Enhanced plasma soluble CD40 ligand levels in essential hypertensive patients with blunted nocturnal blood pressure decrease

BACKGROUND: Hypertensives with a blunted nocturnal blood pressure (BP) decrease have increased risk of developing atherosclerotic disease. Soluble CD40 ligand (sCD40L) is involved in the pathogenesis of risk factor-related vascular damage. Therefore, we evaluated the relationship between circulating sCD40L levels, circadian BP profile, and early carotid atherosclerosis in essential hypertensives. METHODS: Plasma sCD40L concentrations were assessed in two groups of 25 never-treated hypertensives, without additional cardiovascular risk factors, differentiated on the basis of a nocturnal decrease of BP either of >10% (dippers) or <10% (nondippers) of daytime values, and in 25 matched normotensives. Carotid intima-media thickness (IMT) was also measured in all participants. RESULTS: Plasma sCD40L concentrations were higher in nondippers (4.9 +/- 1.2 ng/mL) than in dippers (3.7 +/- 0.7, P = .0005) and controls (1.6 +/- 0.6, P < .0001). These latter had lower sCD40L concentrations than dippers (P < .0001). The IMT was higher in both hypertensive groups than in normotensives (P < .0001). In the entire hypertensive population IMT directly correlated with circulating levels of sCD40L (r = 0.365, P = .01) and inversely correlated with nocturnal systolic BP decreases (r = -0.286, P = .043). In a multivariate regression analysis sCD40L was the main determinant of IMT (r(2) = 0.157, P = .004). CONCLUSIONS: Nondippers have enhanced plasma sCD40L levels, which may contribute to their increased susceptibility to develop vascular damage.     

阿托伐他汀钙片对心绞痛患者血清可溶性CD40配体与C反应蛋白的干预研究

目的 探讨阿托伐他汀钙片对心绞痛患者血清可溶性CD40配体(CD40L)与高敏C反应蛋白(hs-CRP)的干预作用.方法 65例冠心病患者,其中稳定型心绞痛患者30例(SA组),不稳定型心绞痛患者35例(UA组),所有患者于入院当天清晨、治疗后2、4、6周静脉血,测定血清hsCRP、血清可溶性CD40L水平,并对两组结果进行比较.结果 治疗前UA组血清可溶性CD40L、hs-CRP浓度分别为(20.52±2.91)μg/L、(7.96±1.69) mg/L,明显高于SA组(7.96±1.35)μg/L、(1.58±0.91) mg/L(t=21.705、18.493,均P＜0.05),而两组治疗后血清可溶性CD40L、hs-CRP浓度均较治疗前明显降低(均P＜0.01).结论 血清可溶性CD40L、hs-CRP参与了不稳定型心绞痛的病理生理过程,可以作为反映易损斑块的指标,阿托伐他汀钙片可通过降低血清可溶性CD40L、hs-CRP而加强粥样硬化斑块的稳定性.     

Enhanced soluble CD40L in patients with the metabolic syndrome: relationship with in vivo thrombin generation

Aims/hypothesis The metabolic syndrome is associated with proinflammatory and prothrombotic states. This study was designed to assess the behaviour of soluble CD40 ligand (sCD40L) and prothrombin fragment F ₁₊₂, a marker of thrombin generation, in patients with the metabolic syndrome.Methods We investigated 106 patients with the metabolic syndrome, diagnosed according to the ATPIII report, and 104 subjects without the metabolic syndrome.Results Plasma values of sCD40L and F ₁₊₂ were higher in patients with the metabolic syndrome (4.11±1.64 vs 2.61±0.89 ng/ml and 1.54±0.49 vs 0.87±0.21 nmol/l, respectively; p<0.001) and were significantly correlated (r=0.925, p<0.001). Stepwise multiple linear regression analysis showed that sCD40L was significantly associated with F ₁₊₂, female sex and waist circumference.Conclusions/interpretation Patients with the metabolic syndrome have enhanced values of plasma sCD40L and F ₁₊₂. The study provides further insight into the relationship between metabolic syndrome, inflammation and thrombosis.     

Elevated circulating soluble form of CD40 ligand in patients with cardiac syndrome X

ObjectivesMarkers of non-specific inflammation, such as C-reactive protein (CRP) or leukocyte count are increased in end-stage renal disease patients. Recent studies have shown positive associations between inflammatory markers and cardiovascular mortality in kidney transplant recipients, but these analyses had been limited by sample size. The aim of our study was to determine the association between pretransplant CRP levels and leukocyte counts with posttransplant outcome in a prospectively enrolled cohort of kidney transplant recipients.Methods459 consecutive patients transplanted from July 1995 to December 2007 were analyzed. Both markers were obtained prior to transplantation and patients were grouped according to baseline CRP levels (<5 mg/l or ≥5 mg/l) or leukocyte counts (<10,000/μl or ≥10,000/μl).ResultsMajor cardiac events were associated with elevated pretransplant CRP levels (p < 0.00003) but not leukocyte counts. Furthermore, more acute rejection episodes within 4 weeks or 6 months, as well as a lower probability of survival at 6 months were found in patients with elevated pretransplant CRP levels or leukocyte counts.ConclusionElevated pretransplant serum CRP level is a risk predictor for major cardiac events in renal transplant patients. It is also predictive, besides leukocyte counts, for acute rejection episodes. Elevated CRP levels and initial high leukocyte counts may prove to be useful markers for posttransplant course and warrant the close follow-up of such patients.     

Inverse correlation between soluble CD40 ligand and soluble CD40 is absent in patients with unstable angina

The CD40/CD40 ligand (CD40L) system mediates inflammatory processes important in atherogenesis and plaque instability. The expression of CD40L on activated T cells was suppressed by soluble CD40 (sCD40) in vitro. However, the relationship between soluble CD40L (sCD40L) and sCD40 in unstable angina (UA) is still unknown. Thirty-seven consecutive patients with recent chest pain or discomfort were recruited. Patients with both Braunwald's class IB–IIIB and with coronary stenosis (or stenoses) of >75% were assigned to the UA group (n = 19, aged 67.2 ± 8.2 years), and the rest to the control group (n = 18, aged 63.4 ± 8.7 years). The serum levels of sCD40L and sCD40, and the plasma levels of matrix metalloproteinase (MMP)-9, were measured by enzyme-linked immunosorbent assays. A significantly inverse correlation between sCD40L and sCD40 was shown in the controls (r = −0.72, P = 0.0007), but was absent in the UA group (r = −0.16, P not significant), although there was no statistical significance between these groups in terms of serum levels of sCD40L or sCD40. The difference of the regression slopes of these regression lines was statistically significant (P < 0.01). Additionally, there was a significant correlation between sCD40 and plasma levels of MMP-9 in the patients with and without UA (r = 0.58, P = 0.0096), but no significant correlation between sCD40L and MMP-9 levels (r = 0.00, P not significant). The balance between CD40 and CD40L may be lost in patients with UA. Soluble CD40 expression may also be related to MMP-9 expression in atherosclerotic tissues.     

Serial changes in circulating concentrations of soluble CD40 ligand and C-reactive protein in patients with unstable angina undergoing coronary stenting.

BACKGROUND: This study tested the hypothesis that serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L) significantly reflect serial changes in patients with unstable angina, and thus the serum concentrations of these inflammatory biomarkers may be good candidates for predicting late restenosis after coronary stenting. METHODS AND RESULTS: The circulating concentrations of sCD40L and hs-CRP were prospectively measured (both pre-procedure, and on days 21, 90, and 180 after the procedure) in 77 consecutive patients with unstable angina undergoing coronary stenting. These inflammatory mediators were also evaluated in 30 healthy volunteers. The serum concentrations of sCD40L and hs-CRP were significantly higher pre-procedure in study patients than in normal control subjects (all p values < 0.0001). These inflammatory markers then declined to a substantially lower concentration by day 21 (all p values < 0.05). Circulating concentrations of hs-CRP in each patient then differed little from each other afterwards. However, the sCD40L concentration was once again raised significantly on days 90 and 180 as compared to day 21 (both p values < 0.05). This study found no significant link between raised circulating concentrations of sCD40L and hs-CRP and late restenosis. CONCLUSIONS: Circulating concentrations of sCD40L and hs-CRP were significantly increased in unstable angina patients pre-procedure and declined substantially thereafter. However, the circulating concentrations of these 2 inflammatory mediators were not useful in predicting late restenosis following coronary stenting.     

Abnormal soluble CD40 ligand and C-reactive protein concentrations in hypertension: relationship to indices of angiogenesis

BACKGROUND: Abnormal inflammation, platelets and angiogenesis are involved in the pathophysiology of cardiovascular disease (CVD). OBJECTIVE: To test the hypothesis that concentrations of high sensitive C-reactive protein (CRP, an index of inflammation) and soluble CD40 ligand (sCD40L, an index of platelet activation) would be abnormal in hypertension, and in turn, be related to plasma indices of angiogenesis, the angiopoietins-1 and -2, and vascular endothelial growth factor (VEGF), in addition to the presence or absence of CVD. METHODS: Using a cross-sectional approach, we measured plasma concentrations of CRP, sCD40L, VEGF, and angiopoietins-1 and -2 in 147 patients with hypertension (85 with a history of CVD event/s, 62 CVD event-free) and 68 age- and sex-matched healthy controls. RESULTS: Concentrations of sCD40L (P = 0.039), CRP (P < 0.001), angiopoietin-1 (P < 0.001), angiopoietin-2 (P = 0.003) and VEGF (P < 0.001) were all greater amongst hypertensive patients than in controls. There were no significant differences in sCD40L and VEGF concentrations between hypertensive individuals with and without CVD events, but CRP and angiopoietin-1 concentrations were significantly greater amongst those with CVD events. On multiple regression analysis, sCD40L was associated with angiopoietin-2 (P = 0.01) and VEGF (P = 0.007) in hypertensive individuals, but no such associations were found within the healthy control group. CONCLUSION: In patients with hypertension, sCD40L was associated with increased circulating markers of abnormal angiogenesis (angiopoietin-2, VEGF). The interaction between sCD40L and angiogenesis may contribute to the pathophysiology of CVD in hypertension.     

Soluble CD40 ligand levels in patients with hypertension

CD40 ligand interaction with its receptor (CD40) not only mediates lymphocyte communication, but also associates with chronic inflammation and atherothrombosis. High soluble CD40L (sCD40L) levels were reported in dyslipidemia, diabetes mellitus, and coronary disease. So far, there are no data about sCD40L levels in hypertension. We investigated sCD40L and high sensitive C reactive protein (hsCRP) levels in 30 nonobese young hypertensive men and 30 matched controls. sCD40L and hsCRP levels were not different, and there were no correlations between blood pressure and sCD40L or hsCRP levels. These results might indicate lack of any inflammatory state in new onset hypertension.     

High-sensitivity C-reactive protein in patients with metabolic syndrome

High-sensitivity C-reactive protein (CRP) has been shown to predict cardiovascular disease. Metabolic syndrome has been found to play a critical role in the development of cardiovascular disease. The purpose of this report is to assess the relationship between CRP and the metabolic syndrome. A total of 50 patients with metabolic syndrome and 40 healthy persons were included in the study. Plasma concentrations of CRP were measured by means of particle-enhanced immunonephelometry with the Behring nephelometer using N Latex CRP mono reagent. CRP levels were higher in patients with metabolic syndrome than control group (10.6 +/-5.4 mg/L vs 3.5 +/-0.8 mg/L, p<0.001). In partial correlation, plasma CRP positively correlated with body mass index (p<0.001), waist circumference (p<0.001), waist-to-hip ratio (p<0.01), total cholesterol (p<0.001), LDL-cholesterol (p=0.033), triglyceride (p=0.023), and fasting blood glucose (p=0.043) in patients with metabolic syndrome. HDL-cholesterol did not significantly correlate with CRP (p>0.05). In multiple regression analysis, body mass index (p<0.01), waist circumference (p<0.01), and fasting blood glucose (p<0.01) showed independent correlations with plasma CRP. CRP levels were found higher in patients with metabolic syndrome. These results suggest that abdominal obesity is the critical correlates of elevated plasma CRP levels found in patients with metabolic syndrome. These patients carrying high risk for cardiovascular events must be followed closely.     

Enhanced levels of CD154 (CD40 ligand) on platelets in patients with chronic heart failure

BACKGROUND: Inflammation plays a significant contributory role in the pathogenesis of chronic heart failure (CHF). Previous data have shown enhanced plasma levels of proinflammatory cytokines, i.e. TNF-alpha and IL-6, as well as a persistent immune activation in patients with CHF. Furthermore, the immune modulator CD154 has been receiving increased attention, since it plays a key role in the pathophysiology of multicellular vascular events such as thrombosis, inflammation and atherosclerosis. Since CD154 initiates and maintains the release of proinflammatory cytokines from endothelial cells, its potential role for the development and progression of CHF is of interest. METHODS: Fifty patients with CHF (aged 66.9+/-12.6 years, mean ejection fraction 22.1+/-9.2%, NYHA II-IV, 39 of ischemic origin, 11 with idiopathic dilated cardiomyopathy) and 15 healthy controls (aged 62.5+/-9.8 years) were examined. Thirty-two patients were taking aspirin (100 mg/day). Blood was drawn from a peripheral vein and immediately fixed with 1% paraformaldehyde, incubated with anti-CD154, anti-P-selectin, and anti-CD61 and thereafter analyzed by flow cytometry. RESULTS: Patients with CHF showed significantly enhanced expression of platelet-bound CD154 and P-selectin as compared to controls (CD154: median 35.6 25th percentile: 26.3; 75th percentile: 44.6 vs. 12.8; 25th: 6.8; 75th: 15.6 mean fluorescence intensity [MFI], P<0.001; P-selectin: median 3.2 25th percentile: 1.9; 75th percentile: 5.9 vs. 1.4; 25th: 1.2; 75th: 1.9, MFI, P<0.001). CD154 expression on platelets positively correlated with increasing NYHA-class. In contrast, no significant differences in serum levels of soluble CD154 or CD40 expression on monocytes were detected in the study groups. Antiplatelet-therapy with aspirin did not influence CD154 or P-selectin expression on platelets. CONCLUSION: Our pilot study demonstrates significantly enhanced levels of CD154 on platelets in patients with CHF. This suggests that the CD40-CD154 axis may contribute to the proinflammatory milieu, which exists in CHF and thus may play a pathogenic role in the development and progression of CHF.     

Diverse associations of microalbuminuria with C-reactive protein, interleukin-18 and soluble CD 40 ligand in male essential hypertensive subjects

BACKGROUND: Microalbuminuria (MA) and low-grade inflammation constitute emerging markers of subclinical atherosclerosis. We investigated whether urinary albumin excretion, expressed as the albumin-to-creatinine ratio (ACR), is associated with high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-18, and soluble CD40 ligand (sCD40L), in hypertensive subjects. METHODS: The study population consisted of 108 nondiabetic male patients with newly diagnosed untreated stage I to II essential hypertension (aged 44.6 years, office blood pressure [BP] 148/95 mm Hg). According to ACR values determined as the average of two nonconsecutive overnight spot urine samples, subjects were divided into microalbuminurics (n = 28) (mean ACR = 30 to 300 mg/g) and normoalbuminurics (n = 80) (mean ACR <30 mg/g). RESULTS: Although microalbuminurics as compared to normoalbuminuric hypertensives had greater hs-CRP levels (2.55 +/- 1.18 v 1.45 +/- 0.52 mg/L, P < .0001), independently of confounding factors, these two groups did not differ regarding IL-18 and sCD40L values (P = not significant [NS] for both cases). In the entire population, ACR exhibited a positive correlation with hs-CRP (r = 0.623, P < .0001), whereas there was no association with both IL-18 and sCD40L (P = NS for both cases). When multiple linear regression analysis was performed, it was revealed that age, body mass index, office systolic BP, total cholesterol, and hs-CRP levels were significant independent predictors of the ACR (P < .05). CONCLUSIONS: In essential hypertensive subjects, MA is accompanied by elevated hs-CRP levels, but not by augmented IL-18 and sCD40L concentrations, suggesting activation of different inflammatory pathways in the progression of renal and cardiovascular atherosclerotic disease. The pathophysiologic mechanisms of these associations remain to be further elucidated in future studies.     

Coronary artery disease progression is associated with C-reactive protein and conventional risk factors but not soluble CD40 ligand

BACKGROUND: Coronary artery disease (CAD) is a major cause of death worldwide. Epidemiological studies have documented conventional risk factors; however, no studies to date have addressed the roles of soluble CD40 ligand (sCD40L) and monocyte chemoattractant protein-1 (MCP-1), and there have been few reports on other novel risk factors in CAD progression. The aim of the present study was to explore the roles of novel and conventional risk factors in CAD progression. METHODS: Patients with stable angina pectoris who underwent repeat coronary angiograms and had serum samples at the time of their first catheterization between March 1999 and January 2004 were enrolled. Those who had progression of coronary atherosclerosis were classified into the progression group (n = 66). Those who did not have CAD progression were classified into the nonprogression group (n = 124). RESULTS: There were more cases of diabetes mellitus (36% versus 20%; P = 0.024) and more men (92% versus 81%; P = 0.040) in the CAD progression group than in the nonprogression group, respectively. The progression group also had poorer lipid profiles than the nonprogression group, including higher total cholesterol (188+/-42 mg/dL versus 173+/-39 mg/dL, respectively; P = 0.014) and low density lipoprotein cholesterol (122+/-38 mg/dL versus 112+/-36 mg/dL, respectively; P = 0.025). In terms of inflammatory markers, progression patients had higher baseline high-sensitivity C-reactive protein (hs-CRP) concentrations (P = 0.018), which was also related to the subsequent angiographic severity score changes; however, sCD40L (6182+/-4352 pg/mL versus 6244+/-4602 pg/mL; P = 0.961), MCP-1 (427+/-540 pg/mL versus 341+/-128 pg/mL; P = 0.580) and adhesion molecules concentrations were indifferent between the progression group and the nonprogression group, respectively. Using a multivariate logistical regression model, the ORs for predicting progression were 2.19 for diabetes mellitus, 2.04 for hypercholesterolemia and 1.52 for hs-CRP (P < 0.05). CONCLUSION: In the present study, only conventional risk factors, and particularly hs-CRP, were markers for predicting CAD progression. Novel risk factors, such as concentrations of sCD40L, MCP-1 and adhesion molecules, did not play significant roles.     

Exercise training decreases plasma levels of soluble CD40 ligand and P-selectin in patients with chronic heart failure

BACKGROUND: Inflammation may contribute to the pathogenesis of chronic heart failure. Some reports suggesting that exercise training may have net anti-inflammatory effects in heart failure patients exists, although the results are somewhat conflicting. METHODS: Fifteen patients with mild to moderate chronic heart failure underwent an exercise training program of 20 weeks. They were examined at baseline, at the end of the training period, and 1 year after end of training. RESULTS: Our main findings were as follows: (i) during the training period there was a significant increase in exercise capacity as estimated by the 6-min walk test as well as an improvement in several quality of life parameters, (ii) these changes were accompanied by a marked decrease in plasma levels of soluble CD40 ligand and P-selectin, probably reflecting an attenuated platelet-mediated inflammation, (iii) in contrast, there were no changes in plasma levels of tumor necrosis factor alpha, monocyte chemoattractant protein-1, or vascular cellular adhesion molecule-1 during the training period, (iv) except for an increase in systolic annular velocity there were no changes in echocardiographic variables during the training period, (v) one year after the training, in a period without systematic training, plasma levels of soluble CD40 ligand, and P-selectin had returned to baseline levels along with a nonsignificant reduction in 6-min walk test. CONCLUSION: Our findings suggest a potent downregulatory effect of exercise training on platelet-mediated inflammation in patients with chronic heart failure. Further studies are needed to clarify the clinical significance of these findings.     

炎性因子与急性冠状动脉综合征相关性研究

目的探讨可溶性CD40配体（sCD40L）、髓过氧化物酶（MPO）和高敏C反应蛋白（hs—CRP）等炎性指标与冠心病冠状动脉狭窄程度及病情严重度间的相关性。方法冠状动脉造影患者85例，按狭窄程度分无狭窄组、轻度狭窄组、中度狭窄组和重度狭窄组；按病情分为急性心梗（AMI）、不稳定型心绞痛（UAP）、稳定型心绞痛（SAP）和健康对照组。结果①血清sCD40L水平，AMI组[（16．42±4．66）ng／m1]与UAP组[（13．50±5．29）ng／m1]显著高于SAP组[（9．22±3．65）ng／m1]和对照组[（8．66±2．92）ng／m1]。②血清MPO水平，冠状动脉不同狭窄程度各组之间差异均存在显著统计学意义（F=25．95，P〈0．001），AMI组[（156．61±33．63）U／L]显著高于UAP组[（92．06±42．11）U／L]、SAP组[（80．02±20．28）U／L]和健康对照组[52．33±14．32）U／L]。③hs—CRP水平，重度狭窄组略高于与无狭窄组（3．61±0．64比1．41±0．55，P〈0．05）；AMI组hs—CRP水平[（5．74±1．09）mg／L]显著高于UAP组[（1．91±0．72）mg／L，P〈0．001]、SAP组[（2．61±0．60）mg／L，P〈0．01]和对照组[（1．47±0．47）mg／L，P〈0．001]。结论在冠心病不同程度冠脉狭窄组之间，血清MPO水平差异存在统计学意义，而sCD40L和hs—CRP水平差异无统计学意义；在冠心病不同程度病情组之间，血清sCD40L水平有统计学意义，而MPO和hs—CRP水平差异无统计学意义。     

Enhanced soluble CD40 ligand contributes to endothelial cell dysfunction in vitro and monocyte activation in patients with diabetes mellitus: effect of improved metabolic control

Aims/hypothesis Inflammation plays a pathogenic role in the development of accelerated atherosclerosis in diabetes. Soluble CD40 ligand (sCD40L) is enhanced in diabetes; however, the molecular mechanisms linking sCD40L to accelerated atherosclerosis in diabetes are still unclear. We tested the hypothesis that sCD40L may be involved in the vascular complications in diabetes and exerts its effect by triggering inflammatory reactions on mononuclear and endothelial cells (ECs).Methods We studied 70 patients, 40 with type 2 and 30 with type 1 diabetes, with a history or physical examination negative for cardiovascular disease, and 40 non-diabetic and 30 healthy subjects, matched with the type 2 and type 1 diabetic patients, respectively. Plasma and serum sCD40L, and plasma soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin and monocyte chemo-attractant protein-1 (MCP-1) were measured. Adhesion molecules and MCP-1 release, the ability to repair an injury in ECs, and O₂^– generation in monocytes were analysed in vitro after stimulation with serum from patients or controls.Results Type 2 and type 1 diabetic patients had significantly higher sCD40L levels than controls. Furthermore, high sCD40L was associated with in vitro adhesion molecules and MCP-1 release, impaired migration in ECs and enhanced O₂^– generation in monocytes. Improved metabolic control was associated with a reduction of plasma sCD40L by 37.5% in 12 type 1 diabetic patients. Furthermore, elevated sCD40L in diabetic patients was significantly correlated with HbA₁c levels.Conclusions/interpretation Upregulation of sCD40L as a consequence of persistent hyperglycaemia in diabetic patients results in EC activation and monocyte recruitment to the arterial wall, possibly contributing to accelerated atherosclerosis development in diabetes.     

Elevated levels of biologically active soluble CD40 ligand in the serum of patients with chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is an indolent lymphoproliferative disorder manifested by low growth fraction and prolonged survival of the malignant cells. The mechanisms that enable CLL cells to live longer and to resist apoptosis remain unclear. Because the malignant CLL cells express CD40 and Fas receptors, which can transduce cell-survival and cell-death signals, we examined the role of CD40 in the growth regulation of CLL cells and its interaction with Fas-mediated and fludarabine-induced apoptosis in vitro . Primary CLL cells underwent spontaneous apoptosis in culture, which was enhanced by exogenous human Fas ligand (FasL) or fludarabine. Exogenous CD40L rescued CLL cells from spontaneous apoptosis in a dose-dependent manner, and caused CLL cells to resist apoptosis induced by FasL or fludarabine. Patients' autologous plasma rescued CLL cells from spontaneous apoptosis, an effect that could be reversed with anti-CD40 ligand (CD40L) antibodies. The levels of soluble CD40 ligand in the sera of 51 CLL patients and 55 healthy donors were determined by enzyme-linked immunosorbent assay. The mean soluble CD40L level in normal donors was 0.29 ng/ml compared to a mean value of 0.80 ng/ml in CLL patients ( P  < 0.001). CD40L up-regulated bcl-X_L mRNA but not bcl-2 in CLL cells within 3–6 h in culture. Our results demonstrated that serum of patients with CLL contained elevated levels of biologically active soluble CD40L, and that CD40L can prolong survival of CLL cells and mediate their resistance to FasL and fludarabine in vitro .     

Increased serum soluble CD40 levels in patients with systemic sclerosis

OBJECTIVE: To determine serum levels of soluble CD40 (sCD40) and clinical association in patients with systemic sclerosis (SSc). METHODS: Serum sCD40 levels were examined by ELISA in 49 patients with SSc, 15 patients with systemic lupus erythematosus, and 26 healthy individuals. sCD40 levels in plasma samples, which were obtained at the same time, were also determined. SSc patients were grouped into 22 patients with limited cutaneous SSc (lcSSc) and 27 patients with diffuse cutaneous SSc (dcSSc). RESULTS: There was no significant difference between sCD40 levels of sera and those of plasma. Serum sCD40 levels were significantly elevated in patients with SSc compared to patients with systemic lupus erythematosus and controls (p < 0.001). Serum sCD40 levels were higher in patients with lcSSc than in those with dcSSc (p <0.001). There was no correlation between sCD40 and sCD40 ligand levels in patients with SSc. CONCLUSION: Elevated serum sCD40 levels were associated with lcSSc. These results suggest that the blockade of CD40/CD40 ligand interaction could be a potential therapeutic strategy in SSc.