AB0844 SERUM sCD40L LEVEL CAN PREDICT SHORT-TERM CLINICAL OUTCOMES IN PATIENTS WITH PSORIATIC ARTHRITIS ON TREATMENT WITH APREMILAST.

Background:The pathogenesis of Psoriatic Arthritis (PsA) involves several pathways simultaneously, including the CD40/CD40L interaction. In vitro evidence suggests that the cleavage of soluble CD40L (sCD40L) may happen as a Phosphodiesterase 4- (PDE4) dependent reaction [1-3].Objectives:Here we investigate whether apremilast, a PDE4 inhibitor, could modify circulating level of soluble CD40L (sCD40L) in PsA patients, and the possible associations of these changes with clinical response.Methods:Consecutive patients with PsA starting apremilast in routine clinical practice between October 2018 and September 2019 in a single center were longitudinally observed. Sera were collected at baseline and at the 6-month follow up visit. Demographics and clinical characterstics at different observation times were recorded. Samples were ran in a Bio-Plex ProTM plate for sCD40L level. To investigate the association of sCD40L level with DAPSA minor response and DAPSA Low Disease Activity (LDA) and/or Remission (ie DAPSA ≤14) at 6 months of treatment, multivariate logistic regression models with backward selection (p <0.05) were built.Results:We studied n.27 patients (16/27 women, 59.6%) with PsA with mean age (± SD) of 58.4 ± 10.4 years. A significant reduction of the mean values of DAPSA, LEI and PASI was evidenced at 6 months. Mean serum level of sCD40L decreased from 5364.02 ± 2025.70 to 4412.14 ± 2629.81 pg/ml after 6 months of apremilast treatment (p=0.01, Figure 1). Baseline sCD40L was an independent predictor of DAPSA minor response (OR 1.0006, 95% CI 1.0001-1.0012; AUC 0.76 (95% CI 0.55-0.97)). Moreover baseline DAPSA (OR 0.80, 95% CI 0.65-0.98) and baseline sCD40L (OR 1.001, 95%CI 1.0001-1.0028; AUC 0.85 95% CI 0.69-0.98, Figure 2) were independently associated with DAPSA LDA/Remission.Conclusion:Apremilast may decrease sCD40L level in PsA patients. Higher baseline serum sCD40L level may predict short-term clinical response to apremilast.References:[1]Davidson DC, Jackson JW, Maggirwar SB. Targeting platelet-derived soluble CD40 ligand: a new treatment strategy for HIV-associated neuroinflammation? J Neuroinflammation 2013;10:144.[2]Vanichakarn P, Blair P, Wu C, Freedman JE, Chakrabarti S. Neutrophil CD40 enhances platelet-mediated inflammation. Thromb Res 2008;122(3):346-58.[3]Totani L, Amore C, Di Santo A, et al. Roflumilast inhibits leukocyte-platelet interactions and prevents the prothrombotic functions of polymorphonuclear leukocytes and monocytes. J Thromb Haemost 2016;14(1):191-204.Disclosure of Interests:Vincenzo Venerito: None declared, Dorotea Natuzzi: None declared, Rita Bizzoca: None declared, Nunzia Lacarpia: None declared, Marco Fornaro: None declared, maria giannotta: None declared, giulia righetti: None declared, Giuseppe Lopalco: None declared, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD

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.

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

Relationship Between Plasma Inflammatory Markers and Platelet Aggregation in Patients With Clopidogrel Resistance After Angioplasty

We evaluated the relationship between plasma inflammation markers and clopidogrel resistance in patients after stent implantation. The plasma levels of C-reactive protein (CRP), P-selectin, platelet soluble CD40 ligand (sCD40L), interleukin 6 (IL-6) and platelet aggregation were measured in 352 patients undergoing percutaneous coronary intervention (PCI) at baseline and after 6 months. The plasma levels of CRP, P-selectin, sCD40L, IL-6 was higher in 65 (18.5%) patients with clopidogrel resistance than in those with normal responsiveness at 6 months after PCI. There was a significant positive correlation between soluble CD40L levels and platelet aggregation ( r = .28, P < .05). Diabetes (DM) and sCD40L level were independent predictors for unresponsiveness after stent implantation according to stepwise multivariate analyses. The hazard ratio (HR) for sCD40L level was 3.02 (95% CI = 1.28 to 3.25; P = .036) and for DM 2.53 (95% CI = 1.28 to 6.55, P = .03). We conclude that sCD40L and DM may influence clopidogrel resistance.