Serum Soluble CD14 Research Articles

Clinical significance of serum soluble scavenger receptor CD163 in patients with lupus nephritis.

The soluble CD163 (sCD163) was elevated in systemic lupus erythematosus (SLE) patients. To study whether serum sCD163 could be used to predict the occurrence and prognosis of lupus nephritis (LN). The recruited patients were classified into different groups according to standard identification criteria. The patients with LN. 11 indices were analyzed and compared in SLE and LN patients. Furthermore, the level of serum sCD163 was detected using an enzyme-linked immunosorbent assay. Meanwhile, the receiver operating characteristic analysis was performed to evaluate the prediction effect of sCD163. Additionally, spearman correlation analysis of serum sCD163 with indices was conducted. There were six positive indices and one negative risk factor correlated to LN. sCD163 was elevated in LN patients and could be used to diagnose LN. Importantly, sCD163 was increased in LN patients with a heavy SLE disease activity index. Finally, it was revealed that the level of sCD163 was higher in the LN patients with no response than that with complete or partial response, which also could predict the prognosis of LN. Serum sCD163 was elevated in LN patients than in SLE patients, which could be used to predict the occurrence and prognosis of LN.

Serum-Soluble CD163 Levels as a Prognostic Biomarker in Patients with Diffuse Large B-Cell Lymphoma Treated with Chemoimmunotherapy.

The majority of patients with Diffuse Large B-cell Lymphoma (DLBCL) will respond to first-line treatment and be cured. However, the disease is heterogeneous, and biomarkers able to discriminate patients with suboptimal prognosis are needed. M2 CD163-positive tumor-associated macrophages (TAMs) were shown to be implicated in DLBCL disease activity regulation. Serum-soluble CD163 (sCD163) functions as a scavenger receptor for haptoglobin-hemoglobin complexes and is mostly expressed by monocytes and macrophages. Its levels are used to determine macrophage activation. We aimed to determine serum sCD163 in a sample of DLBCL patients and study eventual correlations with parameters of disease activity or survival. Serum sCD163 levels were measured in 40 frozen sera from patients diagnosed with DLBCL and 30 healthy individuals (HIs) using an enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using SPSS version 28. The results showed that patients who achieved complete response after standard-of-care immunochemotherapy and were alive and disease-free after 12 months of follow-up but had elevated sCD163 levels (above median) at diagnosis presented a significantly worse overall survival compared to those with initial serum sCD163 levels below the median (p = 0.03). Consequently, serum sCD163 levels in patients with DLBCL may constitute a marker of long-term response to chemoimmunotherapy.

The beneficial effect of probiotics as an adjuvant treatment in childhood drug resistant epilepsy: A prospective pilot study.

One of the most common long-term neurological disorders affecting children is epilepsy. Even with effective antiseizure medications, one-third of epileptic patients develop drug-resistant epilepsy (DRE). Numerous treatments have been offered to these DRE patients, though with varying degrees of effectiveness. This study aimed to evaluate the effectiveness of probiotics in improving the quality of life (QoL) and lowering the severity and frequency of epileptic episodes in DRE patients. As well as to assess the anti-inflammatory effects of probiotics. DRE patients were daily supplemented with one probiotic for 4months. During these 4months, patients continued their routine anti-epileptics with no change in the doses. Before and following the 4-month trial, patients had their QoL evaluated using the validated Arabic version of QoL in epilepsy-31 inventory (QoLIE-31) questionnaire, an electroencephalogram (EEG) examination, and serum soluble CD14 (sCD14) evaluation by ELISA. Of the 21 DRE patients who completed the study, 42.9% achieved the therapeutic goal, which was a ≥50% reduction in seizures. After probiotic, there was a significant increase in time elapsed since the last seizure (p = 0.001) and a decrease in seizure duration (p = 0.038), frequency (p = 0.002), and severity by Chalfont Seizure Severity Score (p < 0.001), as compared to pre-probiotic data. Moreover, there was a significant decrease in serum levels of sCD14 (p < 0.001) and a significant improvement in QoL (p < 0.05). Probiotics may be used as a DRE adjuvant treatment. They can lessen the number and severity of seizures, alleviate the associated inflammation, and enhance the QoL for DRE patients.

Insights into the associations between the gut microbiome, its metabolites and heart failure.

Heart failure (HF) is the end stage of most cardiovascular diseases and remains a significant health problem globally. We aimed to assess whether patients with left ventricular ejection fraction ≤45% had alterations in both the gut microbiome profile and production of associated metabolites when compared to a healthy cohort. We also examined the associated inflammatory, metabolomic, and lipidomic profiles of HF patients. This single centre, observational study, recruited 73 HF patients and 59 healthy volunteers. Blood and stool samples were collected at baseline and 6-month follow-up, along with anthropometric and clinical data. Compared to healthy controls, HF patients had reduced gut bacterial alpha diversity at follow-up (p =0.004) but not at baseline. The stool microbiota of HF patients was characterized by a depletion of operational taxonomic units representing commensal Clostridia at both baseline and follow-up. HF patients also had significantly elevated baseline plasma acetate (p =0.007), plasma TMAO (p =0.003), serum sCD14 (p =0.005) and sCD163 (p =0.004) levels compared to healthy controls. Furthermore, HF patients had a distinct metabolomic and lipidomic profile at baseline when compared to healthy controls. Differences in the composition of the gut microbiome and the levels of associated metabolites were observed in patients with HF when compared to a healthy cohort. This was also associated with an altered metabolomic and lipidomic profile. Our study identifies microorganisms and metabolites that could represent new therapeutic targets and diagnostic tools in the pathogenesis of HF.

Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine-associated myocarditis.

Rare immune-mediated cardiac tissue inflammation can occur after vaccination, including after SARS-CoV-2 mRNA vaccines. However, the underlying immune cellular and molecular mechanisms driving this pathology remain poorly understood. Here, we investigated a cohort of patients who developed myocarditis and/or pericarditis with elevated troponin, B-type natriuretic peptide, and C-reactive protein levels as well as cardiac imaging abnormalities shortly after SARS-CoV-2 mRNA vaccination. Contrary to early hypotheses, patients did not demonstrate features of hypersensitivity myocarditis, nor did they have exaggerated SARS-CoV-2-specific or neutralizing antibody responses consistent with a hyperimmune humoral mechanism. We additionally found no evidence of cardiac-targeted autoantibodies. Instead, unbiased systematic immune serum profiling revealed elevations in circulating interleukins (IL-1β, IL-1RA, and IL-15), chemokines (CCL4, CXCL1, and CXCL10), and matrix metalloproteases (MMP1, MMP8, MMP9, and TIMP1). Subsequent deep immune profiling using single-cell RNA and repertoire sequencing of peripheral blood mononuclear cells during acute disease revealed expansion of activated CXCR3+ cytotoxic T cells and NK cells, both phenotypically resembling cytokine-driven killer cells. In addition, patients displayed signatures of inflammatory and profibrotic CCR2+ CD163+ monocytes, coupled with elevated serum-soluble CD163, that may be linked to the late gadolinium enhancement on cardiac MRI, which can persist for months after vaccination. Together, our results demonstrate up-regulation in inflammatory cytokines and corresponding lymphocytes with tissue-damaging capabilities, suggesting a cytokine-dependent pathology, which may further be accompanied by myeloid cell-associated cardiac fibrosis. These findings likely rule out some previously proposed mechanisms of mRNA vaccine--associated myopericarditis and point to new ones with relevance to vaccine development and clinical care.

Abstract P5-02-42: Soluble CD163 may be a predictive biomarker of the efficacy of nivolumab plus chemotherapy in patients with HER2-negative metastatic breast cancer (WJOG9917BTR)

Abstract Background: We have conducted a phase II trial (WJOG9917B) to evaluate efficacy of triple therapy with nivolumab, paclitaxel and bevacizumab in patients (pts) with HER2-negative metastatic breast cancer (MBC). Although soluble CD163 has been reported as a potential biomarker for predicting the efficacy of nivolumab in melanoma, however the data is limited in breast cancer. In an ancillary study (WJOG9917BTR), serum level of soluble CD163 were evaluated to elucidate this question. Methods: The main study enrolled 57 pts and showed that median Progression-free survival (PFS) and overall survival (OS) was 14.0 months and 32.5 months, respectively, with a median follow-up of 29.5 months. We have collected blood samples from consenting patients. Serum samples were collected at pretreatment, cycle 1 day 8 and other time points, which were used to measure the concentrations of cytokines, chemokines, and other surrogate proteins. PFS, OS, and response were analyzed in association with the biomarker data using the Kaplan–Meier method, log-rank tests as appropriate. Results: Biomarker study included 50 pts (36 with recurrent BC and 14 with de novo stage IV BC). The median amount of soluble CD163 before treatment was 562.3 (pg/ml) (range: 158.7-1518.0), and the baseline CD163 levels were higher in pts with recurrent than de novo stage IV (p = 0.0099). Other clinical factors including tumor subtypes, liver metastasis, response, PFS or OS were not significantly associated with the baseline CD163 levels. The kinetic changes in serum soluble CD163 after treatment were divided into two groups; one group (30 patients, CD163 increased group) had increased soluble CD163 immediately after administration (Cycle 1 Day 8), with a median PFS of 18.2; the other group (20 patients, CD163 decreased group) had decreased CD163 immediately after administration, with a median PFS of 13.6. There was a significantly difference in PFS between these two groups (hazard ratio 0.50 [0.26-0.93], log-rank test, p = 0.0263), but not in OS (p = 0.0548). These results suggested that the early change of serum soluble CD163 may be a predictive biomarker of efficacy of nivolumab plus chemotherapy in pts with HER2-negative MBC. Conclusions: Soluble CD163 may be a predictive biomarker for early detection of the efficacy of nivolumab plus chemotherapy in pts with HER2-negative MBC. (UMIN000029590) Citation Format: Toru Mukohara, Yukinori Ozaki, Shigehisa Kitano, Makiko Yamashita, Daiki Ikarashi, Junji Tsurutani, Tsutomu Iwasa, Masato Takahashi, Norikazu Masuda, Manabu Futamura, Hironobu Minami, Koji Matsumoto, Yuko Tanabe, Hidetaka Kawabata, Kenichi Yoshimura, Toshimi Takano. Soluble CD163 may be a predictive biomarker of the efficacy of nivolumab plus chemotherapy in patients with HER2-negative metastatic breast cancer (WJOG9917BTR). [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-42.

The significance of CD14 in clear cell renal cell carcinoma progression and survival prognosis

Purpose: CD14-positive tumour and immune cells have been implicated in cancer progression. This study evaluated the prognostic significance of CD14 immunostaining in clear cell renal cell carcinoma (ccRCC) compared to the adjacent non-cancer kidney, and serum soluble CD14 (sCD14) levels in patients versus controls. Methods: Immunohistochemistry was performed for CD14 on ccRCC and the corresponding adjacent non-cancer kidney tissue from 88 patients. Staining intensity was determined using Aperio ImageScope morphometry. Serum sCD14 was evaluated for 39 ccRCC patients and 38 non-cancer controls using ELISA. CD14 levels were compared with tumour characteristics and survival status. Results: CD14 overall and nuclear immunostaining was higher in ccRCC compared to the adjacent non-cancer kidney tissue. CD14 nuclear immunostaining in the adjacent non-cancer kidney was significantly associated with advanced stage and adverse RCC survival prognosis. Serum sCD14 concentration was elevated in ccRCC patients compared to non-cancer controls and was also significantly associated with tumour stage and worse survival prognosis. Higher CD14 expression, in particular CD14 positive immune cell infiltrates found in the adjacent non-RCC kidney tissue, were associated with tumour progression and poorer prognosis. Conclusion: The levels of CD14 in non-RCC adjacent kidney and serum could be potential prognostic indicators.

Leaky Gut and Severe Adverse Events in Advanced Hepatocellular Carcinoma Treated With Lenvatinib.

To identify predictors of severe adverse events (≥grade 3) in patients with advanced hepatocellular carcinoma treated with lenvatinib. Of 41 patients, 25 and 16 were stratified into the severe and non-severe adverse events groups, respectively. Of these, 19 formed a lactulose-mannitol test subgroup, which was divided into severe adverse events (n=11) and non-severe adverse events (n=8) groups. Severe adverse events were assessed by liver disease etiology and modified albumin-bilirubin grade. Intestinal permeability by lactulose-mannitol test and serum soluble CD163, soluble mannose receptor, and zonulin levels. Severe adverse event incidence rates were higher in patients with advanced hepatocellular carcinoma related to alcoholic liver disease and nonalcoholic fatty-liver disease than in those with advanced hepatocellular carcinoma of other etiologies (p=0.014). The rates were higher for modified albumin-bilirubin grades 2a and 2b compared to modified albumin-bilirubin grade 1 (p=0.0104). Zonulin levels were higher in the severe adverse event group (p=0.0331) and were independently associated with severe adverse events (odds ratio=140, 95% confidence interval=1.66-11800; p=0.029). Patients with high zonulin levels (≥0.518 ng/ml) experienced more severe adverse events than those with low levels (<0.518 ng/ml) (p=0.0137). In the lactulose-mannitol test subgroup, the urine lactulose:mannitol ratio was higher in the severe vs. non-severe adverse event group (p=0.0164). Moreover, it was higher in patients with alcoholic liver disease and nonalcoholic fatty-liver disease-related advanced hepatocellular carcinoma compared to those with other advanced hepatocellular carcinoma etiologies (p=0.0108). Serum zonulin levels predict severe adverse events in patients with advanced hepatocellular carcinoma treated with lenvatinib.

Serum Soluble CD163 as a Marker of Activity in MS Patients

Serum Soluble CD163 as a Marker of Activity in MS Patients

Up-regulated serum levels of soluble CD25 and soluble CD163 in pediatric patients with SARS-CoV-2

Similar to hemophagocytic lymphohistiocytosis (HLH), some patients with SARS-CoV-2 have cytokine storm. Serum soluble interleukin-2 receptor (sCD25) and soluble CD163 (sCD163) are potential diagnostic biomarkers for HLH that help in guiding its treatment. This study was the first to investigate serum sCD25 and sCD163 levels in SARS-CoV-2. Serum sCD25 and sCD163 were measured by ELISA in 29 patients with SARS-CoV-2, aged between 2 months and 16 years (13 had COVID-19 and 16 had multisystem inflammatory syndrome in children (MIS-C)), in comparison to 30 age- and sex-matched healthy control children and 10 patients with HLH. Levels of these markers were re-measured in 21 patients with SARS-CoV-2 who were followed up 3 months after recovery. Patients with SARS-CoV-2 had significantly higher serum sCD25 and sCD163 than healthy control children (P < 0.001). SARS-CoV-2 patients had significantly higher sCD25 than patients with HLH (P < 0.05). Serum sCD25 was a good differentiating marker between patients with SARS-CoV-2 and HLH. Although there was a significant decrease of serum sCD25 and sCD163 of the 21 SARS-CoV-2 patients who were followed up, these levels were still significantly higher than the healthy controls levels (P < 0.001). Conclusion: Serum sCD25 and sCD163 levels were up-regulated in SARS-CoV-2 patients. Serum sCD25 was a good differentiating marker between SARS-CoV-2 and HLH. This initial report requires further studies, on large scales, to investigate the relationship between SARS-CoV-2 and both sCD25 and sCD163, including the disease severity and outcome. The therapeutic role of sCD25 and sCD163 antagonists should also be studied in SARS-CoV-2 patients.What is Known:• Similar to hemophagocytic lymphohistiocytosis (HLH), some patients with COVID-19 have cytokine storm due to excessive pro-inflammatory host response.• Serum soluble interleukin-2 receptor (sCD25) and soluble CD163 (sCD163) are potential diagnostic biomarkers for HLH. Monitoring of serum sCD25 and sCD163 levels can also help in guiding the treatment.What is New:• Serum sCD25 and sCD163 levels are up-regulated in patients with COVID-19, including patients presenting with multisystem inflammatory syndrome in children (MIS-C).• Serum sCD25 is a good differentiating marker between SARS-CoV-2 and HLH.

Prognostic Utility of Serum TARC, MDC, IL10, and Soluble CD163 Levels with Positron Emission Tomography (PET) Response-Adapted Therapy for Advanced-Stage Hodgkin Lymphoma (HL): a SWOG S0816 US Intergroup Correlative Study

Prognostic Utility of Serum TARC, MDC, IL10, and Soluble CD163 Levels with Positron Emission Tomography (PET) Response-Adapted Therapy for Advanced-Stage Hodgkin Lymphoma (HL): a SWOG S0816 US Intergroup Correlative Study

Serum Soluble CD163 as a Predictor of Esophageal Varices and Variceal Bleeding in Cirrhotic Patients

ABSTRACT Background: Bleeding of esophageal varices (OV) is also bearing elevated mortality in patients with liver cirrhosis (LC). The best standard diagnostic investigation for OV is upper gastrointestinal (GI) endoscopy. Patients and endoscopic units alike are burdened by the endoscopic screening of all patients with liver cirrhosis. The use of non-invasive OV detection reduces the need for endoscopic screening. Objective: The aim of the current work was to test serum soluble CD 163(sCD163) as a predictor of the presence, and grade of OV and as non-invasive indicator of having severe variceal bleeding. Patients and Methods: This cross-sectional study included a total of 70 cirrhotic patients, attending at the Hepatology and Gastroenterology Unit, Department of Internal Medicine, Benha University Hospital, Egypt. To detect OV, all patients underwent upper GI endoscopy, and serum sCD163 levels were assessed using an ELISA technique. Results: Patients with OV had a higher mean value of sCD163 levels (8.71±8.42 ng/ml) than patients without OV (2.89±1.02 ng/ml), however this was not statistically significant (P=0.13). sCD163 level was significantly higher in large OV group (10.75±9.26 ng/ml) than small OV group (3.75±0.92 ng/ml), (P=0.001). The rate of significant variceal bleeding is closely linked to serum higher sCD163 levels more than (4.63 ng/ml). Conclusion: It could be concluded that serum sCD163 could be a non-invasive indicator of the presence of OV in cirrhotic patients. It may also be used for the prediction of the size of OV and the probability of severe variceal bleeding.

Diagnostic and prognostic value of serum soluble CD163 in cirrhotic patients with hepatitis C virus-related hepatocellular carcinoma before and after locoregional therapy

BackgroundTumor-associated macrophages (TAMs), inflammatory cells in tumor microenvironment, are crucial for the tumor occurrence and progression which in turn increase the expression of soluble CD163 (sCD163). Nevertheless, not much has been established regarding sCD163 and its connection to HCC diagnosis and prognosis. This study was conducted to evaluate the diagnostic and prognostic role of sCD163 in patients with HCC on top of HCV-related liver cirrhosis. Forty adult patients with HCV-related liver cirrhosis and HCC (HCC group) were randomly selected and subjected to locoregional therapies, either transarterial chemoembolization (TACE) or radiofrequency ablation (RFA). Four patients were excluded because of portal vein invasion. Another group of 20 patients with liver cirrhosis only served as controls (LC group). Routine laboratory studies and abdominal ultrasound were done for all. Alpha-fetoprotein (AFP) and sCD163 were measured twice, at baseline and 1-month post-intervention, using a commercially available enzyme-linked immunosorbent assay kit.ResultsAt baseline, sCD163 showed an insignificant higher value in HCC group (p > 0.05). The best cutoff value for sCD163 and AFP was 6.2 mg/L and 195 ng/mL, respectively. AFP had a larger area under the curve (0.88 vs. 0.767). An overall significant decline was seen in sCD163 after treatment (6.5±1.5 to 3.1±2.5 mg/L; p < 0.001), while AFP showed an insignificant decrease (p > 0.05). Also, sCD163 decreased significantly in the eradicated cases (6.1±1.4 mg/L before intervention vs. 2.3±1.4 mg/L after intervention, p < 0.01), while there was a significant increase in the recurrent cases (8.4±0.4 mg/L before intervention vs. 10.3±1.6 after intervention; p < 0.05). Moreover, sCD163 showed a significant difference in its pre-intervention and post-intervention values between recurrent and eradicated HCC cases (p < 0.01).ConclusionsIt is concluded that sCD163 has a minor role as a diagnostic marker for HCC, yet it could be used as a good prognostic marker in predicting the tumor response to locoregional therapies.

Accuracy of serum procalcitonin, C-reactive protein and soluble CD14 subtype levels in diagnosis of sepsis in children

Background/Aim. Despite the widespread use of procalcitonin, C-reactive protein (CRP), and soluble CD14 subtype (sCD14-ST), their diagnostic accuracy in children with sepsis is not yet clear. The aim of the study was to establish and compare the diagnostic accuracy of procalcitonin, CRP, and sCD14-ST in children admitted to the hospital under suspicion of having sepsis. Methods. The study was designed as a retrospective cross-sectional study on children admitted to the Pediatrics Clinic in Kragujevac, Serbia, under suspicion of sepsis, during a 6-month period. Diagnostic accuracy was tested by the construction of receiver operating characteristic (ROC) curves and their comparison in terms of area under the curve (AUC). Results. Procalcitonin had the largest AUC [0.75; 95% confidence interval (CI) 0.63?0.88], followed by CRP (0.68; 95% CI 0.54?0.81) and sCD14-ST (0.65; 95% CI 0.52 ? 0.79). Differences between the areas under the ROC curves were not significant (CRP vs. procalcitonin z = 1.054, p = 0.291; CRP vs. sCD14-ST z = 0.238, p = 0.812; procalcitonin vs. sCD14-ST z = 1.089, p = 0.286). Conclusion. Our study showed relatively low sensitivity and moderate specificity of procalcitonin, C-reactive protein and sCD14-ST in diagnosing sepsis among children, as well as similar diagnostic accuracy of the three biomarkers.

CD14+ monocytes and CD163+ macrophages correlate with the severity of liver fibrosis in patients with chronic hepatitis C.

Hepatic fibrosis is a crucial pathological process involved in the development of chronic hepatitis C (CHC) and may progress to liver cirrhosis and hepatocellular carcinoma. Activated peripheral blood monocytes and intrahepatic macrophages further promote hepatic fibrogenesis by releasing proinflammatory and profibrogenic cytokines. The present study aimed to investigate the role of peripheral CD14+ monocytes and intrahepatic CD163+ macrophages in hepatitis C virus (HCV)-associated liver fibrosis and clarify whether serum soluble CD163 (sCD163) may serve as a fibrosis marker in patients with CHC. A total of 87 patients with CHC and 20 healthy controls were recruited. Serum sCD163 levels were measured by ELISA. Frequencies of peripheral CD14+ monocytes and inflammatory cytokines expressed by CD14+ monocytes were analyzed by flow cytometry. The degree of fibrosis in human liver biopsies was graded using the Metavir scoring system and patients were stratified into two groups based on those results (F<2 vs. F≥2). Hepatic expression of CD163 was examined by immunohistochemical staining. The diagnostic values of sCD163, aspartate aminotransferase to platelet ratio index (APRI), fibrosis 4 score (FIB-4) and the aspartate aminotransferase to alanine aminotransferase ratio (AAR) in significant fibrosis (F≥2) were evaluated and compared using receiver operating characteristic (ROC) curves. The results indicated that the serum sCD163 levels and the frequency of CD14+ monocytes were significantly higher in the patients than that in the controls and positively correlated with liver fibrosis. The level of serum sCD163 was consistent with hepatic CD163 expression in the liver sections from patients. The frequencies of interleukin (IL)-8- and tumor necrosis factor-α-expressing monocytes were increased and that of IL-10-expressing monocytes was decreased in the patients. The area under the ROC curve (AUROC) for sCD163, APRI, FIB-4 and AAR was 0.876, 0.785, 0.825 and 0.488, respectively, and the AUROC for sCD163 was significantly higher than those for APRI and AAR. In conclusion, sCD163 may serve as a novel marker for assessing the degree of liver fibrosis in HCV-infected patients.

Increased macrophage activation marker soluble CD163 is associated with graft dysfunction and metabolic derangements in renal transplant recipients

BackgroundRenal allograft is vulnerable to numerous insults and is associated with metabolic derangements. Macrophages are regulators of inflammation and play a role in obesity, lipid metabolism and insulin resistance (IR). The present study was designed to assess macrophage activation, reflected by serum soluble CD163 (sCD163), in renal transplant recipients (RTR) and its relation to chronic allograft dysfunction (CAD) and metabolic derangements. MethodsFifty recipients of renal transplantation (RT) [22 with stable renal function and 28 with CAD] and 20 age- and sex-matched healthy controls were enrolled in the study. Serum sCD163 and high sensitivity C-reactive protein (hsCRP) were measured using enzyme-linked immunosorbent assay. Anthropometric measurements, renal function, lipid profile and homeostatic model assessment of IR (HOMA-IR) were estimated. Renal interstitial fibrosis (IF) was graded in renal biopsies of CAD. ResultsRTR mean age was 38.84 ± 9.28 years and 83% of them were males. Post-transplant dyslipidemia, diabetes and IR (HOMA-IR >2) were present in 42%, 24% and 86% of RTR respectively. Serum sCD163 levels were significantly higher in RTR with stable renal function and CAD than in healthy controls (814.41 ± 59.62 ng/ml and 1021.21 ± 120.82 ng/ml vs. 602.90 ± 114.98 ng/ml respectively) and in RTR with CAD than in patients with stable renal function (p < 0.001). Serum sCD163 levels were positively correlated with body mass index, waist-to-hip ratio, worsening renal function, dyslipidemia, HOMA-IR and serum hsCRP in RTR and with the degree of renal IF in RTR with CAD (p < 0.05). ROC curve showed that serum sCD163 was superior to serum hsCRP in detecting CAD after RT (AUC = 0.972 vs. 0.753 respectively, p = 0.001). ConclusionMacrophage activation, reflected by increased circulating sCD163, may play a role in the development of CAD and metabolic derangements after RT. Serum sCD163 could be a potential biomarker for renal allograft dysfunction.

Serum biomarker CD163 predicts overall survival in patients with pancreatic ductal adenocarcinoma

Abstract The serum soluble CD163 (sCD163) is elevated in patients with inflammatory disease and several types of cancer. However, the prognostic value of serum sCD163 in pancreatic ductal adenocarcinoma (PDAC) has not yet been investigated. In this study, serum level of sCD163 was measured by using the peripheral blood of 54 patients with PDAC, 20 patients with benign tumor of pancreas, and 30 healthy volunteers (healthy controls). The association between serum sCD163 level and overall survival was analyzed. Receiver operating characteristic (ROC) curves were generated, and areas under the curve (AUC) were compared to evaluate the diagnostic accuracy, including CA 19-9, CEA, CA 125, CA 153, and serum sCD163 level. Serum sCD163 level of patients with PDAC was significantly higher than patients with benign tumor (P = .002) and health controls (P &lt; .001). Using ROC curves, we found that the AUC values of serum sCD163 were higher than those of CA 125 and CA 153, but lower than those of CA 19-9 and CEA. Serum sCD163 was negatively correlated with lymphocyte to monocyte ratio (LMR; r = −0.428, P = .001). In addition, the prognosis of PDAC patients with sCD163 ≥ median was worse than sCD163 &lt; median by using univariate analysis (P = .027). Further, multivariate analysis showed that higher level of serum sCD163 was still associated with poorer overall survival (P = .020). In conclusion, the serum sCD163 has the potential as a new promising parameter to predict the prognosis in PDAC patients.

Soluble CD14 Subtype in Peripheral Blood is a Biomarker for Early Diagnosis of Sepsis.

To study the value of serum soluble CD14 subtype (sCD14-ST) in early diagnosis of sepsis. Seventy-two patients were diagnosed with systemic inflammatory response syndrome, sepsis, or septic shock. Peripheral blood was collected at 0, 12, 24, and 48 hours after admission to the hospital. Levels of sCD14-ST, procalcitonin (PCT), hypersensitive C-reactive protein (CRP), and white blood cells (WBC) were determined. Levels of sCD14-ST in the patients with septic shock were higher than those in the other patients (P < .01) and peaked at 48 h. PCT and CRP levels were similar in the patients at admission but increased by 5 times to 10 times in the next 48 h, especially in the patients with septic shock. WBC levels remained high and did not change dramatically. Receiver operating characteristic analysis revealed that the area under the curve, sensitivity, and specificity values of sCD14-ST to diagnose sepsis were much higher than those of the other markers. Compared with PCT, CRP, and WBC, sCD14-ST is a better biomarker for the early diagnosis of sepsis.

Wheat Consumption Leads to Immune Activation and Symptom Worsening in Patients with Familial Mediterranean Fever: A Pilot Randomized Trial.

We have identified a clinical association between self-reported non-celiac wheat sensitivity (NCWS) and Familial Mediterranean Fever (FMF). Objectives: A) To determine whether a 2-week double-blind placebo-controlled (DBPC) cross-over wheat vs. rice challenge exacerbates the clinical manifestations of FMF; B) to evaluate innate immune responses in NCWS/FMF patients challenged with wheat vs. rice. The study was conducted at the Department of Internal Medicine of the University Hospital of Palermo and the Hospital of Sciacca, Italy. Six female volunteers with FMF/NCWS (mean age 36 ± 6 years) were enrolled, 12 age-matched non-FMF, NCWS females, and 8 sex- and age-matched healthy subjects served as controls. We evaluated: 1. clinical symptoms by the FMF-specific AIDAI (Auto-Inflammatory Diseases Activity Index) score; 2. serum soluble CD14 (sCD14), C-reactive protein (CRP), and serum amyloid A (SSA); 3. circulating CD14+ monocytes expressing interleukin (IL)-1β and tumor necrosis factor (TNF)-α. The AIDAI score significantly increased in FMF patients during DBPC with wheat, but not with rice (19 ± 6.3 vs. 7 ± 1.6; p = 0.028). sCD14 values did not differ in FMF patients before and after the challenge, but were higher in FMF patients than in healthy controls (median values 11357 vs. 8710 pg/ml; p = 0.002). The percentage of circulating CD14+/IL-1β+ and of CD14+/TNF-α+ monocytes increased significantly after DBPC with wheat vs. baseline or rice challenge. Self-reported NCWS can hide an FMF diagnosis. Wheat ingestion exacerbated clinical and immunological features of FMF. Future studies performed on consecutive FMF patients recruited in centers for auto-inflammatory diseases will determine the real frequency and relevance of this association.

Rifaximin Alleviates Endotoxemia with Decreased Serum Levels of Soluble CD163 and Mannose Receptor and Partial Modification of Gut Microbiota in Cirrhotic Patients.

Rifaximin is a poorly absorbable antibiotic against hepatic encephalopathy (HE). This observational study aimed to elucidate the effect of rifaximin on intestinal permeability and gut microbiota in patients with decompensated cirrhosis. Thirty patients with decompensated cirrhosis were assessed by ammonia level, neuropsychological testing, endotoxin activity (EA), and serum proinflammatory cytokines at baseline and after four weeks of rifaximin treatment (1200 mg/day). Intestinal permeability was indicated by serum soluble CD163 (sCD163), mannose receptor (sMR), and zonulin levels. To evaluate the gut microbiome, 16S ribosomal RNA gene sequencing was applied. Rifaximin ameliorated hyperammonemia and cognitive dysfunction, although it did not change the serum proinflammatory cytokine levels. It decreased EA levels as well as serum levels of sCD163 and sMR, but not zonulin, and both decreases in sCD163 and sMR showed positive correlations with EA decrease (ΔsCD163: Correlation coefficient (R) = 0.680, p = 0.023; ΔsMR: R = 0.613, p = 0.014, vs. ΔEA). Gut microbial analysis revealed that the richness and complexity of species were unchanged while the abundance of the Streptococcus genus was reduced after treatment with rifaximin. Collectively, rifaximin alleviated HE and endotoxemia with improved intestinal hyperpermeability in patients with decompensated cirrhosis, and this effect is partially involved in a gut microbial change.