translocator protein) PET, which is expensive, methodologically challenging, and has poor cellular specificity. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) sensitizes MR spectra to diffusion of intracellular metabolites, potentially providing cell-specific information about cellular morphology. In this preliminary study, we applied DW-MRS to measure changes in the apparent diffusion coefficients (ADC) of glial and neuronal metabolites to healthy participants who underwent an LPS administration protocol. We hypothesized that the ADC of glial metabolites will be selectively modulated by LPS-induced glial activation. MethodsSeven healthy male volunteers, (mean 25.3 ± 5.9 years) were each tested in two separate sessions once after LPS (1 ng/Kg intravenously) and once after placebo (saline). Physiological responses were monitored during each session and serial blood samples and Profile of Mood States (POMS) completed to quantify white blood cell (WBC), cytokine and mood responses. DW-MRS data were acquired 5-5½ hours after injection from two brain regions: grey matter in the left thalamus, and frontal white matter. ResultsBody temperature, heart rate, WBC and inflammatory cytokines were significantly higher in the LPS compared to the placebo condition (p < 0.001). The ADC of the glial metabolite choline (tCho) was also significantly increased after LPS administration compared to placebo (p = 0.008) in the thalamus which scaled with LPS-induced changes in POMS total and negative mood (Adj R2 = 0.83; p = 0.004). ConclusionsDW-MRS may be a powerful new tool sensitive to glial cytomorphological changes in grey matter induced by systemic inflammation.

Peripheral white blood cell responses as emerging biomarkers for patient stratification and prognosis in acute spinal cord injury.

Purpose of reviewTo date, prognostication of patients after acute traumatic spinal cord injury (SCI) mostly relies on the neurological assessment of residual function attributed to lesion characteristics. With emerging treatment candidates awaiting to be tested in early clinical trials, there is a need for wholistic high-yield prognostic biomarkers that integrate both neurogenic and nonneurogenic SCI pathophysiology as well as premorbid patient characteristics.Recent findingsIt is becoming clearer that effective prognostication after acute SCI would benefit from integrating an assessment of pathophysiological changes on a systemic level, and with that, extend from a lesion-centric approach. Immunological markers mirror tissue injury as well as host immune function and are easily accessible through routine blood sampling. New studies have highlighted the value of circulating white blood cells, neutrophils and lymphocytes in particular, as prognostic systemic indicators of SCI severity and outcomes.SummaryWe survey recent advances in methods and approaches that may allow for a more refined diagnosis and better prognostication after acute SCI, discuss how these may help deepen our understanding of SCI pathophysiology, and be of use in clinical trials.