sCD40L Levels Research Articles

High Serum sCD40L Levels During the First Week of Malignant Middle Cerebral Artery Infarction and Mortality

Higher circulating soluble cluster of differentiation 40 ligand (sCD40L) levels at admission of an ischemic stroke have been found in nonsurvivor than in survivor patients. The objectives of this study were to determine whether serum sCD40L levels during the first week of a severe malignant middle cerebral artery infarction (MMCAI) are higher in nonsurvivor than in survivor patients and whether they could be used as biomarker of mortality prediction. This multicenter study included patients with severe MMCAI (defined as Glasgow Coma Scale score <9). We determined serum sCD40L concentrations at days 1, 4, and 8 and performed receiver operating characteristic analyses to determine their capacity for 30-day mortality prediction. Nonsurvivors (n= 34) showed higher sCD40L levels on days 1 (P < 0.001), 4 (P= 0.004), and 8 (P < 0.001) than did survivor patients (n= 34). Areas under the curve of serum sCD40L concentrations at days 1, 4, and 8 of severe MMCAI for 30-day mortality prediction were 83% (P<0.001), 89% (P < 0.001), and 87% (P < 0.001), respectively. The findings that nonsurvivors showed higher serum sCD40L levels during the first week of MMCAI than did survivors and that serum sCD40L levels during the first week of MMCAI could be used as a mortality predictor biomarker are 2 novel findings.

Assessment of CD40 and CD40L expression in rheumatoid arthritis patients, association with clinical features and DAS28.

The predominance of the effector mechanisms by CD4 + T cells is a characteristic of inflammatory autoimmune diseases such as rheumatoid arthritis (RA). The CD40/CD40L costimulatory pathway contributes to these pathogenic mechanisms by promoting autoantibody production and inflammation. Aberrant expression of CD40 and CD40L in RA patients has been shown, the latter prevailing in females. However, contrasting results have emerged regarding the clinical associations of these findings. We determined the association of CD40 and CD40L expression with the clinical activity evaluated through DAS28 in RA patients. A total of 38 female RA patients and 10 age- and sex-matched control subjects were included. CD40 and CD40L mRNA expression was quantified by real-time qPCR, cell surface proteins were determined by flow cytometry, and protein soluble forms were determined by ELISA. The expansion of a CD4 + T cell subpopulation expressing CD40 was identified in the RA group. In addition, high frequencies of CD4 + CD40L + T cells expressing high levels of CD40L, increased levels of sCD40L and overexpression of CD40L mRNA were observed in these patients. Moreover, there was a gradual increase in CD40L when data were stratified according to DAS28, except for very active patients. No correlation was observed between the levels of mRNA, cell surface protein and soluble protein of CD40 and CD40L with the clinical features of RA patients. There is an altered expression of CD40L in female RA patients in association with clinical activity assessed by DAS28, these findings support the evidence that suggests CD40L as a marker of clinical activity.

Association between the No-Reflow Phenomenon and Soluble CD40 Ligand Level in Patients with Acute ST-Segment Elevation Myocardial Infarction.

Background and objectives: No-reflow (NR) phenomenon is defined as insufficient myocardial perfusion in coronary circulation in the absence of angiographic evidence of mechanical obstruction. The primary mechanisms of the NR occurrence are thought to be high platelet activity and thrombus burden. Soluble CD40 ligand (sCD40L), which is released into the plasma following platelet activation, accelerates the inflammatory process and causes further platelet activation. The aim of our study is to investigate the relationship between the NR phenomenon and sCD40L level in patients with ST-elevation myocardial infarction (STEMI). Methods: A total of 81 acute STEMI patients undergoing primary percutaneous coronary intervention and 40 healthy participants were included in this study. Acute STEMI patients were classified into two groups: 41 patients with the NR phenomenon (NR group) and 40 patients without the NR phenomenon (non-NR group). The serum sCD40L level was measured for all groups. Results: The serum sCD40L level was significantly higher in the NR group than in non-NR and control groups (379 ± 20 pg/mL, 200 ± 15 pg/mL and 108 ± 6.53 pg/mL, respectively; p < 0.001). Univariate regression analysis demonstrated that male sex, age, Gensini score and sCD40L level were the possible factors affecting the occurrence of the NR phenomenon. In multivariate regression analysis, age (odds ratio [OR], 1.091; 95% confidence interval [CI], 1.023–1.163; p < 0.008) and serum sCD40L (OR, 1.016; 95% CI, 1.008–1.024; p < 0.001) remained the independent predictor of the presence of NR. Conclusions: Our study showed that serum sCD40L level was an independent predictor of the NR phenomenon occurrence.

Abstract 416: Predictive significance of serum protein levels in advanced non-small-cell lung cancer patients treated with pembrolizumab

Abstract Background: We have previously reported that serum IL-8 and G-CSF were correlated with clinical benefit and immune-related adverse events (irAE), respectively in non-small-cell lung cancer (NSCLC) patients treated with nivolumab. Here, we measured multiple serum proteins serially in NSCLC patients treated with pembrolizumab and explored the potential of predicting clinical response or irAE onset. This study was registered at UMIN (ID: 000024414). Patients and Methods: Advanced NSCLC patients received pembrolizumab monotherapy (200 mg/body, q3W) until progressive disease (PD) or unacceptable toxicity. Serum samples were collected at baseline and at week 6. Best response was classified into partial response (PR), stable disease (SD), or progressive disease (PD) according to RECIST v1.1. Using LuminexTM xMapTM technology, serum levels of 41 proteins consisting of cytokines, chemokines, growth factors, and angiogenesis factors were measured. All statistical analyses were carried out using JMP Pro software (ver. 13.0) and Mann-Whitney U test were performed accordingly. A p value &amp;lt;0.05 was considered as significant. Results: Thirty-seven patients were registered in the study between March 2017 and October 2018 at Wakayama Medical University Hospital and 32 were included in the final analysis. Demographics of the patients were as follows: median age 70 (range, 50 to 91); male 75%; smoker 88%; stage III/IV, 22/78%; squamous/non-squamous, 31/69%, previous treatment; 0/1≤, 47/53%. Objective response rate was 28% and disease control rate was 56% in the entire cohort and 40% and 67%, respectively in the first-line subset. Among 41 serum proteins measured, no serum protein at baseline was associated with efficacy or irAE onset in the entire cohort. Levels of serum VEGF-C and sCD40L at baseline, however, in the first-line subset were found significantly lower in the patient who had PR and SD than those who did not. RANTES was also found significantly lower in patients who had PR in the 2nd or later line subset. With regard to irAE prediction, changes of HB-EGF levels between baseline and week 6 were significantly smaller in irAE patients in the entire cohort and changes of MCP-1 levels were significantly smaller in irAE patients in second or later line subset. The serum proteins identified in the current study were not overlapped with those identified in advanced NSCLC patients treated with nivolumab in the previous study. Conclusions: We identified potential serum protein markers associated with clinical benefit and irAE from pembrolizumab treatment in advanced NSCLC by multi-analyte protein-based assay. Our results suggest that serum proteins associated with efficacy and irAE may vary among different anti-PD-1 antibodies and also between in the first-line setting and later one. Citation Format: Jun Oyanagi, Yasuhiro Koh, Shunsuke Teraoka, Kuninobu Kanai, Atsuhsi Hayata, Nahomi Tokudome, Hiroaki Akamatsu, Yuichi Ozawa, Keiichiro Akamatsu, Masanori Nakanishi, Hiroki Ueda, Nobuyuki Yamamoto. Predictive significance of serum protein levels in advanced non-small-cell lung cancer patients treated with pembrolizumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 416.

Analysis of Genetic Variation in CD40 and CD40L: Relationship with mRNA Relative Expression and Soluble Proteins in Acute Coronary Syndrome.

Acute coronary syndrome (ACS) can be triggered by the presence of inflammatory factors which promote the activation of immune cells by costimulatory molecules such as CD40 and its ligand CD40L. Environmental and genetic factors are involved in the etiology of the ACS. The aim of this study was to explore the gene and protein expression associated with CD40 and CD40L genetic variants in ACS patients from the western Mexican population. A total of 620 individuals from western Mexico were recruited: 320 ACS patients and 300 individuals without a history of ischemic cardiopathy were evaluated. The genotype was determined using TaqMan SNP genotyping assays. CD40 and CD40L expressions at the mRNA level were quantified using TaqMan Gene Expression Assays. Soluble protein isoforms were measured by enzyme-linked immunosorbent assay. We did not find evidence of association between CD40 (rs1883832, rs4810485, and rs11086998) and CD40L (rs3092952 and rs3092920) genetic variants and susceptibility to ACS, although rs1883832 and rs4810485 were significantly associated with high sCD40 plasma levels. Plasma levels of sCD40L can be affected by gender and the clinical spectrum of acute coronary syndrome. Our results do not suggest a functional role of CD40 and CD40L genetic variants in ACS. However, they could reflect the inflammatory process and platelet activation in ACS patients, even when they are under pharmacological therapy. Due to the important roles of the CD40-CD40L system in the pathogenesis of ACS, longitudinal studies are required to determine if soluble levels of CD40 and CD40L could be clinically useful markers of a recurrent cardiovascular event after an ACS.

Preoperative Platelet Activation Markers as a Risk Predictor of Postoperative Atrial Fibrillation after Coronary Artery Bypass Grafting

Background: Atrial fibrillation (AF) is the most well-known arrhythmia following coronary artery bypass grafting (CABG) that in turn may lead to a longer hospital stay and a worse postoperative prognoses. AF is known to be a cause of platelet activation; we investigated the relationship between the platelet activation markers and the risk of AF after coronary bypass graft surgery. Methods: Blood was drawn one day before the operation from fifty patients scheduled for isolated on pump CABG. The monocyte–platelet aggregates (MPAs) content were assessed by Flow cytometric quantification analysis. Moreover, soluble CD40 Ligand (sCD40L) level, soluble P-selectin (sP-selectin) and D-dimer levels were quantified by immunological ELISA technique. Post-operative AF (POAF) events were followed up during hospitalization. Results: Post-operative AF (POAF) noticed in 22% of patients, in the first postoperative week. Preoperative levels of both sCD40L, sP-selectin and D-Dimer were significantly higher in those who developed POAF. CD41 expression on monocytescellular marker of platelet activation- and the content of MPAs were increased in those patients encountered POAF. Conclusion: Preoperative platelet activation as affirmed by both soluble and cellular markers in addition to the content of MPAs markers seems to be an unprecedented predictor of the postoperative atrial fibrillation.

Nonsurviving Patients with Severe Traumatic Brain Injury Have Maintained High Serum sCD40L Levels

Soluble cluster of differentiation 40 ligand (sCD40L) is a member of the tumor necrosis factor family with proinflamatory and procoagulant effects. A previous study found higher serum sCD40L levels at day 1 of traumatic brain injury (TBI) in nonsurviving than surviving patients. Thus the objective of this study was to compare serum sCD40L levels during the first week of a severe TBI between surviving and nonsurviving patients and to determine whether it could be used as a mortality predictor biomarker. In this multicenter study severe TBI patients (with Glasgow Coma Scale score <9) with an Injury Severity Score in noncranial item <9 were included. Serum sCD40L concentrations at days 1, 4, and 8 of TBI were determined. We performed receiver operating characteristic analyses to determine the capacity of 30-day TBI mortality prediction by serum sCD40L levels at days 1, 4, and 8 of TBI. We found that nonsurviving (n= 34) patients in comparison with surviving (n= 90) patients had higher sCD40L levels on days 1 (P < 0.001), 4 (P= 0.004), and 8 (P<0.001) of TBI. We also found that the areas under curve of serum sCD40L concentrations at days 1, 4, and 8 of TBI to 30-day mortality prediction were 82% (P < 0.001), 72% (P=0.01) and 83% (P < 0.001), respectively. The existence of higher serum sCD40L levels in nonsurviving than surviving patients during the first week of TBI and fact that serum sCD40L levels during the first week of TBI can be used as a mortality predictor biomarker are the new findings of our study.

Transferrin Saturation Inversely Correlates with Platelet Function.

The association between iron overload (IO) and risk of cardiovascular disease is controversial. Epidemiological studies have found a significant negative association of transferrin (Tf) saturation and cardiovascular events suggesting that higher body iron possibly confer a protective effect towards developing cardiovascular events. The biological mechanisms of this phenomenon are unknown. This article investigates the role of IO on platelet reactivity. This study was a prospective case-control study comparing 45 patients with IO, mostly characterized by the HFE gene mutations C282Y and/or H63D, with 32 healthy controls. We evaluated: (1) platelet aggregation in both platelet-rich plasma and whole blood, (2) platelet membrane expression of the activation marker CD62P, (3) activation of platelet signalling phosphoinositide 3-kinase /Akt and mitogen-activated protein kinase/extracellular signal-regulated kinases (Erk)-1/2 pathways, (4) a pattern of in vivo platelet activation markers, and (5) iron biomarker predictors of platelet reactivity. IO patients had significantly lower platelet aggregability, expression of CD62P and phosphorylation amounts of pAkt and pErk-2 in response to agonists. Furthermore, patients with higher Tf saturation levels were characterized by lower circulating levels of sCD40L, PDGF-BB and thromboxane B2. Platelet aggregation and activation parameters inversely correlated with Tf saturation and the stepwise multivariate regression analysis underlined the role of Tf saturation in predicting platelet reactivity. We also found that in vitro platelet exposure to diferric Tf, but not to iron-depleted TF, dose-dependently inhibited platelet function in all investigated subjects. Tf saturation is inversely associated with platelet reactivity and this could explain, at least in part, the association of high Tf and lower risk of cardiovascular diseases in IO.

The skewed frequency of B-cell subpopulation CD19+ CD24 hi CD38 hi cells in peripheral blood mononuclear cells is correlated with the elevated serum sCD40L in patients with active systemic lupus erythematosus.

CD19+ CD24hi CD38hi cells play an essential role in maintaining immune homeostasis. CD40 signaling is involved in regulating the induction and function of CD19+ CD24hi CD38hi cells. Changes in B-cell subpopulations and CD19+ CD24hi CD38hi cells have been observed in systemic lupus erythematosus (SLE) patients. Whether changes in the B-cell subpopulation are related to the aberrant CD40 signaling in SLE patients remains unclear. In this study, we examined changes in the levels of CD19+ CD24hi CD38hi cells and CD19+ CD24hi CD38low cells in peripheral blood mononuclear cells and the serum level of soluble CD40 ligand (sCD40L) in 30 patients with SLE. Through routine biochemical assays and flow cytometry assay, we found that (1) the CD19+ CD24hi CD38hi cell subset was upregulated in SLE patients compared to that in healthy controls (HCs) (P < 0.05); (2) the CD19+ CD24hi CD38low cell subset was downregulated in SLE patients compared with that in HCs; and (3) CD38 expression was positively correlated with SLE manifestations and the serum sCD40L level (P < 0.05). In conclusion, the relative level of Bregs is significantly higher in SLE patients than in HCs and is positively correlated with disease activity and sCD40L level.

Evaluation of plasma levels of neopterin and soluble CD40 ligand in patients with acute ischemic stroke in upper Egypt: can they surrogate the severity and functional outcome?

Inflammation constitutes a major component of ischemic stroke pathology. The prognostic value of "neopterin" and soluble CD40 ligand (sCD40L), as a potential biomarker of ischemic stroke, has been less extensively studied. This study aims at assessing the serum levels of neopterin and sCD40L in acute ischemic stroke (AIS), to clarify its association with the severity, etiology, and risk factors of stroke, and to evaluate their relationship with the stroke functional outcome in our study sample within 90 days of follow-up. This case-control study was conducted on 100 patients with first-ever acute onset ischemic stroke and 25 control subjects. Participants were subjected to full history taking and detailed clinical and neurological examination. Brain imaging was performed after hospital admission. Blood tests were drawn for assessment of neopterin and sCD40L on the first day of admission. High levels of neopterin and sCD40L was reported. Their levels were significantly higher in relation with survival status. There was a relationship between AIS and sCD40L levels and the severity of the stroke. Within 3 months of follow-up, these biomarkers were associated significantly with poor functional outcome, within a 90-day follow-up period, and mortality. These biomarkers were highly associated in patients with small vessel occlusion as an etiology for AIS. Neopterin and sCD40L levels increased after AIS. Both biomarkers were strong and independent predictors of 90-day unfavorable clinical outcome and death in patients after AIS.

Serum Levels of Soluble CD40 Ligand and Neopterin in HIV Coinfected Asymptomatic and Symptomatic Visceral Leishmaniasis Patients.

Human Immunodeficiency Virus (HIV) co-infection drastically increases the risk of developing overt visceral leishmaniasis (VL). The asymptomatic Leishmania infection window constitutes an opportunity to identify those HIV patients at highest risk by defining early markers associated with disease susceptibility or resistance. As intracellular parasite killing is essential, we investigated whether serum markers of macrophage activation were notably affected in HIV patients with an asymptomatic Leishmania infection or overt visceral leishmaniasis disease. Serum levels of soluble CD40 ligand and neopterin were assessed in 24 active VL-HIV patients, 35 HIV patients with asymptomatic Leishmania infection and 35 HIV endemic controls. All patients were recruited in L. donovani endemic regions of North-West Ethiopia. The serum levels of sCD40L and neopterin significantly decreased and increased in HIV patients with active VL compared to HIV patients with asymptomatic Leishmania infection, respectively. No statistically significant differences could be detected in neopterin and sCD40L levels between Leishmania asymptomatically infected HIV patients and endemic HIV control patients. However, an inverse trend, between Leishmania antibody positivity or VL development and neopterin levels could be seen. The CD4+ T-cell count was inversely correlated with serum neopterin levels, but not with sCD40L levels. Our results in HIV coinfected patients, correspond with the postulated protective role of sCD40L in VL and underline the importance of the CD40-CD40L pathway in resistance against the parasite. Neopterin levels suggest an increased macrophage activation upon infection and could have a value in clinical algorithms to, although non-specifically, improve prediction of VL development in HIV patients with asymptomatic Leishmania infection.

Cytokine profiles in cerebrospinal fluid of patients with meningitis at a tertiary general hospital in China.

There has been a great deal of evidence indicating that cytokines participate in meningeal inflammation. Different cytokine profiles may be presented in central nervous system (CNS) infection due to different pathogens. We have attempted to investigate cytokine profiles in cerebrospinal fluid (CSF) of patients with CNS infection. Forty-three patients with CNS infection including tuberculous meningitis, purulent meningitis and cryptococcal meningitis were enrolled and 11 patients with normal CSF were enrolled as control group. The concentrations of Th1-, Th2- and Th17-type cytokines in CSF were detected using multiplex cytokine assay. Furthermore, the correlation between CSF cytokines and CSF parameters in CNS infection was analyzed. The CSF levels of IL-1β, IL-4, IL-6, IL-10, IL-17, IL-23, IL-33, IFN-γ, TNF-α and sCD40L among the patients with CNS infection were all higher than control group (all P<0.05). A remarkable elevation of CSF IL-6 in the patients with CNS infection was observed with the least overlap of the CSF concentrations compared to controls. Moreover, CSF IL-6 levels were strongly negatively correlated with CSF glucose and the CSF/blood glucose ratio (r=-0.4375, P=0.0042; r=-0.4991, P=0.0009). The excessive activation of immune response characterized by elevated levels of CSF Th1-, Th2- and Th17-type cytokines has been observed during CNS infection. Furthermore, we observed negative correlations between CSF IL-6 levels and CSF glucose and CSF/blood glucose ratio in CNS infection. And we suggested that combined CSF IL-6 levels with CSF glucose may serve as a novel biomarker pool for the differential of CNS infection.

Short- and long-term effects of hemodialysis on platelet and monocyte activity markers of atherosclerosis in patients with end-stage renal disease.

In hemodialysis (HD) patients cardiovascular events represent the predominant cause of mortality. Since platelet and monocyte activity markers play an important role in cardiovascular mortality, this study assessed the influence of HD on these markers. Forty one HD patients (25 male, 16 female) were included. Blood samples were obtained before and after a single HD session at baseline and again after an elapsed period of 114 ± 21 days (91-175 days) on maintenance hemodialysis. Surface expression of CD40L and CD62P on platelets, tissue factor binding on monocytes and platelet-monocyte aggregates were measured by flow cytometry. Plasma levels of monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFa) and soluble CD40L were analyzed by enzyme linked immunosorbent assay. Tissue factor on monocytes was significantly increased after a single HD session at baseline (p = 0.041), whereas platelet-monocyte aggregates, the expression of CD40L and CD62P on platelets did not change significantly. After a mean of 114 ± 21 days of HD therapy, tissue factor on monocytes (p < 0.0001), platelet-monocytes aggregates (p < 0.0001), plasma levels of MCP-1 (p = 0.012) and TNFa (p = 0.046) were significantly decreased compared to baseline values. In contrast, platelet surface expression of CD40L and CD62P as well as plasma levels of sCD40L and IL-6 were not attenuated significantly. There was no significant correlation detected between the markers examined and the cumulative time on hemodialysis. Platelet and monocyte activity markers assessed in this study do not appear to be significantly increased by HD therapy. Therefore, these markers probably cannot be accountable for increased cardiovascular mortality in chronic HD patients.

Elevation in Circulating Soluble CD40 Ligand Concentrations in Type 2 Diabetic Retinopathy and Association with its Severity.

To investigate the relationship between changes in circulating soluble CD40 ligand (sCD40L) levels and the presence and severity of type 2 diabetic retinopathy (DR). sCD40L plasma concentrations were measured in 205 type 2 diabetes (T2DM) patients without DR (DWR; n=50) and with DR (n=155), the latter subdivided into non-proliferative diabetic retinopathy [NPDR; n=98 (63.2%)], or proliferative retinopathy [PDR; n=57 (36.8%)] patients. Receiver operating characteristic analysis provided good discriminatory power for sCD40L as predictor of DR presence, with high sensitivity and specificity. Categorizing DWR and DR patients into sCD40L quartiles, based on sCD40L concentrations in T2DM without DR, demonstrated statistically significant gradual increase in DR risk with increasing sCD40L levels. sCD40L levels were significantly higher in DR compared to DWR patients. Plasma sCD40L levels differed significantly according to DR severity, and correlated with diabetes duration, dyslipedimea, nephropathy, and presence of DR, but not with gender, age, SBP, DBP, FPG, HbA1c, T2DM medications. Linear regression analysis confirmed the association of increased sCD40L levels with DR, independent of others parameters; mean plasma sCD40L levels differing significantly according to DR severity. Plasma sCD40L levels were positively associated with DR. The significant finding here is that sCD40L levels can be predictors of DR severity.

Correlation of sCD40L Level with Force Vital Capacity Value in Restrictive Lung Disease of Systemic Sclerosis Patients

Background: Interstitial Lung Disease (ILD) is one of the major cause of morbidity and mortality in Systemic Sclerosis (SSc). The gold standard to diagnose ILD is using High Resolution Computed Tomography (HRCT) scan. HRCT scan need a lot of cost and not always available, so another diagnosing test is needed as an alternative modality to diagnose ILD. ILD is a restrictive lung disease caused by lung fibrosis which is proved by the decrease of Forced Vital Capacity (FVC) in spirometry, and followed by the increase of soluble CD40L (sCD40L) level in plasma. This sCD40L may become a potential biomarker to evaluate lung fibrosis in SSc patients. The aim of this study is to analyze the correlation of sCD40L levels with FVC score in SSc patients with restrictive lung disease.Method:This cross sectional study was enrolled by the SSc patient who has restrictive lung disease based on spirometry test, at Rheumatology outpatient clinic dr. Hasan Sadikin Hospital from May 2015 to May 2016. All subject took underwent history, physical examination, spirometry and blood test for sCD40L. Data were analyzed using Pearson correlation.Result:There were 38 subjects involved in this study, dominated bywoman (92.1%) with mean age 41(±11) years. Subjects consist of 22(57,9%) with limited SSc, 16(42,1%) with diffuse SSc patients and 33 subjects treated with DMARD. Mean sCD40L serum in this study was 6.690,3(±2.377,3) pg/mL, with no statistical difference between limited and diffuse type (p=0.154). Mean FVC score in this study was 58.2(±10,8). There was no significant correlation between sCD40L serum with FVC (r=0.058; p=0.366). There was weak correlation on DMARD naïve subject between sCD40L serum and FVC (r=0.058; p=0.366) but statistically insignificant. There was no significant correlation between sCD40L serum with mRSS (r=0,066; p=0,346).Conclusion: This study founds no correlation between sCD40L with FVC in SSc at dr. Hasan Sadikin Hospital. Keyword : sCD40L, Forced Vital Capacity, Restrictive Lung Disease, Systemic Sclerosis

Correlation of sCD40L Level with Force Vital Capacity Value in Restrictive Lung Disease of Systemic Sclerosis Patients

Background: Interstitial Lung Disease (ILD) is one of the major cause of morbidity and mortality in Systemic Sclerosis (SSc). The gold standard to diagnose ILD is using High Resolution Computed Tomography (HRCT) scan. HRCT scan need a lot of cost and not always available, so another diagnosing test is needed as an alternative modality to diagnose ILD. ILD is a restrictive lung disease caused by lung fibrosis which is proved by the decrease of Forced Vital Capacity (FVC) in spirometry, and followed by the increase of soluble CD40L (sCD40L) level in plasma. This sCD40L may become a potential biomarker to evaluate lung fibrosis in SSc patients. The aim of this study is to analyze the correlation of sCD40L levels with FVC score in SSc patients with restrictive lung disease.Method:This cross sectional study was enrolled by the SSc patient who has restrictive lung disease based on spirometry test, at Rheumatology outpatient clinic dr. Hasan Sadikin Hospital from May 2015 to May 2016. All subject took underwent history, physical examination, spirometry and blood test for sCD40L. Data were analyzed using Pearson correlation.Result:There were 38 subjects involved in this study, dominated bywoman (92.1%) with mean age 41(±11) years. Subjects consist of 22(57,9%) with limited SSc, 16(42,1%) with diffuse SSc patients and 33 subjects treated with DMARD. Mean sCD40L serum in this study was 6.690,3(±2.377,3) pg/mL, with no statistical difference between limited and diffuse type (p=0.154). Mean FVC score in this study was 58.2(±10,8). There was no significant correlation between sCD40L serum with FVC (r=0.058; p=0.366). There was weak correlation on DMARD naïve subject between sCD40L serum and FVC (r=0.058; p=0.366) but statistically insignificant. There was no significant correlation between sCD40L serum with mRSS (r=0,066; p=0,346).Conclusion: This study founds no correlation between sCD40L with FVC in SSc at dr. Hasan Sadikin Hospital. Keyword : sCD40L, Forced Vital Capacity, Restrictive Lung Disease, Systemic Sclerosis

Impact of Tobacco Versus Electronic Cigarette Smoking on Platelet Function

Electronic cigarettes (E-cigarettes) have become popular as substitutes for conventional tobacco cigarettes or to aid quitting, but little is known about the potential risks to cardiovascular health for smokers and nonsmokers. We sought to compare the impact of E-cigarettes with conventional cigarettes on platelet function in healthy adult smokers and nonsmokers. A crossover single-blind study in 40 healthy participants (20 smokers, 20 nonsmokers, matched for age and sex) was conducted. Each participant smoked a conventional cigarette then returned 1 week later to vape a study E-cigarette with the same nominal nicotine content. Blood samples were drawn shortly before and 5 minutes after each episode and analyzed for platelet aggregation, soluble CD40-ligand (sCD40L) and soluble P-selectin (sP-selectin). At baseline, smokers had significantly higher levels of sCD40L and sP-selectin (all p ≤0.01) than nonsmokers. Within 5 minutes of using either a conventional cigarette or E-cigarette, changes in the levels of sCD40L, sP-selectin, and platelet aggregation (all p ≤0.01) were detectable in both smokers and nonsmokers. In smokers, there were no significant changes in sCD40L and sP-selectin but there was a significant increase in platelet aggregation. In nonsmokers, there was a significant increase in all markers of platelet activation following both cigarette and E-cigarette use. Both traditional and E-cigarettes have short-term effects on platelet activation, although in nonsmokers the use of E-cigarettes had a less important impact. In conclusion, we provide the first comparison data of the acute impact of Tobacco-cigarette and E-cigarette smoking on the platelet function in smokers and nonsmokers.

Interplay between Oxidative Stress and Platelet Activation in Coronary Thrombus of STEMI Patients.

Background: Platelet activation and oxidative stress seem to play a key role in coronary thrombus formation and are associated with thrombus burden in ST-elevation myocardial infarction (STEMI). However, the interplay between oxidative stress and platelet activation has not been fully elucidated. Materials and Methods: For 32 patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) and 10 patients with stable angina (SA) and oxidative stress, as assessed by NADPH isoform 2 activity (soluble Nox2-derived peptide, sNox2-dp), levels of oxidized low-density lipoproteins (oxLDLs) and platelet activation markers such as soluble CD40 Ligand (sCD40L) and soluble P-selectin (sP-selectin) were measured in the retrieved material (coronary thrombi plus blood waste) of STEMI patients and in intracoronary blood of SA patients, respectively, and in peripheral blood samples of both groups. Results: In aspirated thrombi and blood waste of STEMI patients we found higher serum levels of sNox2-dp, oxLDLs, sCD40L, and sP-selectin, as compared to the intracoronary blood samples of SA patients. Moreover, in thrombi and blood waste of STEMI patients, a direct correlation between markers of oxidative stress and of platelet activation was found. Also, in STEMI patients a progressive increase of oxidative stress and platelet activation markers was observed according to the thrombus score burden. STEMI patients showed higher peripheral blood Nox2 activity and oxLDL levels as compared to SA patients. Conclusion: This study shows a close relationship between oxidative stress and platelet activation in the intracoronary blood waste and aspirated thrombi of STEMI patients, suggesting a role of oxidative stress in promoting thrombus formation and growth.

The CD40/CD40L system regulates rat cerebral microvasculature after focal ischemia/reperfusion via the mTOR/S6K signaling pathway

ABSTRACTObjective: The role of CD40/CD40 ligand (CD40L) in microvascular thrombosis is now widely accepted. However, the exact mechanisms linking the CD40/CD40L system and the soluble form of CD40L (sCD40L) with microvascular thrombosis are currently a topic of intensive research. The objective of this study was to assess the potential mechanisms in CD40/CD40L system-regulated microvascular thrombosis after focal ischemia/reperfusion (I/R).Methods: Rats were subjected to 60-min transient middle cerebral artery occlusion (MCAO). The experiments were divided into three groups: sham operation, MCAO, and MCAO + CD40 antagonist. Dynamic changes of serum-free sCD40L levels for 0, 1, 3, 5, 6, and 12 h by ELISA detecting kit after focal I/R were observed, and the CD40 expression levels in both platelet surface and vascular endothelial cell surface were measured by flow cytometry and immunofluorescence, respectively. Cerebral infarct volume was analyzed 12 h after reperfusion. mTOR/S6K signaling was determined by Western blot.Results: A comparison of thrombus formation between MCAO and CD40 antagonist treatment rats revealed a role for CD40 and/or CD40L in the inflammation-enhanced thrombosis responses in both of the platelet and vascular endothelial cell. MCAO rats yielded an acceleration of thrombus formation that was accompanied by increased CD40 levels in serum. The brain infarction was significantly decreased in CD40 antagonist treatment group compared to MCAO model group. The mTOR/S6K signaling was activated in MACO model than that of CD40 antagonist treatment group.Conclusions: Our findings indicate that CD40/CD40L system contributes to microvascular thrombosis and brain infarction induced by MCAO and reperfusion. The mTOR/S6K signaling pathway is involved in the regulation of cerebral microvasculature after focal I/R by CD40/CD40L.Abbreviations:AKT: protein kinase B; CD40L: CD40 ligand; CSF: cerebrospinal fluid; FITC: fluorescein isothiocyanate; I/R: ischemia/reperfusion; MCAO: middle cerebral artery occlusion; mTOR: mechanistic target of rapamycin; PE: P-phycoerythrin; sCD40L: soluble form of CD40L; TNF-a: tumor necrosis factor-alpha; WT: wild type.

Increase In Il-31 Serum Levels Is Associated With Reduced Structural Damage In Early Axial Spondyloarthritis

In spondyloarthritis, little is known about the relation between circulating cytokines and patient phenotype. We have quantified serum levels of T helper type 1 cell (Th1), Th2 and Th17 cytokines in patients with recent-onset axial spondyloarthritis (AxSpA) from the DESIR cohort, a prospective, multicenter French cohort consisting of 708 patients with recent-onset inflammatory back pain (duration >3 months but <3 years) suggestive of AxSpA. Serum levels of Th1, Th2, and Th17 cytokines were assessed at baseline in patients from the DESIR cohort fulfilling the ASAS criteria (ASAS+) and were compared with age- and sex-matched healthy controls. At baseline, ASAS+ patients (n = 443) and healthy controls (n = 79) did not differ in levels of most of the Th1, Th2 and Th17 cytokines except for IL-31, and sCD40L, which were significantly higher for ASAS+ patients than controls (p < 0.001 and p = 0.012, respectively). On multivariable analysis of ASAS+ patients, IL-31 level was associated with sCD40L level (p < 0.0001), modified Stoke AS Spine Score (mSASSS) < 1 (p = 0.035). The multivariable analyses showed that IL-31 was an independent factor associated with mSASSS < 1 (p = 0.001) and low bone mineral density (p = 0.01). Increased level of IL-31 might protect against structural damage but is also related to low BMD.