Serum sCD163 Research Articles

Interaction of CD14 haplotypes and soluble CD14 on pulmonary function in agricultural workers

BackgroundAgricultural environments are contaminated with organic dusts containing bacterial components. Chronic inhalation of organic dusts is implicated in respiratory diseases. CD14 is a critical receptor for gram-negative lipopolysaccharide; however, its association with respiratory disease among agricultural workers is unknown. The objective of this study was to determine if serum soluble CD14 (sCD14) levels are associated with lung function among agricultural workers and if this association is modified by genetic variants in CD14.MethodsThis cross-sectional study included 584 veterans with >2 years of farming experience and that were between the ages of 40 and 80 years. Participants underwent spirometry and were genotyped for four tagging CD14 polymorphisms (CD14/-2838, rs2569193; CD14/-1720, rs2915863; CD14/-651, rs5744455; and CD14/-260, rs2569190). Serum sCD14 was assayed by ELISA.ResultsSubjects were 98% white males with a mean age 64.5 years. High soluble CD14 levels (> median sCD14) were associated decreased lung function (FEV1/FVC, p = 0.011; % predicted FEV1, p = 0.03). When stratified by COPD (yes/no) and smoking status (ever/never), high sCD14 levels (> median sCD14) were associated with low lung function among ever smokers with COPD (% predicted FEV1, padj = 0.0008; FEV1/FVC, padj = 0.0002). A similar trend was observed for never smokers with COPD; however, results did not reach statistical significance due to small sample size. There was a significant sCD14 x COPD/smoking interaction with lung function (% predicted FEV1, pinter = 0.0498; FEV1/FVC, pinter = 0.011). Regression models were adjusted for age, body mass index, education, sex, race and years worked on a farm. No association was found between CD14 polymorphisms/haplotypes (CD14/-2838; CD14/-1720; CD14/-651; CD14/-260) and sCD14 levels. The final model included the variables sCD14 and haplotypes and a haplotype x sCD14 interaction term. Individuals with the GTTG haplotype (CD14/-2838 → CD14/-260) and high sCD14 levels (> median sCD14) had on average 6.94 lower % predicted FEV1 than individuals with the GCCA haplotype and low sCD14 levels (≤ median sCD14, padj = 0.03).ConclusionCD14 haplotypes and sCD14 are important mediators of lung function among those with COPD in this occupationally-exposed population.

Role of Serum Soluble CD163 in the Diagnosis, Risk of Bleeding, and Prognosis of Gastro-Esophageal Varices in Cirrhotic Patients.

Research is continuous for noninvasive tools for the prediction of portal hypertension than upper gastrointestinal endoscopy. Serum sCD163 correlates with hepatic venous pressure gradient, aiding in the prediction of portal hypertension. We aimed at investigating the role of sCD163 in the prediction of the presence and size of varices as well as a stratification tool for surveillance or prophylaxis by assessment of prognosis and risk of bleeding. Two hundred forty-three cirrhotic patients were divided into 3 groups: group I: no varices, group II: small-sized varices, and group III: medium-sized and large-sized varices. Serum sCD163 levels were assessed and correlated with abdominal ultrasound and laboratory investigations. Follow-up for 1 year was conducted to assess the risk of bleeding, and band ligation was performed for significant varices with follow-up of obliteration. sCD163 levels were significantly higher in patients with varices requiring prophylactic interventions (P = 0.03) and in large varices (P = 0.012), patients at risk of bleeding (P = 0.04), and the bleeder patients (P = 0.001). No relationship between the sCD163 levels and the rate of variceal obliteration was reported. sCD163 levels were positively correlated with the Child score (P = 0.05), the portal vein diameter (P = 0.02), and the splenic size (P = 0.04). Although sCD163 level cannot predict the development of varices, it serves as a good predictor for the detection of size of varices (large varices), the need of prophylactic interventions, and risk of variceal bleeding. sCD163 level is a helpful indicator with the progression of cirrhosis and portal hypertension.

Sitagliptin but not alpha glucosidase inhibitor reduced the serum soluble CD163, a marker for activated macrophage, in individuals with type 2 diabetes mellitus.

Dipeptidyl peptidase-4 inhibitor (DPP-4i) is commonly used worldwide for the treatment of type 2 diabetes mellitus. In addition to its hypoglycemic activity, DPP-4i might have anti-inflammatory effects. In this study we examined the effects of DPP-4i on the serum levels of soluble CD163 (sCD163), a marker for activated macrophages, in individuals with type 2 diabetes mellitus. We compared these anti-inflammatory effects with those of α glucosidase inhibitor (αGI). Japanese patients with type 2 diabetes mellitus who were stably maintained on ≤2mg/day glimepiride alone were recruited and randomly assigned to receive additional sitagliptin (n=37) or αGI (n=37). Levels of sCD163 were measured before the addition and after a 24-week treatment period. Addition of sitagliptin significantly reduced the serum sCD163 (632 vs. 575ng/mL, p<0.05), while αGI did not display this effect (624 vs. 607ng/mL). The changes in levels of sCD163 were not related to changes in either HbA1c or body mass index (BMI). Our results suggested that DPP-4i might exert anti-inflammatory effects in individuals with type 2 diabetes mellitus, which are independent of its effects on glycemia and BMI.

Association of Macrophage Inflammation Biomarkers With Progression of Subclinical Carotid Artery Atherosclerosis in HIV-Infected Women and Men.

Monocytes and monocyte-derived macrophages promote atherosclerosis through increased inflammation and vascular remodeling. This may be especially true in chronic human immunodeficiency virus (HIV) infection. We examined 778 women (74% HIV+) in the Women's Interagency HIV Study and 503 men (65% HIV+) in the Multicenter AIDS Cohort Study who underwent repeated B-mode carotid artery ultrasound imaging in 2004-2013. We assessed baseline associations of the serum macrophage inflammation markers soluble (s)CD163, sCD14, galectin-3 (Gal-3), and Gal-3 binding protein (Gal-3BP) with carotid plaque formation (focal intima-media thickness >1.5 mm) over 7 years. Marker levels were higher in HIV+ persons versus HIV- persons. Presence of focal plaque increased over time: from 8% to 15% in women, and 24% to 34% in men. After adjustment for demographic, behavioral, and cardiometabolic factors, and CRP and interleukin-6, each standard deviation increase in sCD14 was associated with increased plaque formation (risk ratio [RR] 1.24, 95% confidence interval [CI] 1.07-1.43). This pattern was consistentby sex. sCD163 was associated with plaque formation in virally suppressed HIV+ men (RR 1.52, 95% CI 1.04-2.22); Gal-3BP and Gal-3 were not associated with increased plaque. sCD14 and sCD163 may play important roles in atherogenesis among HIV+ persons.

Diagnostic and prognostic value of CD163 for infection-associated hemophagocytic syndrome in children

Objective To investigate the diagnostic and prognostic value of serum soluble CD163 (sCD163) and the positive rate of membrane-bound CD163 (mCD163) in peripheral blood mononuclear cells (PBMC) in children with infection-associated hemophagocytic syndrome (IAHS). Methods Between July 2012 and June 2016, 26 pediatric patients with IAHS (IAHS group) and 28 pediatric patients with sepsis(sepsis group)admitted to Children′s Hospital Affiliated to Shanghai Jiaotong University were selected, and 20 healthy children were taken as healthy control group.Sandwich enzyme linked immunosorbent assay was used to detect serum sCD163.The population of circulating mCD163 positive monocytes was determined by using flow cytometry.Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic and prognostic values of sCD163 and mCD163 in children with IAHS compared with the diagnostic and prognostic values of plasma ferritin, and so on. Results The serum levels of sCD163 in patients of IAHS group, sepsis group and healthy control group were (1 264±538) mg/L, (862±332) mg/L, (610±316) mg/L, respectively.And the population of mCD163-positive PBMC in patients of IAHS group, sepsis group and healthy control group was (88.3±9.7)%, (68.5±18.3)%, (28.9±5.2)%, respectively.Both serum sCD163 and the population of mCD163-positive PBMC were significantly higher in IAHS group compared with those of sepsis group (t=2.031, P=0.048; t=3.191, P=0.002, respectively). The serum sCD163 and population of mCD163-positive PBMC in sepsis group were higher than controls (t=3.848, P=0.002; t=4.049, P=0.000, respectively). Moreover, the areas under the ROC curve (AUC) for the mCD163, sCD163, were 0.853(P=0.013), 0.762(P=0.004), 0.755(P=0.049), respectively.mCD163 at a cutoff of 83.7% had a high diagnosis sensitivity (81.8%) and specificity (72.4%). The optimal cutoff values of sCD163 and ferritin for predicting IAHS was 888 mg/L (sensitivity 66.7% and specificity 63.3%) and 2 880 μg/L (sensitivity 80.0% and specificity 54.5%). In addition, the serum level of sCD163 and the population of mCD163-positive PBMCs were significantly increased in acute phase and decreased in recovery phase[(1 553±542) mg/L vs. (866±92) mg/L, (91.0±6.4)% vs.(79.0±4.6)%, t=2.450, χ2=3.419, P=0.036, 0.007] in IAHS group.Furthermore, subgroup analysis indicated that the serum level of sCD163 and the population of mCD163-positive PBMCs were significantly higher in dead patients than those in survived patients [(1 748.91±518.17) mg/L vs.(909.69±171.35) mg/L, t=3.070, P=0.011; (93.50±8.42)% vs.(77.30±3.28)%, χ2=3.005, P=0.024, respectively]. Conclusion Serum sCD163 and the population of mCD163-positive PMSCs are specific and validity biomarkers for early diagnosis of IAHS, which also are associated with treatment response assessment and prognostic analysis in IAHS. Key words: Soluble CD163; Membrane-bound CD163; Infection-associated hemophagocytic syndrome; Sepsis; Child

Abstract WMP106: Soluble CD163 as a Prognostic Marker for Perihematomal Edema Formation and Functional Outcomes in Intracerebral Hemorrhage

Introduction: Macrophages are the predominant cell capable of removing toxic hemoglobin at sites of tissue injury, and CD163 has been recognized as the hemoglobin scavenger receptor present on the macrophage cell surface. In this study, we explored the levels of soluble CD163 (sCD163) in patients with intracerebral hemorrhage (ICH) to ascertain whether sCD163 was associated with clinicoradiologic features and long-term functional outcomes. Methods: Our ICH cohort was comprised of 50 patients with moderate-sized basal ganglia hematomas. We collected serial serum and cerebrospinal fluid (CSF) at pre-specified timepoints (24 hours, 48 hours, 3-5 days, 6-8 days, and greater than 10 days post-ictus). We also obtained samples from 10 healthy controls. Levels of sCD163 were measured by enzyme-linked immunosorbent assay. A linear mixed model was used to compare sCD163 values among various groups, using a Bonferroni correction for multiple test adjustment. The method of generalized estimating equations was used to determine associations with dichotomized outcomes (modified Rankin Scale score 0-3 versus 4-6). Results: Compared to healthy controls, serum sCD163 was higher in the ICH patients (40.6 versus 128.4 ng/mL). Within the ICH cohort, early values (24 hours to 5 days post-ictus) of serum sCD163 were significantly higher in patients who elaborated minimal perihematomal edema (PHE) (200.3 in patients with less than 10 mL PHE versus 71.8; p = 0.046). 6 to greater than 10 days post-ictus, sCD163 levels tailed off for patients with less PHE whereas levels rose in patients with greater PHE. Continued subacute elevation of sCD163, particularly in the CSF, was highly associated with poorer outcomes, both at discharge and at 90 days (p &lt; 0.001). These associations were independent of age, gender, peak hematoma volume, and ICH score; there was a statistically significant association of CSF sCD163 values with degree of intraventricular hemorrhage (p = 0.04). Conclusions: sCD163 may be a dynamic marker in ICH, with acute levels distinguishing edema patterns and subacute levels predicting functional outcome. Further studies are needed to confirm these findings and explore the pathophysiology behind these observations.

Clinical significance of soluble CD163 in polymyositis-related or dermatomyositis-related interstitial lung disease

BackgroundMacrophage activation is involved in the pathogenesis of polymyositis (PM)/dermatomyositis (DM). CD163, a scavenger receptor expressed on the surface of activated macrophages, mediates anti-inflammatory functions. This study aimed to evaluate the clinical significance of soluble CD163 (sCD163) in PM/DM-related interstitial lung disease (ILD).MethodsThe main subjects were 48 patients with PM/DM-related ILD. As controls, 10 patients with PM/DM without ILD and 20 healthy volunteers were enrolled. In patients with PM/DM-related ILD, the baseline characteristics and clinical course were obtained through a review of patient medical records. Serum sCD163 levels at ILD diagnosis were quantified by enzyme-linked immunosorbent assay, which were compared with the other baseline clinical factors and evaluated for potential as a prognostic biomarker. In addition, immunohistochemistry analysis using anti-human CD163 antibody was performed on the lung sections of two patients with DM-related ILD (a survivor and non-survivor, respectively) and one patient with early-stage lung cancer as a normal control.ResultsThe median value of serum sCD163 in patients with PM/DM-related ILD was 818 ng/mL, which was higher than that of PM/DM patients without ILD and healthy volunteers (716 ng/mL and 340 ng/mL, respectively). Significant but mild correlations with serum sCD163 levels were observed for serum C-reactive protein levels (r = 0.322) and % predicted forced vital capacity (r = −0.301) in patients with PM/DM-related ILD. A Cox proportional hazard model demonstrated that patients with PM/DM-related ILD and higher sCD163 levels had worse prognosis (age-adjusted and gender-adjusted hazard ratio per 100 ng/mL increase 1.27, 95% confidence interval 1.11–1.45, P <0.001). In immunohistochemistry analysis, compared with normal lung, alveolar infiltration of CD163-positive macrophages was evident in the lungs of patients with DM-related ILD. Especially, the finding was more severe in the non-survivor’s lung.ConclusionsSerum sCD163 might be a potential biomarker for predicting the severity and prognosis of PM/DM-related ILD. Our results suggest the importance of macrophage activation in the disease.

A possible interaction between periostin and CD163+ skin-resident macrophages in pemphigus vulgaris and bullous pemphigoid.

Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are autoimmune blistering diseases, and substantial numbers of CD163+ tissue-associated macrophages (TAMs) are detected in both diseases. PV and BP possess different subsets of helper T cells, suggesting that the cytokine profiles of PV and BP might be different. The purpose of this study was to investigate the microenvironment of lesional skin and serum of PV and BP patients, focusing on the immunomodulatory factors related to TAMs, such as periostin (POSTN), chemokines, cytokines and matrix metalloproteinases (MMPs). We first performed immunohistological staining of POSTN in PV and BP lesions. POSTN was prominent in the superficial dermis in both PV and BP lesions. Next, to validate the activation of CD163+ TAMs in PV and BP patients, we examined the serum levels of soluble (s)CD163. The serum sCD163 levels in PV and BP patients are significantly higher than in healthy controls. To further elucidate the molecular mechanisms of the effects of POSTN on CD163+ TAMs in PV and BP, we examined chemokines, MMPs and cytokines selected by DNA microarray database. The serum CXCL5 levels from PV patients are significantly higher than those in BP patients and healthy controls. The IL-36γ expression on infiltrating macrophages was prominent only in the lesional skin of PV, while the MMP12 deposition was detected in both PV and BP lesions. Our results shed light on the novel pathogenesis of PV through CD163+ TAMs.

HIV-associated changes in the enteric microbial community: potential role in loss of homeostasis and development of systemic inflammation.

Despite HIV therapy advances, average life expectancy in HIV-infected individuals on effective treatment is significantly decreased relative to uninfected persons, largely because of increased incidence of inflammation-related diseases, such as cardiovascular disease and renal dysfunction. The enteric microbial community could potentially cause this inflammation, as HIV-driven destruction of gastrointestinal CD4 T cells may disturb the microbiota-mucosal immune system balance, disrupting the stable gut microbiome and leading to further deleterious host outcomes. Varied enteric microbiome changes have been reported during HIV infection, but unifying patterns have emerged. Community diversity is decreased, similar to pathologies such as inflammatory bowel disease, obesity, and Clostridium difficile infection. Many taxa frequently enriched in HIV-infected individuals, such as Enterobacteriaceae and Erysipelotrichaceae, have pathogenic potential, whereas depleted taxa, such as Bacteroidaceae and Ruminococcaceae, are more linked with anti-inflammatory properties and maintenance of gut homeostasis. The gut viral community in HIV has been found to contain a greater abundance of pathogenesis-associated Adenoviridae and Anelloviridae. These bacterial and viral changes correlate with increased systemic inflammatory markers, such as serum sCD14, sCD163, and IL-6. Enteric microbial community changes may contribute to chronic HIV pathogenesis, but more investigation is necessary, especially in the developing world population with the greatest HIV burden (Video, Supplemental Digital Content 1, http://links.lww.com/COID/A15, which includes the authors' summary of the importance of the work).

CD30 Expression vs. Serum Soluble CD30 (sCD30) Level: Role in Prognosis and Treatment of Acute Myeloid Leukaemia

Objectives: As we noted that CD30 is a valuable molecule in regulation of growth and death of lymphocytes in malignant lymphomas, we analyzed CD30 expression and serum soluble CD30 (sCD30) molecule level in patients with acute myeloid leukemia (AML) to assess their role as a prognostic markers and to examine the possibility of anti-CD30 to be a targeted therapy in these patients.Methods: We studied CD30 expression by Multicolor flow cytometry immunophenotypic analysis on bone marrow aspirates of 50 AML patients. Serum sCD30 level was measured by Enzyme Linked Immunosrbent Assay (ELSA). We correlate CD30 and sCD30 values with all of white blood cell counts, Hemoglobin, platelets, bone marrow blasts and cytogenetics. The Fisher’s exact test or chi-square was used for comparison of categorical variables and the t-test or one-way analysis of variance (ANOVA) was applied for numerical comparisons using SPSS version 20. A p value of <0.05 was considered to be statistically significant.Results: Our study conducted on 50 AML patients, the mean patients’ age was 47.4 ± 18.1 years (range, 17-77), 11 (22%) were males and 39 (78%) were females. 16 (32%) patients have high CD30-expression and 11 (22%) have elevated serum sCD30. We found that there was a significant correlation between both CD30 expression and sCD30 level with WBCs count, BM blasts, Adverse risk cytogenetics, FLT3/ITD and with relapse for CD30 expression, complete remission failure with elevated serum sCD30 level.Conclusions: CD30 is expressed by myeloblasts in AML patients. We found that high CD30 expression and elevated sCD30 level can be used as prognostic markers for relapse and complete remission failure respectively. Furthermore, these patients with adverse risk cytogenetics have not too many treatment options, so the use anti- CD30 targeted therapy may be a possible alternative for this patient group which need further studies.

Dynamic Changes of the Frequency of Classic and Inflammatory Monocytes Subsets and Natural Killer Cells in Chronic Hepatitis C Patients Treated by Direct-Acting Antiviral Agents.

Objective Up to now, little was known about the immunological changes of chronic hepatitis C (CHC) patients treated with direct-acting antiviral agents (DAAs); we try to explore the effect of DAAs on the frequency of monocytes, NK cells, and cytokines that promote their activation. Methods 15 treatment-naive CHC patients and 10 healthy controls were recruited. Patients were examined before DAAs therapy (0 w) and at week 4 (4 w) and week 12 (12 w) of therapy. Percentage of monocytes and NK cells of the peripheral blood was analyzed by flow cytometry. Serum cytokines IL-12, IL-18, CXCL10, CXCL11, sCD14, and sCD163 were measured by enzyme linked immunosorbent assay. Results The frequency of CD3–CD16+CD56+ NK cells and classic CD14++CD16− monocytes decreased, while CD14+CD16+ monocytes and cytokines IL-12, IL-18, CXCL10, CXCL11, sCD14, and sCD163 increased at 0 w compared to healthy controls. During DAAs treatment, the decreased NK cells and classic monocytes gradually increased to normal levels; the increased inflammatory monocytes and cytokines IL-12 and CXCL11 decreased to normal levels, but the increased cytokines IL-18, CXCL10, sCD14, and sCD163 still remained at high levels at 12 w though they decreased rapidly from 0 w. Conclusion Our results showed that DAAs treatment attenuated the activation of monocytes and NK cells in CHC patients. Trial registration number is NCT03063723.

Can We Use Scd-163 in Combination with Other Noninvasive Fibrosis Markers to Predict Risky Esophageal Varices in Cirrhotics?

Background and aim: Still research is carried out for imaging and laboratory tools that can replace gastroscopy in esophageal varices prediction. Different non-invasive fibrosis predictors have shown promising results in predicting the presence of varices. In addition, serum sCD163 correlates with hepatic venous pressuregradient (HVPG). We had investigated different non-invasive tools for predicting the presence, size and/or bleeding risk of esophageal varices against gastroscopy as the gold standard as well as a stratification tool to identify patients who benefit from individualized surveillance or secondary prophylaxis.Methods: 243 cirrhotic patients were divided into three groups; group I: no varices, group II: small-sized varices, group III: mediumsized, large-sized and any size varices with risky signs. Assessment of sCD163 level, abdominal ultrasound and routine laboratory investigations were carried out. APRI, FIB-4, Lok’s score, Fibroindex, AAR and Platelet/spleen ratio were calculated and patients were monitored for one year. Band ligation was performed for significant varices and number of sessions and obliteration were recorded.Results: sCD163 levels were higher in patients having large varices (p=0.012), at risk of bleeding (p=0.04) and the bleeding patients (p=0.001). Lower albumin levels and platelets count, higher portal vein and splenic diameters, APRI, FIB4, Lok’s score, Fibroindex, AAR and platelet/spleen ratio were significant in patients with varices. Plt/spleen ratio had the best performance model in predicting varices using multivariate analysis with correct classification of 75.9%.Conclusion: Non-invasive fibrosis markers, especially the Plt/spleen diameter ratio; can predict the presence of esophageal varices; however, they still lack the specificity and sensitivity that make them replacing the screening endoscopy. Combining sCD163 to these tests may help in predicting bleeding risk. However, further studies are to be carved.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival.

Background We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Methods Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. Results We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day–6 months), late AR (>6 months), and early pyelonephritis (the 8th day–2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Conclusions Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

Evaluation of Prognostic Impact of Soluble CD14 in B-Chronic Lymphocytic Leukemia.

sCD14 is an acute phase reactant; few studies reported its prognostic value in B-CLL patients. This gave us the impetus to conduct this study. This study enrolled 40 newly diagnosed B-CLL Egyptian patients, presented to the Hematology Department of the Medical Research Institute in Alexandria University. The ZAP-70 was determined by flow cytometry whereas serum sCD14 concentration by human sCD14 sandwich ELISA method. The mean serum level of sCD14 was significantly higher among patients with positive ZAP-70, Binet stage C, Rai stage III-IV and high risk CLL prognostic index. It showed a significant positive correlation to the percentage of ZAP-70 expression and significant negative correlation to the hemoglobin concentration. Serum sCD14 concentration could be used to assess B-CLL patients initially as an additional prognostic marker, especially in low resources areas where flow cytometry is not available.

High soluble CD30 levels and associated anti-HLA antibodies in patients with failed renal allografts.

Serum soluble CD30 (sCD30), a 120-kD glycoprotein that belongs to the tumor necrosis factor receptor family, has been suggested as a marker of rejection in kidney transplant patients. The aim of this study was to evaluate the relationship between sCD30 levels and anti-HLA antibodies, and to compare sCD30 levels in patients undergoing hemodialysis (HD) with and without failed renal allografts and transplant recipients with functioning grafts. 100 patients undergoing HD with failed grafts (group 1), 100 patients undergoing HD who had never undergone transplantation (group 2), and 100 kidney transplant recipients (group 3) were included in this study. Associations of serum sCD30 levels and anti-HLA antibody status were analyzed in these groups. The sCD30 levels of group 1 and group 2 (154 ± 71 U/mL and 103 ± 55 U/mL, respectively) were significantly higher than those of the transplant recipients (group 3) (39 ± 21 U/mL) (p&lt;0.001 and p&lt;0.001). The serum sCD30 levels in group 1 (154 ± 71 U/mL) were also significantly higher than group 2 (103 ± 55 U/mL) (p&lt;0.001). Anti-HLA antibodies were detected in 81 (81%) and 5 (5%) of patients in groups 1 and 2, respectively (p&lt;0.001). When multiple regression analysis was performed to predict sCD30 levels, the independent variables in group 1 were the presence of class I anti-HLA antibodies (β = 0.295; p = 0.003) and age (β = -0.272; p = 0.005), and serum creatinine (β = 0.218; p = 0.027) and presence of class II anti-HLA antibodies (standardized β = 0.194; p = 0.046) in group 3. Higher sCD30 levels and anti-HLA antibodies in patients undergoing HD with failed renal allografts may be related to higher inflammatory status in these patients.

7 Association between low-dose aspirin use, monocyte biomarkers, matrix metalloproteinases and outcome in HFpEF

Introduction Most community heart failure patients present with preserved ejection fraction (HFpEF) associated with inflammation, monocytosis, endothelial dysfunction and platelet activation. We investigated the clinical relationship between low-dose aspirin and outcome in HFpEF and the effects of aspirin on monocyte function and cell-cell interactions in-vitro. Methods In a retrospective analysis of HFPEF patients, we identified 150 patients taking low-dose (75 mg/day) aspirin and age/sex-matched HFPEF controls not taking aspirin over a 3 year follow-up period. From this cohort, we also studied HFPEF age/sex-matched patients (14 aspirin, 14 non-aspirin) using primary monocyte isolation, monocyte qPCR, serum matrix metalloproteinase (MMP) and inflammatory marker assays. Finally, primary monocytes were isolated from 6 healthy volunteers, analysed using flow cytometry for monocyte-platelet complexes, monocyte chemotaxis assays, and co-cultured with platelet releasate (PR, 16h) with and without aspirin. Results Aspirin was associated with higher overall survival and lower HF hospitalisations over the 3-year follow up period (HR = 0.605, 95% confidence interval, 0.389–0.961). Serum MMP2 and sCD163 were significantly reduced in aspirin HFPEF versus matched HFPEF controls. The majority (88%) of donor monocytes were complexed with platelets. Monocyte incubation with PR caused cell activation, increased release of matrix metalloproteinas and MCP1 as well as increased monocyte invasiveness in an in-vitro transwell assay. Inflammatory cytokines (IL1alpha, IL1beta, CCL17) and gene expression of PSGL was reduced by aspirin as was monocyte invasion was reduced by 50% with aspirin treatment (p Conclusion This retrospective study shows an association between the use of low-dose aspirin and better clinical outcome in HFpEF, associated with reduced sCD163 and circulating matrix metalloproteinase. These effects may be related to antiplatelet mediated modulation of monocyte function. Further work is required to evaluate antiplatelet strategies in HFpEF.

Serum Soluble CD163 and its association with various disease parameters in patients with systemic sclerosis

Cluster of differentiation 163 (CD163) is a receptor that binds haptoglobin-hemoglobin complexes and is mainly expressed on macrophages and monocytes. As a result of shedding, the extracellular portion of CD163 circulates in the blood as a soluble CD163 (sCD163). This study aimed to measure serum sCD163 levels in patients with systemic sclerosis (SSc) and to assess its association with the clinical, laboratory, and radiological features of the disease. We measured serum sCD163 levels in 24 patients with SSc and in 30 healthy controls. Complete history of the patients was recorded and thorough clinical, rheumatological, and dermatological examinations were performed. For SSc, the skin thickness score was scored according to the modified Rodnan skin score method and pulmonary involvement was assessed in all patients using high-resolution computed tomography and by performing pulmonary function tests. The mean serum sCD163 levels in patients with diffuse and limited SSc (61.64±19.57 and 60.8±21.43 ng/mL, respectively) demonstrated a highly statistically significant increase compared with the mean serum levels in healthy controls (36.97±16.37 ng/mL) (p<0.001). Patients with SSc having elevated serum sCD163 levels had significantly higher pulmonary artery systolic pressure (PASP) than those with normal serum sCD163 levels (p<0.05). Furthermore, the serum sCD163 levels were significantly correlated with PASP (r=0.53, p<0.05) in patients with SSc. The mean serum sCD163 level in patients with SSc having digital ulceration (DU) (70.82±18.3 ng/mL) demonstrated a statistically significant increase (p<0.05) compared with that in SSC patients without DU (53.23±18.09 ng/mL). The elevated serum sCD163 levels in patients with SSc and its association with pulmonary hypertension suggest a possible role of macrophages in the pathogenesis and vascular involvement of SSc.

Stromal cells from inflamed lymph nodes modulate B cell surface CD23 expression

Abstract CD23 is a trans-membrane protein belonging to the C-type lectin family, widely expressed in the immune system. Originally identified as the low-affinity receptor for IgE, CD23 was later shown to also bind CD21, MHCII and various integrins, and to have pleiotropic roles, including modulation of cell proliferation, differentiation, Ig and cytokine secretion. Expression of membrane CD23 (mCD23) is regulated at least in part by its shedding from the cell surface via activity of metalloproteinases, the most important of which is ADAM10. Interestingly, secreted CD23 (sCD23) isoforms can exert immunomodulatory functions as soluble factors. B cells upregulate mCD23 and serum sCD23 levels have been found to be elevated in inflammatory and autoimmune conditions, including rheumatoid arthritis, and in B cell chronic lymphocytic leukemia. However, the mechanisms responsible for CD23 modulation on B cells are still unclear. Here we show that mCD23 is upregulated on mouse and human B cells found in inflamed lymphoid tissues. Furthermore, in vitro experiments demonstrate that B cell mCD23 upregulation is strictly dependent on soluble signals provided by stromal cells from inflamed, but not non-inflamed lymph nodes, and can be reversed by ADAM10-specific inhibitors. We propose therefore that the balance between B cell mCD23 and sCD23 expression in inflammatory conditions is modulated by microenvironmental signals provided by stromal cells within lymphoid tissues.

A Study of Serum Soluble CD 163 Levels in Women with Polycystic Ovary Syndrome.

The aim of this study was to determine serum soluble CD163 levels in patients with polycystic ovary syndrome and its relation to clinical and metabolic parameters. Eighty-four women aged 18-45 years, 43 with polycystic ovary syndrome and 41 controls were recruited in this case-control study. Serum sCD163 levels of the groups were compared. Other metabolic, hormonal, and clinical parameters including, body mass index, HOMA-IR, highly sensitive C- reactive protein, glucose, glycated hemoglobin, lipids, luteinizing hormone, and total testosterone and waist/hip circumference were also investigated. Patients were further subgrouped according to body mass index and sCD163 levels were investigated in obese and normal weight subjects. We performed a multiple regression analysis to investigate the independent predictors affecting soluble CD163 levels. Significantly higher soluble CD163 levels were found in patients with polycystic ovary syndrome (2.11±0.65 ng/ml vs. 1.69±0.85 ng/ml, p=0.012). We detected positive correlations of sCD163 with total testosterone, total cholesterol, and luteinizing hormone (r=0.330, p=0.002, r=0.356, p<0.001 and r=0.239, p=0.030, respectively). In the multiple linear regression analysis, total testosterone was the variable associated with the elevation of serum soluble CD163 levels. Soluble CD163, which is identified as a marker of inflammation and type II diabetes, is elevated in polycystic ovary syndrome. Elevated sCD163 levels were found to be associated with total testosterone. Further studies to elucidate the exact mechanism underlying the elevation of serum soluble CD163 in polycystic ovary syndrome are needed.

Association of CD30 transcripts with Th1 responses and proinflammatory cytokines in patients with end-stage renal disease

High serum sCD30 levels are associated with inflammatory disorders and poor outcome in renal transplantation. The contribution to these phenomena of transcripts and proteins related to CD30-activation and -cleavage is unknown. We assessed in peripheral blood of end-stage renal disease patients (ESRDP) transcripts of CD30-activation proteins CD30 and CD30L, CD30-cleavage proteins ADAM10 and ADAM17, and Th1- and Th2-type immunity-related factors t-bet and GATA3. Additionally, we evaluated the same transcripts and release of sCD30 and 32 cytokines after allogeneic and polyclonal T-cell activation. In peripheral blood, ESRDP showed increased levels of t-bet and GATA3 transcripts compared to healthy controls (HC) (both P<0.01) whereas levels of CD30, CD30L, ADAM10 and ADAM17 transcripts were similar. Polyclonal and allogeneic stimulation induced higher levels of CD30 transcripts in ESRDP than in HC (both P<0.001). Principal component analysis (PCA) in allogeneic cultures of ESRDP identified two correlation clusters, one consisting of sCD30, the Th-1 cytokine IFN-γ, MIP-1α, RANTES, sIL-2Rα, MIP-1β, TNF-β, MDC, GM-CSF and IL-5, and another one consisting of CD30 and t-bet transcripts, IL-13 and proinflammatory proteins IP-10, IL-8, IL-1Rα and MCP-1. Reflecting an activated immune state, ESRDP exhibited after allostimulation upregulation of CD30 transcripts in T cells, which was associated with Th1 and proinflammatory responses.