Clinical characteristics and changes in serum CXCL10 and CXCL16 levels in patients with severe mycoplasma pneumonia.

To explore the clinical characteristics and changes in serum CXCL10 and CXCL16 in patients with severe mycoplasma pneumonia, and to analyze the risk factors of severe mycoplasma pneumonia. About 258 children with acute mycoplasma pneumoniae pneumonia (MPP) admitted to the respiratory department of a certain hospital from January 2020 to December 2022 were selected as the study subjects. According to the severity of MPP, patients are divided into 2 groups, namely the mild illness group (Q group) and the severe illness group (Z group). The number of cases in these 2 groups of children is 167 and 91, respectively. The serum CXCL10, CXCL16, and other indicators of 2 groups are tested. Compared to group Q, patients in group Z have a higher proportion of extrapulmonary complications, longer cough time, longer shortness of breath, and longer wheezing time (P < .05). The serum CXCL16 is higher and the proportion of pleural effusion is higher (P < .01). There are more cases of fever, longer fever duration, longer hospital stay, higher serum CXCL10, and higher D-dimer levels (P < .001). The area under the curve of the probability curve for predicting severe mycoplasma pneumonia is 0.975 (P < .05). Children with severe mycoplasma pneumonia have significantly longer fever duration and hospital stay than those with mild symptoms. The serum levels of CXCL10 and CXCL16 are significantly elevated.

Elevated plasma levels of CXCL16 in severe COVID-19 patients.

Genome-wide association studies have recently identified 3p21.31, with lead variant pointing to the CXCR6 gene, as the strongest thus far reported susceptibility risk locus for severe manifestation of COVID-19. In order the determine its role, we measured plasma levels of Chemokine (C-X-C motif) ligand 16 (CXCL16) in the plasma of COVID-19 hospitalized patients. CXCL16 interacts with CXCR6 promoting chemotaxis or cell adhesion. The CXCR6/CXCL16 axis mediates homing of T cells to the lungs in disease and hyper-expression is associated with localised cellular injury. To characterize the CXCR6/CXCL16 axis in the pathogenesis of severe COVID-19, plasma concentrations of CXCL16 collected at baseline from 115 hospitalized COVID-19 patients participating in ODYSSEY COVID-19 clinical trial were assessed together with a set of controls. We report elevated levels of CXCL16 in a cohort of COVID-19 hospitalized patients. Specifically, we report significant elevation of CXCL16 plasma levels in association with severity of COVID-19 (as defined by WHO scale) (P-value < 0.02). Our current study is the largest thus far study reporting CXCL16 levels in COVID-19 hospitalized patients (with whole-genome sequencing data available). The results further support the significant role of the CXCR6/CXCL16 axis in the immunopathogenesis of severe COVID-19 and warrants further studies to understand which patients would benefit most from targeted treatments.

Clinical and biological markers for predicting ARDS and outcome in septic patients.

Sepsis is a common cause of acute respiratory distress syndrome (ARDS) associated with a high mortality. A panel of biomarkers (BMs) to identify septic patients at risk for developing ARDS, or at high risk of death, would be of interest for selecting patients for therapeutic trials, which could improve ARDS diagnosis and treatment, and survival chances in sepsis and ARDS. We measured nine protein BMs by ELISA in serum from 232 adult septic patients at diagnosis (152 required invasive mechanical ventilation and 72 had ARDS). A panel including the BMs RAGE, CXCL16 and Ang-2, plus PaO2/FiO2, was good in predicting ARDS (area under the curve = 0.88 in total septic patients). Best performing panels for ICU death are related to the presence of ARDS, need for invasive mechanical ventilation, and pulmonary/extrapulmonary origin of sepsis. In all cases, the use of BMs improved the prediction by clinical markers. Our study confirms the relevance of RAGE, Ang-2, IL-1RA and SP-D, and is novel supporting the inclusion of CXCL16, in BMs panels for predicting ARDS diagnosis and ARDS and sepsis outcome.

C-X-C Motif Chemokine Ligand 16 Is a Potent Predictor of Outcomes in Dialysis Patients.

INTRODUCTION: C-X-C motif chemokine ligand 16 (CXCL16) is an inflammatory marker that has been found to be predictive of outcomes in patients with cardiovascular disease. Our previous work has also demonstrated its relation to cardiac injury in dialysis patients. However, it is yet unclear whether there is an association between CXCL16 and adverse outcomes in dialysis patients. We aimed to evaluate its prognostic value along with several traditional inflammatory markers in the current study. METHODS: This is a multicenter longitudinal study of prevalent dialysis patients. Circulating inflammatory markers including CXCL16, C-reactive protein (CRP), tumor necrosis factor-α, and interleukin-6 (IL-6) were measured using a multiplex assay. The primary outcomes were all-cause mortality and a composite of major adverse cardiovascular events (MACEs). The associations between biomarkers and outcomes were analyzed using Cox proportional hazards regression models. RESULTS: Of the 366 participants with available plasma samples, the average age was 52.5 (±12.1) years, and there were 160 (43.7%) female participants. For all-cause mortality, logarithmically transformed CXCL16, IL-6, and CRP were independent predictors after adjustment for covariates. When the 3 markers were included in the same model, CXCL16 was the only one remaining its significance. For MACEs, logarithmically transformed CXCL16 and IL-6 were significant predictors when analyzed separately and CXCL16 was an independent predictor even after adjustment for IL-6. When the biomarkers were analyzed as categorical variables, only CXCL16 was associated with both outcomes. Adding CXCL16 to established risk factors improved risk prediction as revealed by Net Reclassification Index (NRI). CONCLUSION: Using a multimarker approach, we determined that CXCL16 is a potent predictor of all-cause mortality and cardiovascular events in dialysis patients. Our data suggest CXCL16 may improve risk stratification and could be a potential interventional target.

Fatty Acid-Binding Protein 3 and CXC-Chemokine Ligand 16 are Associated with Unfavorable Outcome in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with activation of the inflammatory cascade contributing to unfavorable outcome and secondary complications, such as delayed cerebral ischemia (DCI). Both fatty acid-binding protein 3 (FABP3) and CXC-chemokine ligand 16 (CXCL-16) have been linked to vascular inflammation and cellular death. The authors aimed to assess the 30-day prognostic value of serum levels of FABP3 and CXCL-16 and explore their associations with DCI in aSAH patients. METHODS: A total of 60 patients with aSAH were prospectively enrolled. Sampling for markers was done at 24 hours after the index event. FABP3 and CXCL-16 serum concentrations were determined by MilliPlex multiplex immunoassay method. The primary endpoint was unfavorable outcome at Day 30 based on the modified Rankin Scale. RESULTS: Both FABP3 and CXCL-16 levels were significantly elevated in patients with unfavorable outcome compared to those with favorable outcome after aSAH (FABP3: 2133 pg/mL, IQR: 1053-4567 vs. 3773, 3295-13116; p<0.003 and CXCL-16: 384 pg/mL, 313-502 vs. 498, 456-62, p<0.001). The area under the curve (AUC) for serum CXCL-16 levels as a predictor of unfavorable outcome at Day 30 was 0.747 (95% CI =0.622-0.871; p<0.001). Based on binary logistic regression analysis, serum CXCL-16 with a cut-off level >446.7 ng/L independently predicted Day 30 unfavorable outcome with a sensitivity of 81% and a specificity of 62%. Neither CXCL-16 nor FABP3 showed a significant correlation with DCI. CONCLUSION: Early FABP3 and CXCL-16 levels are significantly associated with poor 30-day outcome in patients with aSAH.

Evaluation of serum CXC chemokine ligand 16 (CXCL16) as a novel inflammatory bio- marker or familial Mediterranean fever disease

Background/aim: Familial Mediterranean fever (FMF) is a disease that is mainly diagnosed with clinical features. Several well- known inflammatory markers increase in FMF. However, there is still a need for diagnostic tests for specifying FMF and monitoring inflammatory activity. CXCL16 is a chemokine produced by inflammatory cells that demonstrate efficacy in the acute phase response. In this study, we aimed to investigate the relationship between CXCL16 levels and FMF disease and to evaluate CXCL16 levels as a novel biomarker for FMF. Materials and methods: Fifty-three male patients diagnosed with FMF and sixty healthy individuals were included in this cross- sectional study. Blood samples were taken in the first 24 h of the attack periods. Serum soluble CXCL16 was evaluated by enzyme-linked immunosorbent assay (ELISA) method. Results: CXCL16 (P < 0.001), erythrocyte sedimentation rate (P < 0.001), C-reactive protein (P < 0.001), and fibrinogen (P = 0.005) were significantly higher in FMF group than in control group. Receiver operating characteristic (ROC) curve analysis revealed a cut off value of CXCL16 as 2.68 ng/ml with 83% sensitivity and 68% specificity (P < 0.001). Logistic regression analysis indicated that high CXCL16 and erythrocyte sedimentation rate levels were predictive parameters for FMF disease (OR 8.31; 95% CI 2.59-26.62; p <0.001) (OR 1.27; 95% CI 1.12-1.44; P < 0.001). There was no correlation between CXCL16 levels and attack frequency and disease duration (P = 0.395, P = 0.956). Conclusion: To the best of our knowledge, this is the first study evaluating serum soluble CXCL16 levels as a biomarker for FMF. CXCL16 levels were significantly higher and were predictive for monitoring inflammatory activity in patients with FMF. CXCL16 may be a promising biomarker for FMF diagnosis.

Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease leading to considerable disability over time. The disease can be characterized by the presence of multiple autoantibodies in the serum and synovial fluid. Microbial dysbiosis is proposed to play a role in the pathogenesis of RA. Increased systemic bacterial exposure leads to elevated levels of antimicrobial response factors (ARFs) in the circulation. In the present study, we tested whether RA patients have increased levels of ARFs by analyzing the levels of multiple ARFs in serum from RA patients and healthy age and sex-matched controls. The levels of soluble CD14 (sCD14), lysozyme, and CXCL16 were significantly elevated in RA patients compared to healthy controls. Lipopolysaccharide binding protein (LBP) levels remained unchanged in RA patients compared to healthy controls. A positive correlation of LBP with rheumatoid factor (RF) was also found in RA subjects. Interestingly, the levels of anti-endotoxin core antibodies (EndoCAb) IgM, total IgM, EndoCAb IgA, and total IgA were significantly elevated in RA patients compared to healthy controls. No significant changes in the levels of EndoCAb IgG and total IgG were observed in RA patients compared to healthy controls. Furthermore, lysozyme and CXCL16 levels were positively correlated with disease severity among RA subjects. Increases in the levels of several ARFs and their correlations with clinical indices suggest systemic microbial exposure in the RA cohort. Modulation of microbial exposure may play an important role in disease pathogenesis in individuals with RA.

The clinical significance of CXCL16 in the treatment of advanced non-small cell lung cancer.

BACKGROUND: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF)-A, has shown efficacy in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). There are no identified or clinically validated biomarkers to determine the efficacy of bevacizumab. In this study, we assessed the adequacy of chemokine (C-X-C motif) ligand 16 (CXCL16) as a biomarker for patients treated with bevacizumab-containing chemotherapy regimen. METHODS: Patients diagnosed histologically with NSCLC were enrolled. Serial serum CXCL16 levels during treatment were measured by enzyme-linked immunosorbent assay. The relationship between serum CXCL16 levels before and after treatment, progression-free survival, and overall survival were analyzed. CXCL16 and VEGF-A expressions in lung cancer tissue were also evaluated by immunohistochemical tests. RESULTS: The median serum level of CXCL16 in these patients was 3.4 ng/mL, which was significantly higher than that in age-matched healthy adults (2.2 ng/mL). Immunohistochemistry results showed that CXCL16 was predominantly localized in the tumor stroma, whereas VEGF was expressed in tumor cells. Including bevacizumab with chemotherapy led to lower CXCL16 levels post-chemotherapy, which correlated with better response rates. In addition, evaluation of differences in serum CXCL16 levels before and after the first-line chemotherapy showed that longer overall survival was achieved in patients who showed a larger decrease in serum CXCL16 levels. CONCLUSIONS: According to our findings, serum CXCL16 level was identified as a potential biomarker for the efficacy of therapy, including anti-VEGF. KEY POINTS: Significant findings of the study Patients with NSCLC whose serum CXCL16 levels decreased below 0.07 ng/mL after chemotherapy, showed longer overall survival than those without this decrease. Moreover, low CXCL16 levels corresponded to better response rates among patients with advanced NSCLC treated with bevacizumab-containing chemotherapy. What this study adds Previously there were no identifiable predictive biomarkers to determine the efficacy of bevacizumab. Data from our findings identified serum CXCL16 level as a potential biomarker for the efficacy of bevacizumab-containing chemotherapy.

C-X-C Ligand 16 Is an Independent Predictor of Cardiovascular Death and Morbidity in Acute Coronary Syndromes.

OBJECTIVE: The chemokine CXCL16 (C-X-C motif ligand 16) is a scavenger receptor for OxLDL (oxidized low-density lipoproteins) and involved in inflammation at sites of atherosclerosis. This study aimed to investigate the association of CXCL16 with clinical outcome in patients with acute coronary syndrome. Approach and Results: Serial measurements of CXCL16 were performed in a subgroup of 5142 patients randomized in the PLATO trial (Platelet Inhibition and Patient Outcome). Associations between CXCL16 and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and the individual components were assessed by multivariable Cox regression analyses. The hazard ratio per 50% increase in admission levels of CXCL16 analyzed as continuous variable was 1.64 (95% CI, 1.44-1.88), P<0.0001. This association remained statistically significant after adjustment for randomized treatment, clinical variables, CRP (C-reactive protein), leukocytes, cystatin C, NT-proBNP (N-terminal pro-brain natriuretic peptide), troponin T, GDF-15 (growth differentiation factor 15), and other biomarkers; hazard ratio 1.23 (1.05-1.45), P=0.0126. The admission level of CXCL16 was independently associated with cardiovascular death (1.50 [1.17-1.92], P=0.0014) but not with ischemic events alone, in fully adjusted analyses. No statistically independent association was found between CXCL16 measured at 1 month, or change in CXCL16 from admission to 1 month, and clinical outcomes. CONCLUSIONS: In patients with acute coronary syndrome, admission level of CXCL16 is independently related to adverse clinical outcomes, mainly driven by an association to cardiovascular death. Thus, CXCL16 measurement may enhance risk stratification in patients with this condition. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

CXCL16 Induces the Progression of Pulmonary Fibrosis through Promoting the Phosphorylation of STAT3.

Aim: The transmembrane chemokine (C-X-C motif) ligand 16 (CXCL16) plays a vital role in the pathogenesis of organ fibrosis, including the liver and kidney. However, the detailed biological function of CXCL16 is still not fully understood in the progression of pulmonary fibrosis (PF). The aim of present study is to examine the function of CXCL16 in PF. Materials and Methods: In this study, we constructed the PF model on mouse by using bleomycin and analyzed the effect of the mouse recombinant protein CXCL16 on mouse lung fibroblast L929 (LF) as well. To further examine the connection between CXCL16 and STAT3 in mouse LF cells, the STAT3 inhibitor AG490 was utilized to inhibit the expression of STAT3. Meanwhile, lipopolysaccharide was used to enhance the phosphorylation of STAT3 (p-STAT3) in mouse LF cells. Results: Our results indicated that the level of CXCL16/CXCR6 was significantly upregulated in the mouse PF model. Moreover, the level of p-STAT3 was also promoted. In addition, the mouse recombinant protein CXCL16 not only contributed to the proliferation of mouse LF cells but also induced the expression of p-STAT3 in LF cells. However, the effect of CXCL16 was deeply abolished by the STAT3 inhibitor AG490 in LF cells. Meanwhile, the antibody of CXCL16 deeply reduced the phosphorylation of STAT3 in lipopolysaccharide (LPS) cultured cells. Conclusions: All these results demonstrated that CXCL16 promoted the phosphorylation of STAT3 and further demonstrated that STAT3 was a critical component in CXCL16/CXCR6 signaling pathway. This research not only enhanced the comprehension of CXCL16 but also indicated its potential value as a target in the treatment for human PF.

CXCL16/CXCR6-mediated adhesion of human peripheral blood mononuclear cells to inflamed endothelium.

The endothelial chemokine CXC motif ligand 16 (CXCL16) is involved in the recruitment and firm adhesion of CXCR6+ cells to the atherosclerosis-prone aortic vessel wall. Recently we showed that CXCR6+ platelets from flowing blood attach to CXCL16 expressed by activated endothelium on the luminal side of the blood vessel. With this study we supplement these findings with the observation that platelets bound to the inflamed endothelium are presenting CXCR6 to CXCL16-positive peripheral blood mononuclear cells (PBMCs) and, thus, are mediating an increased adhesion of PBMCs to the arterial wall. Furthermore we identified endothelial CXCL16 as an important adhesion molecule promoting the firm adhesion of CXCR6-positive PBMCs to inflamed endothelium. Our results demonstrate that endothelial CXCL16 as well as platelet CXCR6 are acting as potent PBMC-adhesion ligands, inducing PBMC-adhesion to the atherosclerosis-prone vessel wall and thus promoting the progression of atherosclerosis.

Decreased Systemic Levels of Endocan-1 and CXCL16 in Psoriasis Are Restored following Narrowband UVB Treatment.

BACKGROUND: In psoriasis, a common immune-mediated disease affecting 2-3% of the population worldwide, there is an increased prevalence of extracutaneous diseases including obesity, the metabolic syndrome, and cardiovascular disease. This is believed to be linked to systemic inflammation. In previous studies, we have explored various markers in plasma and serum to characterize the ongoing systemic inflammation in psoriasis patients compared to controls. We have identified several markers that were altered in psoriasis patients, but which all were unresponsive to narrowband UVB (NB-UVB) treatment. OBJECTIVE: The objective of the study was to evaluate the effect of NB-UVB treatment on markers of cardiovascular risk and systemic inflammation in psoriasis. METHODS: The levels of 17 potential biomarkers with an association with cardiovascular risk were quantitated in plasma from 37 age- and gender-matched psoriasis patients and controls at baseline and in 21 psoriasis patients after 12 weeks of NB-UVB treatment to identify a systemic treatment response. RESULTS: We identified the mediators endocan-1, CXCL16, and sVEGFR1, which were systemically decreased in psoriasis at baseline, as well as FABP3, FABP4, and sIL-1R1, which showed normal baseline levels. After 10-12 weeks of NB-UVB treatment, endocan-1 and CXCL16 were restored to normal levels, while sVEGFR1, FABP3, FABP4, and sIL-1R1 showed a significant reduction. CONCLUSION: The current study expands the number of potential biomarkers in psoriasis by including a greater number and variety of mediators, approaching the systemic inflammation from additional vantage points, including soluble immune receptors and adipocyte contribution, to provide a more complete picture of the systemic inflammatory state in psoriasis.

CXC Motif Ligand 16 Promotes Nonalcoholic Fatty Liver Disease Progression via Hepatocyte-Stellate Cell Crosstalk.

Context: Nonalcoholic fatty liver disease (NAFLD) is a focus of attention because of its prevalence. CXC motif ligand 16 (CXCL16) has been studied in inflammatory and metabolic diseases. Objective: To investigate the role of CXCL16 in steatosis and fibrosis in patients with NAFLD. Design: Liver specimens and sera of patients with NAFLD were collected from 2012 to 2017. Setting: Beijing 302 Hospital. Participants: 117 patients with NAFLD and 15 healthy controls. Interventions: None. Main Outcome Measures: The main outcome measures were CXCL16 levels in sera and biopsy specimens of patients with NAFLD. Results: CXCL16 serum level was markedly elevated in patients with NAFLD, especially in those at the S3 steatosis level according to the steatosis, activity, and fibrosis (SAF) scoring system. The different serum levels of CXCL16 between groups were due to data in patients with A or F scores ≥2, according to the SAF scoring system. CXCL16 accumulated around steatotic hepatocytes in biopsy specimens. In vitro, CXCL16 treatment led to severe steatosis of hepatocytes in the hepatocyte-stellate cell coculture system and suppressed the respiration rate of hepatocytes. Lipogenic gene expression and hepatic stellate cell activation indexes were increased in a CXCL16 overexpression system. In addition, ligands in the Hedgehog pathway cascade were downregulated in hepatocytes. Conclusions: CXCL16 was highly expressed in patients with NAFLD, suggesting that it may contribute to steatotic and fibrotic progression. CXCL16 may be a potential noninvasive marker of NAFLD and a future potential therapeutic target to treat NAFLD.

Serum-soluble CXCL16 in juvenile systemic lupus erythematosus: a promising predictor of disease severity and lupus nephritis.

Juvenile systemic lupus erythematosus (jSLE) is a multisystem autoimmune disease of unpredicted course and prognosis. Rates of organ involvement in SLE are higher in children, and overt lupus nephropathy is more often a presenting manifestation of SLE in children than adults. Inflammatory soluble chemokine CXC motif-ligand 16 (sCXCL16) is an important pathogenic mediator in inflammatory diseases as SLE. Herein, we aimed to evaluate serum level of sCXCL16 in jSLE patients in comparison to healthy controls and to correlate it with disease activity and extent of cutaneous and renal affection, to detect its possible role in disease pathogenesis. Serum level of sCXCL16 was determined by ELISA in 27 patients with jSLE (mean age 12.35 years ± 2.26 SD) in addition to 30 age- and sex-matched healthy controls and correlated with clinical and laboratory parameters in lupus group. Serum sCXCL16 was significantly higher in jSLE patients than controls (P ≤ 0.001), and it correlated positively with SLE disease activity, severity of lupus nephritis, 24-h urinary protein, anti-dsDNA titre, blood pressure, and ESR, while it correlated negatively with serum C3 levels. Serum sCXCL16 was higher in jSLE patients with alopecia and malar erythema. Serum sCXCL16 might play a role in inflammatory pathogenesis of jSLE particularly in periods of disease activity. It might serve as a future useful laboratory test for detection of jSLE activity, renal insult, and its severity which might limit the need for invasive renal biopsies in such a delicate patient population.

Chemokine CXCL16 mediates acinar cell necrosis in cerulein induced acute pancreatitis in mice.

Severe acute pancreatitis is a lethal inflammatory disease frequently accompanied by pancreatic necrosis. We aimed to identify a key regulator in the development of pancreatic necrosis. A cytokine/chemokine array using sera from patients with acute pancreatitis (AP) revealed that serum CXCL16 levels were elevated according to the severity of pancreatitis. In a mouse model of AP, Cxcl16 expression was induced in pancreatic acini in the late phase with the development of pancreatic necrosis. Cxcl16-/- mice revealed similar sensitivity as wild-type (WT) mice to the onset of pancreatitis, but better resisted development of acinar cell necrosis with attenuated neutrophil infiltration. A cytokine array and immunohistochemistry revealed lower expression of Ccl9, a neutrophil chemoattractant, in the pancreatic acini of Cxcl16-/- mice than WT mice. Ccl9 mRNA expression was induced by stimulation with Cxcl16 protein in pancreatic acinar cells in vitro, suggesting a Cxcl16/Ccl9 cascade. Neutralizing antibody against Cxcl16 ameliorated pancreatic injury in the mouse AP model with decreased Ccl9 expression and less neutrophil accumulation. In conclusion, Cxcl16 expressed in pancreatic acini contributes to the development of acinar cell necrosis through the induction of Ccl9 and subsequent neutrophil infiltration. CXCL16 could be a new therapeutic target in AP.

ADAM-17 is expressed in the inflammatory myopathy and is involved with interstitial lung disease.

The "A disintegrin and metalloprotease" (ADAM) family is thought to play an important role in tissue destruction and inflammatory reactions. ADAM-17 was first described as the protease responsible for tumor necrosis factor (TNF)-α shedding. Here, we have shown the expression of ADAM-17 in inflammatory myopathy and demonstrated the role of inflammation in interstitial lung diseases (ILD). ADAM-17 in inflammatory myopathy serum [polymyositis (n = 26), dermatomyositis (n = 34), and clinically amyopathic dermatomyositis (n = 10)] and healthy control (n = 19) was measured using enzyme-linked immunosorbent assay. The relationship between ADAM-17 and clinical data was examined. Finally, we performed immunohistological analysis to investigate the expression of ADAM-17 on the muscles of the inflammatory myopathy patients. ADAM-17 in inflammatory myopathy was significantly higher than that in healthy control (mean ± SEM, 1048 ± 312 and 36 ± 18 pg/ml, respectively; p < 0.05). ADAM-17 in post-treatment with corticosteroid and/or immunosuppressant serum was significantly decreased compared with that in pre-treatment serum (1465 ± 562 and 1059 ± 503 pg/ml, respectively; p < 0.01). ADAM-17 was significantly positively correlated with fractalkine/CX3CL1 and CXCL16. In addition, ADAM-17 in inflammatory myopathy with ILD patients (n = 46) was significantly higher than that in non-ILD patients (n = 24) (1379 ± 454 and 413 ± 226 pg/ml, respectively; p < 0.05). We found the expression of ADAM-17 on muscle biopsy tissue. ADAM-17 is expressed in inflammatory myopathies especially ILD, suggesting that ADAM-17 plays a role in lung fibrosis. ADAM-17 may be a potential target in inflammatory myopathies with ILD.

IFN-γ, CXCL16, uPAR: potential biomarkers for systemic lupus erythematosus.

OBJECTIVES: IFN-γ, CXCL16 and uPAR have recently been regarded as potential biomarkers in systemic lupus erythematosus (SLE). However, few researches have focused on the comparison of these three markers in SLE. We conducted this study to evaluate their role as biomarkers of disease activity and renal damage. METHODS: We enrolled 50 SLE patients with or without lupus nephritis (LN) and 15 healthy control subjects. The levels of IFN-γ, CXCL16, uPAR in serum, urine and renal tissues were detected by ELISA or immunohistochemistry. Relevant clinical and laboratory features were recorded. RESULTS: Serum and urine IFN-γ, CXCL16 and suPAR levels in SLE patients were significantly higher than that in healthy controls. Moreover, LN patients had higher levels than non-LN patients. A positive correlation was observed between these markers, and disease activity and suPAR had a stronger association with disease activity. The expression of these biomarkers in renal tissues was significantly higher in LN patients and was also associated with the activity of pathological lesions. CONCLUSIONS: IFN-γ, CXCL16 and uPAR are promising as effective biomarkers of disease activity, renal damage, and the activity of pathological lesions in SLE.

Biomarkers of cerebral microembolic signals.

Stroke is a major cause of mortality and morbidity around the world. Microembolic signals (MES), as the markers of unstable atherosclerotic plaque, can predict the occurrence and prognosis of ischemic stroke (IS). MES can also assess the efficacy of antithrombotic agents and predict the recurrence probability of IS. Unstable plaques are the main source of MES; thus, numerous biomarkers of atherosclerotic plaque instability are highly likely to predict the presence of MES. This study aims to review recent biomarker candidates for MES or microembolism. Current research indicates that the following are independent markers for positive MES: high level of serum soluble P-selectin, chemokine (C-X-C motif) ligand 16 (CXCL16) and fibrinogen, high neutrophil count, reduced ratio of CD4+CD25high regulatory T cells (Tregs) and the C allele of tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) rs3102735. However, a more integrated profile of biomarkers for MES is needed to improve the stratification of patients with carotid stenosis and enhance the effectiveness of therapeutic interventions and prevention for IS.

The relationship between serum CXCL16 level and carotid vulnerable plaque in patients with ischemic stroke.

OBJECTIVE: We investigated the relationship between the serum macrophage chemokine ligand 16 (CXCL16) levels and the vulnerable carotid plaque in patients with ischemic stroke. PATIENTS AND METHODS: We successively selected 118 cases of patients with an initial diagnosis of acute ischemic stroke (time of onset < 72 h), recorded risk factors, including gender, age, family history, smoking, body mass index, blood glucose levels, blood lipid levels, average systolic pressure and diastolic blood pressure (DBP) and homocysteine levels. ELISA was used to detect the levels of serum CXCL16. GE-3000 color Doppler ultrasound diagnostic instrument was applied for the detection of the cervical artery (including a bilateral common carotid artery, internal carotid artery and external carotid artery) intima-media thickness (IMT), plaque number, size, nature (stable and vulnerable) and luminal stenosis rate. Delica EMS-9EBx2P type transcranial Doppler ultrasound (TCD) was used to detect micro-arterial micro-embolic signals (MES). Stroke, according to etiologic type, was divided into large artery atherosclerosis (LAA), small artery occlusion (SAA) and others. RESULTS: Serum CXCL16 levels were not significantly correlated with sex, age, family history, smoking, BMI, blood glucose levels, blood lipid levels, mean systolic blood pressure, diastolic blood pressure, and homocysteine levels. Serum CXCL16 levels increased with an increase of IMT, plaque area and lumen stenosis rate. Serum CXCL16 levels of vulnerable plaques were significantly higher than those of stable plaques; differences were statistically significant (p<0.05). It has nothing to do with the number of atherosclerotic plaques. The levels of serum CXCL16 in MES positive group were significantly higher than that in MES negative group; differences were statistically significant (p<0.05). The serum CXCL16 levels of LAA patients were significantly higher than that of SAA and other types of patients; differences were statistically significant (p<0.05). CONCLUSIONS: The levels of serum CXCL16 are not related to high-risk factors for acute stroke and closely related to characteristics of atherosclerotic plaque, micro-embolic signals and stroke subtypes.

CXC chemokine ligand 16 is increased in gestational diabetes mellitus and preeclampsia and associated with lipoproteins in gestational diabetes mellitus at 5 years follow-up.

BACKGROUND: Women with a history of gestational diabetes mellitus and preeclampsia are at increased risk of cardiovascular disease later in life, but the mechanism remains unclear. The aim of the study was to evaluate the association between CXC chemokine ligand 16 and indices of glucose metabolism, dyslipidemia and systemic inflammation in gestational diabetes mellitus and preeclampsia. METHODS: This sub-study of the population-based prospective cohort included 310 women. Oral glucose tolerance test was performed during pregnancy and 5 years later along with lipid analysis. CXC chemokine ligand 16 was measured in plasma (protein) and peripheral blood mononuclear cells (messenger RNA) during pregnancy and at follow-up. RESULTS: Circulating CXC chemokine ligand 16 was higher in gestational diabetes mellitus women early in pregnancy and at follow-up, while higher in preeclampsia women late in pregnancy compared to control women. Messenger RNA of CXC chemokine ligand 16 in peripheral blood mononuclear cells were lower in gestational diabetes mellitus and preeclampsia women compared to control women. Increased circulating CXC chemokine ligand 16 level was associated with a higher apolipoprotein B and low-density lipoprotein cholesterol in gestational diabetes mellitus women but not in normal pregnancy at follow-up. CONCLUSION: Our study shows that women with gestational diabetes mellitus and preeclampsia had a dysregulated CXC chemokine ligand 16 during pregnancy, and in gestational diabetes mellitus, the increase in CXC chemokine ligand 16 early in pregnancy and after 5 years was strongly associated with their lipid profile.