Circulating TNF-RII, IP-10 and HGF are associated with severity of COVID-19 in oncologic patients.

The COVID-19 patients showed hyperinflammatory response depending on the severity of the disease but little have been reported about this response in oncologic patients that also were infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sixty-five circulating cytokines/chemokines were quantified in 15 oncologic patients, just after SARS-CoV-2 infection and fourteen days later, and their levels were compared in patients who required hospitalisation by COVID-19 versus non-hospitalised patients. A higher median age of 72 years (range 61-83) in oncologic patients after SARS-CoV-2 infection was associated with hospitalisation requirement by COVID-19 versus a median age of 49 years (20-75) observed in the non-hospitalised oncologic patients (p = 0.008). Moreover, oncologic patients at metastatic stage or with lung cancer were significantly associated with hospitalisation by COVID-19 (p = 0.044). None of these hospitalised patients required ICU treatment. Higher basal levels of tumour necrosis factor receptor II (TNF-RII), interferon-γ (IFNγ)-induced protein 10 (IP-10) and hepatocyte growth factor (HGF) in plasma were significantly observed in oncologic patients who required hospitalisation by COVID-19. Higher TNF-RII, IP-10 and HGF levels after the SARS-CoV-2 infection in oncologic patients could be used as biomarkers of COVID-19 severity associated with hospitalisation requirements.

Point-of-care biomarker assay for rapid multiplexed detection of CRP and IP-10.

Rapid and accurate measurements of immune protein markers are essential for diagnosis and treatment in all clinical settings. The recent pandemic has revealed a stark need for developing new tools and assays that could be rapidly used in diverse settings and provide useful information to clinicians. Here, we describe the development and test application of a novel one-step CRP/IP-10 duplex assay for the LightDeck platform capable of delivering reproducible and accurate measurements in under eight minutes. We used the optimized assay to measure CRP and IP-10 levels in human blood and serum samples from healthy, SARS-CoV-2 (COVID-19) positive, and influenza-like illness (ILI) presenting patients. Our results agreed with previously published analyte levels and enabled us to make statistically significant comparisons relevant to multiple clinical parameters. Our duplex assay is a simple and powerful tool for aiding prognostic decision-making in diverse settings.

Predictive value of CXCL10 for the occurrence of immune-related adverse events in patient with renal cell carcinoma.

Immune checkpoint inhibitors (ICIs) have recently improved the prognosis of various cancers. By contrast, some immune-related adverse events (irAEs) caused by ICIs are fatal and have become problematic. The pathogenesis of irAEs remains unknown and must be elucidated to establish biomarkers. This study investigated plasma cytokine, chemokine, and anti-CD74 autoantibody levels in patients with renal cell carcinoma (RCC) and analyzed their association with irAEs. In a discovery cohort of 13 patients, plasma levels of chemokine (C-X-C motif) ligand (CXCL) 1, IL-17A, IL-1ß, IL-6, IL-8, CXCL10, MCP-1, and TNFα were measured at baseline and post-dose 1. Only CXCL10, at post-dose 1 but not at baseline, was significantly associated with grade 2 or higher irAEs (P = 0.0413). Plasma CXCL10 levels were then measured at baseline and post-dose 1 in an extended cohort of 43 patients with RCC who received ICI-based treatment. Higher plasma CXCL10 levels both at baseline and post-dose1 were significantly associated with the occurrence of grade 2 or higher irAEs (P = 0.0246 and 0.0137, respectively). Plasma CXCL13 levels, which we measured in a previous study, were significantly higher in patients with grade 2 or higher irAEs at baseline but not at post-dose 1 (P = 0.0037 and 0.052, respectively). No significant association between plasma anti-CD74 autoantibody level and both irAE pneumonitis and any grade 2 or higher irAE was observed. In conclusion, plasma CXCL10 is significantly associated with the occurrence of irAEs in patients with RCC treated with ICIs. CXCL10 is a potential predictive and on-treatment biomarker for irAEs.

CCL21 and IP10 as serum biomarkers for pulmonary involvement in systemic lupus erythematosus.

BACKGROUND: Although the significance of inflammatory cytokines and chemokines in the pathogenesis of SLE is well established, the findings showed diversity and implied that combining different biomarkers could be useful in monitoring disease activity or organ involvement. Despite the potentially high prevalence of lung involvement in SLE, only a few studies have investigated for lung biomarkers. OBJECTIVE: The aim of this study was to assess the value of Chemokine Ligand 21 (CCL 21) and Interferon gamma-induced protein 10 (IP10) as serum biomarkers for pulmonary involvement in SLE and their correlation with disease activity, organ involvement, pulmonary function tests (PFTs), and chest CT findings. MATERIALS AND METHODS: Sixty SLE patients and 30 age- and sex-matched controls were enrolled into this study. All patients underwent serological tests, PFTs, and chest CT examination. The serum levels of CCL21 and IP10 were analyzed, and their correlations with PFTs and CT were explored. RESULTS: SLE patients with pulmonary involvement had higher serum CCL21 and IP10 levels compared to those without pulmonary involvement which in turn had higher levels than the controls. There were strong negative correlations between CCL21 and IP10 and FEV1, FVC, and DLCO. There were also strong correlations between both biomarkers and HRCT and pulmonary damage, but no correlation with other disease manifestations. Serum level of 2095 pg/mL for CCL21 and 7185 pg/mL for IP10 could detect pulmonary involvement in SLE with a sensitivity of 83.7% and a specificity of 94.1%. Both biomarkers performed equally well in detecting SLE pulmonary involvement with a strong agreement between them (κ = 0.86, p < .001), but CCL21 was better correlated with PFT abnormalities. CONCLUSION: Both CCL21 and IP10 are serum biomarkers to detect pulmonary involvement in SLE with high sensitivity and specificity. CCL21 correlates better with PFT abnormalities.

Deciphering the Significance of Plasma Chemokines as Prognostic Biomarkers in Pegylated IFN-Α-2a /Ribavirin-Treated Chronic Hepatitis C Genotype 4 Patients.

BACKGROUND: Hepatitis C viral (HCV) infection is a major clinical burden globally. Pegylated IFN-α-2a (PEG-IFN-α-2a) with ribavirin (RIB) therapy induces an array of cellular antiviral responses, including dsRNA kinases (PKR), chemokines, and cytokines to tackle the HCV infection. However, many HCV patients develop resistance to PEG-IFN/RIB therapy rendering the therapy ineffective. OBJECTIVES: Here, we assess the significance of chemokines in response to PEG-IFN-α-2a with ribavirin (PEG-IFN/RIB) therapy. METHODS: Twenty patients with HCV infection and ten healthy controls were enrolled in this study and patients were categorized into two groups 1), HCV-Responder (HCV-R), and 2) HCV-non-responder (HCV-NR). We analyzed IP-10, MIG, MCP-1, EOTAXIN, RANTES, IL-8, MIP-1a, and MIP-1b by a magnetic bead-based multiplex immunoassay approach based on Luminex X-MAP multiplex technology, using a MAGPIX instrument (Luminex Corporation, USA). RESULTS: A significant elevation of ALT and AST enzymes was observed in HCV-NR. Besides, the PEG-IFN/RIB therapy in both MIG and MCP-1 in HCV-NR patients was significantly induced. PEGIFN/ RIB therapy significantly increased the levels of chemokines, such as IL-8, IP-10, EOTAXIN, MIG, RANTES, and MIP-1ß, in HCV-R, indicating the chemokine response to PEG-IFN/RIB therapy. CONCLUSION: Hence, MCP-1 and MIG could be the potential biomarkers in HCV-NR and might be associated with the development of liver fibrosis, liver failure, and hepatocellular carcinoma. LIMITATIONS: Our study has only twenty samples of PEG-IFN/RIB treated HCV patients. This might be the reason for the lack of association between some of the inflammatory markers evaluated and the SVR, therefore, the association found between the chemokine levels observed in the plasma of HCV-R and HCV-NR and EVR cannot be extrapolated to patients infected with other HCV genotypes.

Prognostic Markers in Hospitalized COVID-19 Patients: The Role of IP-10 and C-Reactive Protein.

BACKGROUND: SARS-CoV-2 is responsible for COVID-19, a clinically heterogeneous disease, ranging from being completely asymptomatic to life-threating manifestations. An unmet clinical need is the identification at disease onset or during its course of reliable biomarkers allowing patients' stratification according to disease severity. In this observational prospective cohort study, patients' immunologic and laboratory signatures were analyzed to identify independent predictors of unfavorable (either death or intensive care unit admission need) or favorable (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. METHODS: Between January and May 2021 (third wave of the pandemic), we enrolled 139 consecutive SARS-CoV-2 positive patients hospitalized in Northern Italy to study their immunological and laboratory signatures. Multiplex cytokine, chemokine, and growth factor analysis, along with routine laboratory tests, were performed at baseline and after 7 days of hospital stay. RESULTS: According to their baseline characteristics, the majority of our patients experienced a moderate to severe illness. At multivariate analysis, the only independent predictors of disease evolution were the serum concentrations of IP-10 (at baseline) and of C-reactive protein (CRP) after 7 days of hospitalization. Receiver-operating characteristic (ROC) curve analysis confirmed that baseline IP - 10 > 4271 pg/mL and CRP > 2.3 mg/dL at 7 days predict a worsening in clinical conditions (87% sensitivity, 66% specificity, area under the curve (AUC) 0.772, p < 0.001 and 83% sensitivity, 73% specificity, AUC 0.826, p < 0.001, respectively). CONCLUSIONS: According to our results, baseline IP-10 and CRP after 7 days of hospitalization could be useful in driving clinical decisions tailored to the expected disease trajectory in hospitalized COVID-19 patients.

Serum and urinary galectin-9 and C-X-C motif chemokine ligand 10.

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by a type I interferon (IFN) signature, and traditional methods for its measurement like gene expression analysis are cumbersome for routine use. Thus, we aimed to study galectin-9 as a biomarker and compared it with a validated marker, C-X-C motifchemokine ligand 10(CXCL-10). METHODS: Ninety-seven patients with SLE (26 years; 89 females) were included and stratified based on renal involvement and activity into - active (SLEDAI > 4) renal (35), active non-renal (32) and inactive renal subgroups (30) along with 20 healthy controls (HC, 25 years; 15 females). The median disease duration was 24 months (6-48), and SLEDAI 2K was 9 (2-15). Serum and urine galectin-9 and CXCL-10 levels were measured by ELISA. Urine levels were normalized with spot urine creatinine values. Follow-up serum and urine galectin-9 levels were measured for those in the active renal group at 6 months. RESULTS: Patients with SLE had higher serum galectin-9 (5.6 vs 1.7 µg/mL, p = .0001) but not urine galectin-9 (0.52 vs 0.32 µg, p = .7) levels as compared to HC. Serum galectin-9 but not urine galectin-9 was higher in patients with active as compared to inactive lupus (12.9 - active renal, 16.7 - active non-renal vs 3.57 µg/mL, p = .04 and .005). Serum CXCL-10 (0.16 vs 0.05, p = .01) and urine CXCL-10 (0 vs 0, p = .01) were both significantly higher in the SLE group as compared with HC. Serum but not urine CXCL-10 was higher in the active as compared to inactive lupus (0.2 - active renal, 0.3 - active non-renal vs 0.08 µg/mL, p = .9 and .02). Serum galectin-9 showed a modest correlation with CXCL-10 0.4 (0.2-0.6), whereas none was found between their urine levels.Serum galectin-9 and CXCL-10 showed a moderate positive correlation with SLEDAI 2K. Serum galectin-9 showed a greater AUC than CXCL-10 (0.77 vs 0.67) in differentiating active from inactive SLE, and both tested together had the best AUC of 0.82. However, urinary levels had no association with SLEDAI 2K or renal SLEDAI. In a subset of patients with active renal disease, serum galectin-9 but not urine levels declined significantly after 6 months. CONCLUSION: Serum galectin-9 is a good marker of lupus activity; however, it does not differentiate between active renal and active non-renal disease. It performs slightly better than CXCL-10. Urinary galectin-9 does not reflect renal activity.

Distinguishing Incubation and Acute Disease Stages of Mild-to-Moderate COVID-19.

While numerous studies have already compared the immune responses against SARS-CoV-2 in severely and mild-to-moderately ill COVID-19 patients, longitudinal trajectories are still scarce. We therefore set out to analyze serial blood samples from mild-to-moderately ill patients in order to define the immune landscapes for differently progressed disease stages. Twenty-two COVID-19 patients were subjected to consecutive venipuncture within seven days after diagnosis or admittance to hospital. Flow cytometry was performed to analyze peripheral blood immune cell compositions and their activation as were plasma levels of cytokines and SARS-CoV-2 specific immunoglobulins. Healthy donors served as controls. Integrating the kinetics of plasmablasts and SARS-CoV-2 specific antibodies allowed for the definition of three disease stages of early COVID-19. The incubation phase was characterized by a sharp increase in pro-inflammatory monocytes and terminally differentiated cytotoxic T cells. The latter correlated significantly with elevated concentrations of IP-10. Early acute infection featured a peak in PD-1+ cytotoxic T cells, plasmablasts and increasing titers of virus specific antibodies. During late acute infection, immature neutrophils were enriched, whereas all other parameters returned to baseline. Our findings will help to define landmarks that are indispensable for the refinement of new anti-viral and anti-inflammatory therapeutics, and may also inform clinicians to optimize treatment and prevent fatal outcomes.

STAT1 and CXCL10 involve in M1 macrophage polarization that may affect osteolysis and bone remodeling in extrapulmonary tuberculosis.

OBJECTIVE: This study was aimed to reveal the molecular mechanism of bone destruction due to macrophage polarization leading to during extrapulmonary tuberculosis (EPTB) infection. METHODS: The dataset GSE83456 was downloaded from the GEO database, and the xCell tool was used to obtain the 64 types of immune cells. The flow cytometry was performed to identified the differences between M1 and M2 macrophages between EPTB and the healthy controls (HCs). The enrichment analyses were performed on the differentially expressed genes (DEGs) and their functionally related modules. The hub genes were screened out, and their relationships with EPTB and the immune cell subtypes were further analyzed. RESULTS: The flow cytometric analysis validated this hypothesis of M1-macrophage polarization correlated with the pathogenesis of EPTB. Of the obtained 103 DEGs, 97 genes were upregulated, and 6 genes were downregulated. The GO and KEGG pathway analyses showed that the DEGs were particularly involved in the immune-related processes. The hub genes (STAT1 and CXCL10) might be involved in M1-macrophage polarization and correlated with the pathogenesis of EPTB. STAT1 and CXCL10 could also behave as biomarkers for EPTB. CONCLUSION: STAT1 and CXCL10 were involved in the M1-macrophage polarization and correlated with the pathogenesis of EPTB. Besides, both of them could also behave as biomarkers for EPTB diagnosis and provide the required clues for targeted therapy in the future.

Systemic CXCL10 is a predictive biomarker of vitiligo lesional skin infiltration, PUVA, NB-UVB and corticosteroid treatment response and outcome.

Vitiligo is an acquired pigmentary skin disorder that currently lacks standardized treatment and validated biomarkers to objectively evaluate disease state or therapeutic response. Although prior studies have linked vitiligo autoimmunity with CXCL10/CXCL9-mediated recruitment of leukocytes to the skin, only limited clinical data are available regarding CXCL10 as vitiligo biomarker. To evaluate the utility of systemic CXCL10 as a predictor of disease progression and treatment response on a large cohort of vitiligo patients. CXCL10 levels in lesional, perilesional, and unaffected skin of vitiligo patient (n = 30) and in the serum (n = 51) were measured by quantitative ELISA. CXCL10 expression, recruitment of leukocytes, and inflammatory infiltrates were evaluated by histochemical (n = 32) and immunofluorescence (n = 10) staining. Rigorous cross-sectional and longitudinal biostatistical analysis were employed to correlate CXCL10 levels with disease variables, treatment response, and outcome. We demonstrated that elevated CXCL10 level (2 pg/mm2 and higher) in lesional skin correlates with increased leukocytic infiltrate, disease duration (< 2 year), and its higher level in the serum (50 pg/ml and higher). Changes in CXCL10 serum levels in patients treated with psoralen plus UVA (PUVA) phototherapy, narrowband UVB (NB-UVB) phototherapy, and systemic steroids (SS) correlated with changes in the intralesional CXCL10 levels in repigmented skin. NB-UVB and SS regimens provided most consistent CXCL10 mean change, suggesting that these regimens are most effective in harnessing CXCR3-mediated inflammatory response. Serum CXCL10 is a useful vitiligo biomarker, which predicts lesional skin leukocytic infiltration, and vitiligo treatment response and outcome.

Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks.

The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 in acute disease (n = 58) and in disease recovery in convalescent patients (n = 28) from Hannover Medical School, we used flow cytometry and proteomics data with unsupervised clustering analyses. In our observational study, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity.

[Effect of chemokines CXCL9 and CXCL10 on bone erosion in patients with rheumatoid arthritis].

OBJECTIVE: To detect the serum level of soluble chemokines CXCL9 and CXCL10 in patients with rheumatoid arthritis (RA), and to analyze their correlation with bone erosion, as well as the clinical significance in RA. METHODS: In the study, 105 cases of RA patients, 90 osteoarthritis (OA) patients and 25 healthy controls in Peking University People's Hospital were included. All the clinical information of the patients was collected, and the serum CXCL9 and CXCL10 levels of both patients and healthy controls were measured by enzyme-linked immune sorbent assay (ELISA). CXCL9 and CXCL10 levels among different groups were compared. The correlation between serum levels with clinical/laboratory parameters and the occurrence of bone erosion in RA were analyzed. Independent sample t test, Chi square test, Mann-Whitney U test, Spearman's rank correlation and Logistic regression were used for statistical analysis. RESULTS: The levels of CXCL9 and CXCL10 were significantly higher in the RA patients [250.02 (126.98, 484.29) ng/L, 108.43 (55.16, 197.17) ng/L] than in the OA patients [165.05 (75.89, 266.37) ng/L, 69.00 (33.25, 104.74) ng/L] and the health controls [79.47 (38.22, 140.63) ng/L, 55.44 (18.76, 95.86) ng/L] (all P < 0.01). Spearman's correlation analysis showed that the level of serum CXCL9 was positively correlated with swollen joints (SJC), rheumatoid factor (RF) and disease activity score 28 (DAS28) (r=0.302, 0.285, 0.289; P=0.009, 0.015, 0.013). The level of serum CXCL10 was positively correlated with tender joints (TJC), SJC, C-reactive protein (CRP), immunoglobulin (Ig) A, IgM, RF, anti-cyclic citrullinated peptide antibody (ACPA), and DAS28 (r=0.339, 0.402, 0.269, 0.266, 0.345, 0.570, 0.540, 0.364; P=0.010, 0.002, 0.043, 0.045, 0.009, < 0.001, < 0.001, 0.006). Serum CXCL9 and CXCL10 levels in the RA patients with bone erosion were extremely higher than those without bone erosion [306.84 (234.02, 460.55) ng/L vs. 149.90 (75.88, 257.72) ng/L, 153.74 (89.50, 209.59) ng/L vs. 54.53 (26.30, 83.69) ng/L, respectively] (all P < 0.01). Logistic regression analysis showed that disease duration, DAS28 and serum level of CXCL9 were correlated with bone erosion in the RA patients (P < 0.05). CONCLUSION: Serum levels of CXCL9 and CXCL10 were remarkably elevated in patients with RA, and correlated with disease activities and occurrence of bone erosion. Chemokines CXCL9 and CXCL10 might be involved in the pathogenesis and bone destruction in RA.

Candidate Biomarkers to Distinguish Spinal Tuberculosis From Mechanical Back Pain in a Tuberculosis Endemic Setting.

Background: Spinal tuberculosis (TB) may have a variable, non-specific presentation including back pain with- or without- constitutional symptoms. Further tools are needed to aid early diagnosis of this potentially severe form of TB and immunological biomarkers may show potential in this regard. The aim of this study was to investigate the utility of host serum biomarkers to distinguish spinal TB from mechanical back pain. Methods: Patients with suspected spinal TB or suspected mechanical back pain were recruited from a tertiary hospital in the Western Cape, South Africa, and provided a blood sample for biomarker analysis. Diagnosis was subsequently confirmed using bacteriological testing, advanced imaging and/or clinical evaluation, as appropriate. The concentrations of 19 host biomarkers were evaluated in serum samples using the Luminex platform. Receiver Operating Characteristic (ROC) curves and General Discriminant Analysis were used to identify biomarkers with the potential to distinguish spinal TB from mechanical back pain. Results: Twenty-six patients with spinal TB and 17 with mechanical back pain were recruited. Seven out of 19 biomarkers were significantly different between groups, of which Fibrinogen, CRP, IFN-γ and NCAM were the individual markers with the highest discrimination utility (Area Under Curve ROC plot 0.88-0.99). A five-marker biosignature (CRP, NCAM, Ferritin, CXCL8 and GDF-15) correctly classified all study participants after leave-one-out cross-validation. Conclusion: This study identified host serum biomarkers with the potential to diagnose spinal TB, including a five-marker biosignature. These preliminary findings require validation in larger studies.

Serial measurement of cytokines strongly predict COVID-19 outcome.

PURPOSE: Cytokines are major mediators of COVID-19 pathogenesis and several of them are already being regarded as predictive markers for the clinical course and outcome of COVID-19 cases. A major pitfall of many COVID-19 cytokine studies is the lack of a benchmark sampling timing. Since cytokines and their relative change during an infectious disease course is quite dynamic, we evaluated the predictive value of serially measured cytokines for COVID-19 cases. METHODS: In this single-center, prospective study, a broad spectrum of cytokines were determined by multiplex ELISA assay in samples collected at admission and at the third day of hospitalization. Appropriateness of cytokine levels in predicting mortality were assessed by receiver-operating characteristic (ROC) analyses for both sampling times in paralel to conventional biomarkers. RESULTS: At both sampling points, higher levels of IL-6, IL-7, IL-10, IL-15, IL-27 IP-10, MCP-1, and GCSF were found to be more predictive for mortality (p<0.05). Some of these cytokines, such as IL-6, IL-10, IL-7 and GCSF, had higher sensitivity and specificity in predicting mortality. AUC values of IL-6, IL-10, IL-7 and GCSF were 0.85 (0.65 to 0.92), 0.88 (0.73 to 0.96), 0.80 (0.63 to 0.91) and 0.86 (0.70 to 0.95), respectively at hospital admission. Compared to hospital admission, on the 3rd day of hospitalization serum levels of IL-6 and, IL-10 decreased significantly in the survivor group, unlike the non-survivor group (IL-6, p = 0.015, and IL-10, p = 0.016). CONCLUSION: Our study results suggest that single-sample-based cytokine analyzes can be misleading and that cytokine levels measured serially at different sampling times provide a more precise and accurate estimate for the outcome of COVID-19 patients.

CXCL1, CXCL10 and CXCL12 Chemokines are Variously Expressed in Acute Myeloid Leukemia Patients Prior and Post Bone Marrow Transplantation.

AIM: The chemokine-receptor axes play parts in development of leukemia, CXCL1, CXCL10 and CXCL12 are involved in immune responses. Thus, we have examined the serum levels of these chemokines in parallel with their related cognate receptors (CXCR1, CXCR3 and CXCR4) in AML (acute myeloid leukemia) patients prior and post BMT (bone marrow transplantation) therapy. MAIN METHODS: Clinical specimens were collected from 46 AML patients (23 M1 and 23 M3 subtypes) before/after BMT. CXCL1, CXCL10 and CXCL12 concentrations were determined by ELISA. The mRNA levels of the related receptors were detected by QRT_PCR. Data were analyzed by T-test, χ2 and ANOVA statistical methods in SPSS software version 18. A difference was regarded significant if P value < 0.05. KEY FINDINGS: Our results indicated that the elevated levels of CXCL12 in AML patients were remained unchanged after transplantation.  The CXCL10 concentration was decreased in patients. All studied chemokines were elevated in BMT patients with history of 9 times PLT transfusion. In patients who received BMT from siblings CXCL1 and CXCL10 have been elevated, whereby they were compared to patients who received BMT from parents while CXCL12 sustained unchanged in groups. Serum measures of CXCL1 and CXCL10 were induced in acute and chronic GVHD patients in compare to these without GVHD. SIGNIFICANCE: According to the results, it can be concluded that these chemokines play fundamental parts in pathogenesis of both AML and BMT. It is worthy to note that chemokines could be used as diagnostic markers alongside with possible promising therapeutic targets.

Neurofilament Light in CSF and Plasma Is a Marker of Neuronal Damage in HTLV-1-Associated Myelopathy and Correlates With Neuroinflammation.

BACKGROUND AND OBJECTIVES: To evaluate the usefulness of CSF and plasma neurofilament light (Nf-L) as a biomarker for human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM). METHODS: Nf-L, CXCL10, and neopterin were measured by ELISA in 83 CSF samples obtained from 49 individuals living with HTLV-1/2. Plasma Nf-L was also measured by single molecule array. Results were correlated with duration of disease, age, mobility, CSF cell counts, CSF protein, and HTLV-1 proviral load. RESULTS: Nf-L was detected in all CSF samples (median [range] = 575 [791.8-2,349] pg/mL) and positively correlated with markers of inflammation (CXCL10 (r = 0.733), neopterin (r = 0.499), cell count (r = 0.403), and protein levels (r = 0.693) in CSF; p < 0.0015). There was an inverse correlation between Nf-L and duration of disease (r = -0.584, p < 0.0001). Wheelchair-dependent patients had high concentrations of markers of inflammation and neuronal damage. Concentrations of CXCL10, neopterin, and Nf-L remained elevated in follow-up samples (mean follow-up 5.2 years). Nf-L in plasma correlated with concentration of Nf-L, neopterin, CXCL10, and protein in CSF. CONCLUSIONS: Nf-L in plasma and CSF has potential to be used as a biomarker of disease activity in HAM. Neuronal damage seems to be more intense early in disease but persists long term. Wheelchair-dependent patients have ongoing neuroinflammation.

CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study.

BACKGROUND: Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. METHODS: We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. RESULTS: Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233-0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547-0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. CONCLUSIONS: CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19.

Serum Biomarker Profile Including CCL1, CXCL10, VEGF, and Adenosine Deaminase Activity Distinguishes Active From Remotely Acquired Latent Tuberculosis.

Introduction: There is an urgent medical need to differentiate active tuberculosis (ATB) from latent tuberculosis infection (LTBI) and prevent undertreatment and overtreatment. The aim of this study was to identify biomarker profiles that may support the differentiation between ATB and LTBI and to validate these signatures. Materials and Methods: The discovery cohort included adult individuals classified in four groups: ATB (n = 20), LTBI without prophylaxis (untreated LTBI; n = 20), LTBI after completion of prophylaxis (treated LTBI; n = 20), and healthy controls (HC; n = 20). Their sera were analyzed for 40 cytokines/chemokines and activity of adenosine deaminase (ADA) isozymes. A prediction model was designed to differentiate ATB from untreated LTBI using sparse partial least squares (sPLS) and logistic regression analyses. Serum samples of two independent cohorts (national and international) were used for validation. Results: sPLS regression analyses identified C-C motif chemokine ligand 1 (CCL1), C-reactive protein (CRP), C-X-C motif chemokine ligand 10 (CXCL10), and vascular endothelial growth factor (VEGF) as the most discriminating biomarkers. These markers and ADA(2) activity were significantly increased in ATB compared to untreated LTBI (p ≤ 0.007). Combining CCL1, CXCL10, VEGF, and ADA2 activity yielded a sensitivity and specificity of 95% and 90%, respectively, in differentiating ATB from untreated LTBI. These findings were confirmed in the validation cohort including remotely acquired untreated LTBI participants. Conclusion: The biomarker signature of CCL1, CXCL10, VEGF, and ADA2 activity provides a promising tool for differentiating patients with ATB from non-treated LTBI individuals.

The role of CXCL10 in prognosis of patients with colon cancer and tumor microenvironment remodeling.

BACKGROUNG: Tumor microenvironment (TME) has gradually emerged as an important research topic in the fight against cancer. The immune system is a major contributing factor in TME, and investigations have revealed that tumors are partially infiltrated with numerous immune cell subsets. METHOD: We obtained transcriptome RNA-seq data from the the Cancer Genome Atlas databases for 521 patients with colon adenocarcinoma (COAD). ESTIMATE algorithms are then used to estimate the fraction of stromal and immune cells in COAD samples. RESULT: A total of 1109 stromal-immune score-related differentially expressed genes were identified and used to generate a high-confidence protein-protein interaction network and univariate COX regression analysis. C-X-C motif chemokine 10 (CXCL10) was identified as the core gene by intersection analysis of data from protein-protein interaction network and univariate COX regression analysis. Then, for CXCL10, we performed gene set enrichment analysis, survival analysis and clinical analysis, and we used CIBERSORT algorithms to estimate the proportion of tumor-infiltrating immune cells in COAD samples. CONCLUSION: We discovered that CXCL10 levels could be effective for predicting the prognosis of COAD patients as well as a clue that the status of TME is transitioning from immunological to metabolic activity, which provided additional information for COAD therapies.