Soluble CD163

CD163 is an endocytic receptor for haptoglobin-hemoglobin complexes and is expressed solely on macrophages and monocytes. As a result of ectodomain shedding, the extracellular portion of CD163 circulates in blood as a soluble protein (sCD163) at 0.7-3.9 mg/l in healthy individuals. The function of sCD163 is unknown, but during inflammation and macrophage activation, sCD163 levels increase acutely due to metalloproteinase-mediated cleavage near the cell membrane. It is now evident that sCD163 is very useful as a biomarker of macrophage activation in various inflammatory diseases, such as macrophage activation syndrome, sepsis, and liver disease. Moreover, sCD163 is a general risk marker of comorbidity and mortality in several chronic inflammatory disease states. Recently, sCD163 has been shown to be strongly associated with later development of type 2 diabetes in both lean and obese subjects, likely due to macrophage infiltration of adipose tissue and the liver. This review summarizes the current knowledge on the regulation of sCD163 in normal and pathological states and also deals with analytical aspects of sCD163 measurements in biological samples.     

Elevated soluble CD163 predicts renal function deterioration in lupus nephritis: a cohort study in Eastern China

ObjectiveThis study investigated the association between soluble scavenger receptor differentiation antigen 163 (sCD163) and the severity and prognosis of renal injury in lupus nephritis (LN).MethodsSerum sCD163 levels in 121 Eastern Chinese patients with LN who underwent renal biopsy were determined by enzyme-linked immunosorbent assays. Clinical data were collected, and the glomerular filtration rate and disease activity score of lupus were calculated. Pathological classification was performed, and renal pathological scores were assessed by the activity index (AI) and chronic index (CI). Kaplan–Meier survival curves were drawn to evaluate prognosis.ResultsThe pathological classification, AI and CI scores in the high sCD163 group were increased. The sCD163 levels were positively correlated with serum creatinine, blood urea nitrogen, AI scores and CI scores and negatively correlated with the estimated glomerular filtration rate. Kaplan–Meier survival analysis showed that the incidence of renal endpoint events was increased in the high sCD163 group compared with the normal sCD163 group.ConclusionThe serum sCD163 level correlates with the severity of LN and is an important indicator of poor renal prognosis in patients with LN.     

Macrophage activation marker soluble CD163 may predict disease progression in hepatocellular carcinoma

Background: Tumor associated macrophages are present in hepatocellular carcinoma (HCC) and associated with a poor prognosis. The aim of the present study was to investigate the levels and dynamics of soluble (s)CD163, a specific macrophage activation marker, in patients with HCC. Methods: In a cohort from Australia, we studied 109 HCC patients, 116 patients with chronic liver disease (CLD), and 52 healthy controls. We examined associations between baseline sCD163 and parameters of HCC severity as well as overall and progression-free survival. In a cohort of 42 Danish HCC patients, we measured sCD163 at baseline and 1, 4 and 12 weeks after ablative treatment. Results: In the Australian cohort, median sCD163 was similarly increased in HCC (5.6[interquartile range 3.5–8.0] mg/L) and CLD (6.1[3.6–9.6] mg/L) patients as compared to controls (2.0[1.5–2.7] mg/L, p?p?p?=?0.15). In the Danish cohort, patients with HCC progression at 12 weeks had an increase in sCD163. There was no association between sCD163 and HCC size, number, vascular invasion or metastasis in any of the cohorts. Conclusions: We confirmed increased sCD163 levels in CLD and HCC patients associated with Child-Pugh and MELD scores and portal hypertension, but not with HCC size and number, or metastasis. As a novel finding, baseline sCD163 appeared to predict a rapid HCC progression, as sCD163 increased during follow-up in HCC patients who showed progression.     

Adiponectin downregulates CD163 whose cellular and soluble forms are elevated in obesity

Background  CD163 is a monocyte/macrophage specific receptor whose soluble form (sCD163) is elevated in inflammatory diseases. Obesity is associated with chronic inflammation and low adiponectin, an anti-inflammatory adipokine. Adiponectin, 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR) and metformin activate the AMP-kinase that exerts anti-inflammatory effects, and the influence of adiponectin and these drugs on monocytic CD163 was analysed, and cellular and sCD163 were determined in obesity and type 2 diabetes.
Materials and methods  Monocytes were incubated with adiponectin, AICAR or metformin. Furthermore, monocytes and serum were obtained from type 2 diabetic patients (T2D), overweight (defined as a body mass index ≥ 25 kg m⁻²) and normal-weight (NW) controls. CD163 was analysed by immunoblot and sCD163 was measured by enzyme-linked immunosorbent assay in the supernatants of the monocytes and in serum.
Results  In monocytes, adiponectin reduced cellular and surface CD163, whereas sCD163 was not altered in the corresponding supernatants. Further, metformin and AICAR downregulated CD163. Monocytic CD163 was higher in T2D and obesity, whereas sCD163 in the supernatants was not elevated and neither correlated with serum sCD163 nor systemic adiponectin. There was a positive correlation of monocytic sCD163 with serum but not with monocytic IL-6. In the serum of obese controls and T2D patients, sCD163 was significantly higher compared to NW donors and was positively associated with systemic IL-6.
Conclusions  This study indicates that monocytic CD163 and systemic sCD163 are elevated in T2D and obesity. Adiponectin reduces CD163 in vitro , but additional factors related to obesity like IL-6 may be more relevant in vivo .     

Effects of lifestyle intervention on soluble CD163, a macrophage activation marker,in patients with non-alcoholic fatty liver disease

Objective: Liver macrophages play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Soluble CD163 (sCD163), a macrophage-specific biomarker, reflects disease activity in the range of liver diseases. The impact of lifestyle intervention on sCD163 in adult NAFLD patients has not been investigated.

Material and methods: We assessed 126 NAFLD patients participating in a lifestyle intervention study for sCD163 concentrations at baseline, after the three-month intervention period, and at long-term follow-up after 12 and 24?months.

Results: The median sCD163 concentration at baseline was 2.59?mg/L (IQR?=?1.78–3.63?mg/L). There was a significant decrease in sCD163 from baseline to three months follow-up (?0.64?mg/L, p?<?.001) with no difference between the four study groups (p?=?.6). At 12 and 24?months follow-up, the sCD163 concentrations had returned to baseline level (p?=?.3 and p?=?.1). Baseline sCD163 correlated with liver biomarkers and metabolic variables. There was a significantly greater decrease in sCD163 in patients who had a decrease in alanine aminotransferase (ALT) compared with patients with unchanged or increased ALT (?0.76?mg/L vs. ?0.41?mg/L, p?=?.02), and in patients with a decrease in HOMA-IR compared with individuals with no decrease (?0.86?mg/L vs. ?0.55?mg/L, p?=?.03).

Conclusion: sCD163 is associated with markers of liver necro-inflammation and glucose homoeostasis in NAFLD. Participation in a lifestyle intervention programme resulted in a significant reduction in sCD163. Our data support the utility of sCD163 as a biomarker for monitoring the efficacy of therapeutic interventions in NAFLD.     

系统性红斑狼疮患者血清sIL-2R、DNase1L3、sCD163水平变化及其联合检测意义

目的探系统性红斑狼疮患者血清可溶性白细胞介素2受体(sIL-2R)、脱氧核糖核酸酶Ⅰ样蛋白3(DNase1L3)、可溶性血红蛋白清道夫受体(sCD163)水平变化及其联合检测意义。方法回顾性选取2018年3月至2020年4月海南西部中心医院收治的系统性红斑狼疮患者123例。根据系统性红斑狼疮疾病活动度评分分为轻度组33例、中度组50例和重度组40例,同期健康体检者42例作为对照组。检测各组对象血清sIL-2R、DNase1L3、sCD163水平。评估sIL-2R、DNase1L3、sCD163联合检测系统性红斑狼疮价值。结果随着病情加重,sIL-2R和sCD163水平逐渐升高,DNase1L3水平逐渐降低,差异均有统计学意义(P <0.05);且轻度组、中度组、重度组sIL-2R和sCD163水平均高于对照组,DNase1L3水平低于对照组,差异均有统计学意义(P <0.05)。根据受试者工作特征(ROC)曲线获得,最佳界限以sIL-2R(146.51 U/mL)、DNase1L3(29.91 ng/m L)、sCD163(465.02 ng/m L)可获得ROC曲线下最大...     

Characterization of an enzyme-linked immunosorbent assay for soluble CD163

We have recently identified a soluble plasma form of CD163 sCD163, the macrophage receptor for clearance of haptoglobin-haemoglobin complexes, and we have observed highly elevated levels of sCD163 in subgroups of haematological patients. In the present study, we describe the optimization and characterization of a sandwich ELISA for the determination of the concentration of sCD163 in plasma and serum. The optimal concentrations of antibodies were determined systematically and the assay was calibrated by CD163 purified from human spleen membranes. The minimum detection limit was below 6.25 microg/L. Recovery of CD163 added to plasma samples was 106%. The concentration of sCD163 in paired serum and plasma samples correlated well (r2=0.99); however, serum levels were 1.1 times higher than the plasma levels. The addition of haptoglobin-haemoglobin complexes did not influence the assay. A very high stability of sCD163 was measured in whole blood and in plasma subjected to different temperatures and after repeated freezing and thawing.     

Macrophage serum markers in pneumococcal bacteremia: Prediction of survival by soluble CD163

OBJECTIVE: Soluble CD163 (sCD163) is a new macrophage-specific serum marker. This study investigated sCD163 and other markers of macrophage activation (neopterin, ferritin, transcobalamin, and soluble urokinase plasminogen activator receptor [suPAR]) as prognostic factors in patients with pneumococcal bacteremia. DESIGN: Observational cohort study. SETTING: Five university hospitals in Denmark. PATIENTS: A total of 133 patients with Streptococcus pneumoniae bacteremia (positive blood culture) and 133 age- and gender-matched controls. INTERVENTIONS: Samples were collected for biochemical analyses at the time of first positive blood culture. MEASUREMENTS AND MAIN RESULTS: sCD163 was highly correlated with other macrophage markers and was significantly elevated (median [25-75 percentiles], 4.6 mg/L [2.8-8.9]) compared with healthy controls (2.7 mg/L [2.1-3.3], p < .0001). Increased levels were observed in patients who needed intensive care (hemodialysis, p = .0011; hypotension, p = .0014; mechanical ventilation, p = .0019). Significantly lower levels of sCD163, ferritin, transcobalamin, and suPAR (but not C-reactive protein) were measured in patients > or =75 yrs. In patients <75 yrs, all macrophage markers were increased in patients who died from their infection compared with survivors, whereas no change was observed in any of the markers in the very old age. At cutoff levels of 9.5 mg/L (sCD163) and 1650 nmol/L (C-reactive protein), the relative risk for fatal outcome in patients <75 yrs was 10.1 (95% confidence interval 3.4-31.0) and 7.0 (95% confidence interval 2.4-21.6) for sCD163 and C-reactive protein, respectively. In a multivariate logistic regression model for patients <75 yrs, ferritin, transcobalamin, neopterin, and suPAR contained no significant information on the probability of survival when sCD163 and CRP were known (p = .25). CONCLUSIONS: Macrophage marker response in pneumococcal bacteremia was compromised in old age. In patients <75 yrs old, sCD163 was superior to other markers, including C-reactive protein, in predicting fatal disease outcome.     

Evaluation of a newly identified soluble CD14 subtype as a marker for sepsis

CD14, a high-affinity receptor for lipopolysaccharide (LPS), is a glycoprotein expressed on the surface membranes of monocytes/macrophages. We have identified a previously unknown form of soluble CD14, named soluble CD14 subtype (sCD14-ST), that is increased in patients with sepsis. To measure sCD14-ST concentrations in plasma, we prepared anti-sCD14-ST antibodies and developed an enzyme immunoassay (EIA) for this soluble form of CD14. With this assay, quantitative measurements are available within 4 h, and we compared the levels of sCD14-ST in plasma from normal subjects (healthy controls), patients with systemic inflammatory response syndrome (SIRS), and sepsis patients. The level of sCD14-ST in subjects with sepsis was much higher than the levels in subjects with SIRS and the healthy controls. Additionally, when a subject's sCD14-ST level was used as a diagnostic marker for sepsis, the area under the receiver operating characteristic (ROC) curve was 0.817, thereby demonstrating that elevated sCD14-ST levels were a better marker for sepsis than the other molecular markers we tested. sCD14-ST levels also correlated with procalcitonin (PCT) levels and with sequential organ failure assessment (SOFA) scores. Finally, changes in sCD14-ST concentration correlated with the severity of sepsis. Taken together, these results indicate that sCD14-ST is a useful marker for the rapid diagnosis of sepsis and for monitoring the severity of the disease.     

Human monocyte CD163 expression inversely correlates with soluble CD163 plasma levels

BACKGROUND: CD163 is a monocyte/macrophage-restricted receptor involved in the clearance of hemoglobin-haptoglobin complexes and regulation of inflammatory processes. CD163 is shed from the cell surface and exists as a soluble form in plasma (sCD163). Monocyte CD163 and sCD163 are potential diagnostic tools in variety of disease states. METHODS: We determined the relation between plasma sCD163 levels by enzyme-linked immunosorbent assay, membrane expressions of CD163, CD64, and CD14 on blood monocytes by flow cytometry, and monocyte counts in 129 random blood samples. RESULTS: A strong inverse correlation was found between membrane CD163 expression and sCD163 levels (r = -0.65, P < 0.001). Monocyte CD163 expression and SCD163 levels did not correlate with the monocyte absolute count. CONCLUSIONS: The inverse relation between monocyte surface CD163 expression and sCD163 levels in human blood suggests that plasma sCD163 is derived from circulating monocytes, in addition to an unknown component from tissue macrophages. The lack of correlation with the absolute monocyte number suggests that such a balance is driven by the functional state of monocytes, rather than simply by numerical changes in circulating cells. We propose that further clinical evaluations of CD163 as a diagnostic parameter should include simultaneous measurements of soluble and cell-bound forms of this antigen.     

病毒性肝炎患者血清中可溶性CD30检测的临床意义

目的检测病毒性肝炎患者血清中可溶性CD30（sCD30）的水平及其与血清丙氨酸氨基转移酶（ALT）的相关性及临床意义。方法采用酶联免疫吸附试验（ELISA）检测85例病毒性肝炎患者（包括43例乙型肝炎、19例丙型肝炎、23例戊型肝炎）血清中sCD30的水平,同时采用日立7600生化仪检测血清中ALT的水平。另取30例ALT正常的乙型肝炎病毒（HBV）携带者作为乙型肝炎对照,30名健康体检者作为正常对照。结果各型病毒性肝炎患者血清中sCD30和ALT水平均明显高于正常对照,ALT水平升高的乙型肝炎患者较ALT正常的HBV携带者血清中sCD30水平明显升高。各型病毒性肝炎患者血清中sCD30水平均与ALT呈正相关。结论病毒性肝炎存在Th2型细胞的活化,血清sCD30水平可以作为肝炎活动性的检测指标。     

The diagnostic value of soluble CD163 in patients presenting with chest pain

BackgroundCD163 is a scavenger receptor for the uptake of haptoglobin–hemoglobin (Hpt–Hb) complexes. The Hpt–Hb complexes are being formed in the plaque in response to intraplaque hemorrhage, a hallmark of atherosclerotic plaque instability. We therefore investigated whether soluble CD163 (sCD163) was elevated in patients with an acute coronary syndrome.MethodsAll subjects presenting with chest pain suggestive of myocardial ischemia referred to either the emergency department or the coronary care unit were included in a prospective follow-up study. Plasma was collected and frozen at ? 80 °C until assayed. sCD163 was measured using a commercially available Elisa assay.ResultsOf 526 included chest pain patients, the final diagnosis was non-cardiac chest pain in 244 (46%) patients, non-STEMI in 67 (13%), and STEMI in 215 (41%). The non-STEMI patients were older, used more medication, had undergone more often coronary interventions, but did not differ with respect to risk factors, except for a higher incidence in dyslipidemia. Unexpectedly, sCD163 did not differentiate between patients with non-STEMI or STEMI and the non-cardiac chest pain patients (2.09 ± 0.76 versus 2.24 ± 0.86).ConclusionAlthough ACS is characterized by intraplaque hemorrhage, the amount of intraplaque Hb release seems not to be substantial enough to result in a measurable difference in sCD163.     

The expansion of CD14+ CD163+ subpopulation of monocytes and myeloid cells‐associated cytokine imbalance; candidate diagnostic biomarkers for celiac disease (CD)

Celiac disease (CD) is a chronic autoimmune disorder of small intestine against dietary gluten, among genetically predisposed individuals. Monocytes are versatile innate immune cells involved in the regulation of inflammation, and strongly involved in the intestinal immunity. However, the role of monocytes and their subtypes in CD is not well demonstrated.MethodsHere, we assessed the polarization of CD14+ monocytes by evaluating the M1 (CD16) and M2 (CD163) markers by flowcytometry, their soluble forms (sCD16 and sCD163), and the serum levels of IL‐10, IL‐12, TGF‐β, and TNF‐α cytokines using ELISA method, among 30 CD patients and 30 sex‐ and age‐matched healthy subjects (HS). We also analyzed the diagnostic values of all variables with significant differences.ResultsCD14+CD163+ monocytes were more frequent in CD patients than HS, while CD14+CD16+ monocytes were higher in HS. IL‐10and TNF‐α increased, and TGF‐β expression was decreased among CD patients. The sCD16 serum levels were elevated in patients, while sCD163 was higher but not significant among CD patients. CD163+/CD16+ and IL‐10/IL‐12 ratios were higher in CD patients, and TGFβ/TNFα ratio was higher in HS group. IL‐10, CD14+CD163+, TNF‐α, and IL‐10/IL‐12 ratios with the AUC over 0.7 were introduced as fair diagnostic markers. Our findings revealed that the M2 (CD14+CD163+) monocytes were more frequent among CD patients, and the cytokine balance was disturbed.ConclusionAccording to the significant functional diversities of monocyte subtypes between CD patients and HS group, these immunologic markers could be introduced as specific diagnostic biomarkers for CD.     

The Levels of Soluble CD40 Ligand and C-Reactive Protein in Normal Weight,Overweight and Obese People

Objective: Obesity has been suggested as an independent risk factor for cardiovascular disease. Increasing evidence shows that engagement of soluble CD40 ligand (sCD40L) with its receptor plays a crucial role in the pathogenesis of atherosclerosis. The aim of the present study was to test whether obesity is associated with low-grade systemic inflammation as measured by serum high-sensitive C-reactive protein (hsCRP) and sCD40L concentration.Methods: Serum hsCRP and sCD40L concentrations were measured in 148 nondiabetic people. The participants were divided into three groups depending upon their body mass index (BMI) levels: Group 1 (normal weight), BMI<25 kg/m²; Group 2 (overweight), BMI 25 kg/m² to 29.9 kg/m²; and Group 3 (obese), BMI≥30 kg/m².Results: Obese people had more elevated hsCRP levels than both their normal weight and overweight counterparts (P=0.000 and P=0.000, respectively). Similarly, serum concentrations of sCD40L were significantly higher, statistically, in obese subjects compared with normal weight subjects (P=0.003). In addition, obese subjects had higher values of sCD40L than overweight subjects, but the difference did not reach statistical significance (P=0.063). The levels of high-density lipoprotein cholesterol were significantly lower in obese subjects compared to normal weight subjects (P=0.048). The analysis of platelet count disclosed a statistically significant difference between obese subjects and normal weight subjects (P=0.028). The levels of BMI were positively correlated with the serum levels of hsCRP and sCD40L in all subjects (r=0.514, P=0.000 and r=0.283, P=0.000, respectively). Levels of hsCRP were positively correlated with waist circumference, fasting glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, leukocytes, platelets, systolic and diastolic blood pressure. Similarly, soluble CD40L levels were positively correlated with waist circumference, fasting glucose and leukocytes.Conclusion: Obese patients showed a significant increase of hsCRP and sCD40L levels compared with normal weight subjects, which might contribute to the known proinflammatory milieu found in these patients.     

Evaluation of serum cystatin C and chromogranin A as markers of nephropathy in patients with Type 2 diabetes mellitus

Abstract

The chronic joint inflammation in axial spondyloarthritis (axSpA) is characterized by infiltration of activated macrophages. The haptoglobin–hemoglobin receptor CD163 and the mannose receptor CD206 are strongly expressed on M2c and M2a macrophages, respectively. We measured the soluble forms of the receptors (sCD163 and sCD206) in plasma (PL) in two axSpA cohorts. All patients fulfil the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axSpA and/or the 1984 modified New York criteria for ankylosing spondylitis. The first cohort included anti-TNF-α treated patients with active axSpA (n?=?30); the second cohort included patients in early disease stages (n?=?38). Plasma sCD163 and sCD206 were both within the reference interval of healthy controls (HC), but sCD163 decreased slightly during anti-TNF-α treatment [baseline: 1.49?mg/L (IQR: 1.22–1.77?mg/L, 12?weeks: 1.29 (IQR: 1.09–1.57) mg/L, 20?weeks: 1.25 (IQR: 0.99–1.75) mg/L, 52?weeks: 1.39 (IQR: 1.15–1.78) mg/L], while sCD206 increased [baseline: 0.17 (IQR: 0.13–0.21) mg/L, 12?weeks: 0.19 (0.16–0.23) mg/L, 20?weeks: 0.20 (0.14–0.24) mg/L, 52: 0.19 (IQR: 0.14–0.23) mg/L], pointing toward a shift in polarization of involved macrophages. Plasma levels of sCD206 proved significantly higher in patients with early disease stages and definite radiological sacroiliitis (n?=?10). This was not the case for sCD163. A significant increase in response to anti-TNF-α treatment, could suggest sCD206 as a marker of response to anti-TNF-α treatment, however, the potential for the two macrophage markers as diagnostic and prognostic indicators of disease in axSpA is weak.     

肝硬化患者血清内毒素调节蛋白水平及其临床意义

目的：探讨检测伴肠源性内毒素血症的肝硬化患者血中内毒素结合蛋白(LBP)、杀菌性／通透性增加蛋白(BPI)及可溶性sCD14水平的临床意义。方法：应用基质显色法和ELISA双抗体夹心法，检测45例肝硬化患者血中内毒素脂多糖(LPS)、LBP、BPI和sCD14水平，并以15例健康献血员作为对照。结果：肝功能为A级、B级和C级的肝蘸化患者其血中LPS、LBP、BPI和sCD14水平均明显高于献血员；肝硬化死亡息者的LPS、LBP、BPI和sCD14水平显著高于存活者。结论：肝硬化患者伴肠源性内毒素血症时，血清LBP和sCD14水平升高和BPI相对不足，可显著提高机体对LPS的敏感性。     

Soluble CD30 serum levels before and after treatment with alpha-interferon in patients with chronic hepatitis C.

It has been suggested that soluble CD30 (sCD30) serum levels in chronic hepatitis C are correlated with the activity of the disease and with the outcome of interferon (IFN) treatment. In this study, sCD30 serum levels in 25 patients with chronic hepatitis C, before and after treatment with IFN-2alpha, were measured. A total of 20 healthy subjects were used as controls. High sCD30 levels in serum were found in 36% of patients and in 5% of controls. In patients with sCD30 levels above or within the normal range, no significant differences in age, gender, serum transaminases and histology activity index were found. In relation to IFN treatment, only responder patients had serum sCD30 higher than controls, although the difference between responders and non-responders was not significant. No changes from baseline values were observed after treatment. Although high, sCD30 serum levels in chronic hepatitis C are not correlated with the disease activity, are not affected by IFN treatment and are not predictors of response to IFN treatment.     

系统性红斑狼疮患者sCD40L水平变化及临床意义

目的对系统性红斑狼疮（SLE）患者血清中可溶性CD40配体（sCD40L）的含量变化及临床意义进行讨论。同时分析血小板减少组SLE患者与血小板正常组SLE患者血清中sCD40L的含量差别。初步探讨血清和血浆中sCD40L浓度有无差异。分析SLE患者血清中sCD40L的含量与系统性红斑狼疮疾病活动度评分（SLEDAI评分）有无相关性。方法用酶联免疫吸附法检测25例SLE患者和15例正常人血清中及18例正常人血浆中sCD40L的浓度。结果①血小板正常组SLE患者血清中的sCD40L浓度明显高于正常对照组和血小板减少组SLE患者。②SLE患者血清sCD40L浓度、血小板正常组SLE患者血清中sCD40L浓度、血小板减少组SLE患者血清中sCD40L浓度与SLEDAI评分均无相关性。③SLE患者血清中sCD40L浓度与血小板计数呈正相关。④发现正常人血清中sCD40L的浓度明显高于血浆中的sCD40L的浓度。结论 SLE患者血清中sCD40L浓度较正常人高可能参与SLE的发生发展过程。血小板计数对血清中sCD40L浓度有一定程度的影响,且SLE患者血清中sCD40L与SLEDAI评分无相关性,在临床上sCD40L不适合作为监测SLE疾病的活动度的指标。     

Association of low-grade inflammation and platelet activation in patients with hypertension with microalbuminuria

Increased levels of sCD40L (soluble CD40 ligand) have been associated with enhanced in vivo platelet activation, and may represent a molecular link between inflammation and a prothrombotic state. The aim of the present study was to analyse the relationship between platelet activation, endothelial dysfunction, low-grade inflammation and sCD40L in patients with hypertension with or without MA (microalbuminuria). A cross-sectional comparison of sCD40L levels was performed in 25 patients with MH (essential hypertension with MA) pair-matched for gender and age with 25 patients with EH (essential hypertension) and 25 HS (healthy subjects with normotension). Circulating levels of CRP (C-reactive protein), a marker of inflammation, sP-selectin (soluble P-selectin), a marker of in vivo platelet activation, and ADMA (asymmetric dimethylarginine) and vWF (von Willebrand factor), markers of endothelial dysfunction, were analysed in each subject. sCD40L levels were increased in patients with MH compared with either patients with EH (P<0.001) or HS (P<0.0001). A highly significant correlation between plasma sCD40L and sP-selectin (P<0.0001), vWF (P<0.001) or CRP levels (P<0.05) was observed in patients with MH. Multivariate regression analysis showed that sP-selectin was the strongest independent predictor of sCD40L levels (P<0.0001) in patients with MH. Patients with hypertension with both vWF and CRP levels above the median had the highest sCD40L levels (P<0.0001). Factorial ANOVA of all of the patients with hypertension confirmed that only patients with MH with low-grade inflammation had elevated levels of sCD40L. In conclusion, sCD40L levels appear to discriminate a subset of patients characterized by MA and low-grade inflammation, suggesting that inhibition of the CD40/CD40L system may represent a potential therapeutic target in subjects with hypertension at a high risk of cardiovascular events.     

肺癌患者血浆CD62P、血清sCD40/sCD40L水平的检测及临床意义

目的：通过测定肺癌患者血清中可溶性CD40（sCD40）、可溶性CD40L（sCD40L）、血浆CD62P的含量,探讨血小板源性CD40/CD40L在肺癌外周血中的表达及其临床意义。方法体外分离85例肺癌患者（肺癌组）和25名健康志愿者（对照组）的血清和血浆。用酶联免疫吸附试验（ELISA）法对血清sCD40、sCD40L、血浆CD62P的含量进行测定。结果（1）肺癌组血清sCD40、sCD40L、血浆CD62P含量明显高于健康对照组（P均＜0.01）。（2）不同病理类型肺癌患者血清sCD40、sCD40L含量、血浆CD62P含量差异均无统计学意义（P均＞0.05）。（3）肺癌患者sCD40、sCD40L、CD62P的含量随临床分期的进展而呈升高趋势。（4）有远处转移肺癌患者sCD40、sCD40L、CD62P的含量明显高于无远处转移患者（P均＜0.05）。（5）肺癌患者术后2周时血浆CD62P、血清sCD40L的含量均较术前下降,但血清sCD40含量与术前相比差异无统计学意义。且其CD62P、sCD40L的表达水平成正相关关系（r=0.300,P＜0.05）。结论（1）肺癌患者血清sCD40、sCD40L、血浆CD62P含量增加,且表达水平与肺癌的进展程度相关,血小板源性CD40/CD40L系统在肺癌的发病中具有重要作用。（2）检测血小板源性CD40L、CD62P表达水平对研究肺癌的临床分期、预后判断有一定的参考价值。