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 .     

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.     

Analysis of serum soluble CD40 ligand (sCD40L) in the patients undergoing allogeneic stem cell transplantation: platelet is a major source of serum sCD40L

CD40 ligand (CD40L) is expressed not only on activated T cells but also on activated platelets. A soluble CD40 ligand (sCD40L) is released from the activated T cells and platelets by ill-defined proteolytic process in vitro. It has been reported that sCD40L is elevated in the serum of patients with systemic lupus erythematosus, unstable angina, essential thrombocythemia, and autoimmune thrombocytopenic purupura. However, source of sCD40L in vivo remains to be elucidated. We investigated the serial sCD40L in the serum in patients undergoing allogeneic stem cell transplantation and compared with the platelets number and soluble IL2R, which is a marker of activated T cells. The value of sCD40L was well correlated with platelet number or thrombopoiesis. In cases of severe graft vs. host disease with markedly increased sIL2R, sCD40L was not increased in vivo. These results indicate that sCD40L in vivo is released mainly from the platelets or in the process of platelet production but not from the activated T cells.     

Elevated circulating CD40L concentrations in patients with systemic sclerosis

OBJECTIVE: B cell activation, fibrosis, and expression of adhesion molecules on endothelial cells are regulated by soluble CD40L (sCD40L)/CD40 interactions. Since these effects are characteristic in patients with systemic sclerosis (SSc), serum concentrations of sCD40L were determined in patients with SSc. METHODS: Fifty-two Japanese patients with SSc were examined. They were grouped into 24 patients with limited cutaneous SSc (lSSc) and 28 with diffuse cutaneous SSc (dSSc). Serum sCD40L levels were examined by ELISA. As a disease control, serum samples from 20 patients with systemic lupus erythematosus (SLE) were also examined. In addition, a retrospective longitudinal study was performed in 71 serum samples from 18 patients with SSc. RESULTS: Serum sCD40L levels were elevated in SSc patients compared with healthy controls (p < 0.001). Levels of sCD40L in patients with SSc were higher than in patients with SLE (p < 0.001) that had elevated sCD40L levels compared with healthy controls. Among SSc subsets, there were no differences in sCD40L levels between lSSc and dSSc. sCD40L levels correlated positively with C-reactive protein levels in SSc patients (p < 0.0001, r = 0.449). In a cross-sectional study and a longitudinal study, serum sCD40L levels in dSSc patients were persistently elevated, although those in lSSc patients were temporarily elevated at the early phase of the disease process. CONCLUSION: Patients with SSc exhibited elevated sCD40L levels that may correlate with disease activity. These results suggest that CD40/CD40L interactions may be potential therapeutic targets in SSc.     

急性冠状动脉综合征患者sCD40L的变化及他汀类药物的影响

目的探讨急性冠状动脉综合征(ACS)患者血清可溶性CD40L(sCD40L)水平的变化及他汀类药物对其的影响。方法102例ACS患者随机分为2组:安慰剂组,辛伐他汀和普伐他汀组(他汀组)。用间接免疫荧光流式细胞术和酶联免疫吸附法(ELISA)及常规酶法分别测定2组患者用药前和用药2、4、6周后血清sCD40L水平及总胆固醇(TC)水平。结果(1)他汀组患者服药2,4及6周后血清sCD40L水平明显低于安慰剂组(均P<0.05)。(2)他汀组患者服药2、4、6周后血清sCD40L水平呈逐渐下降趋势,同用药前相比差异均有统计学意义(均P<0.05)。(3)他汀组患者服药2、4、6周后血浆TC水平与用药前相比差异均有统计学意义(均P<0.05)。(4)他汀组患者血清sCD40L水平的降低与血浆TC水平的降低无明显相关性(r=0.014,P>0.05)。结论他汀类药物能明显降低ACS患者体内sCD40L水平,对减轻炎症反应、稳定斑块有一定作用。     

sCD40L在大鼠梗阻性黄疸肝损伤中的作用

目的探讨可溶性CD40L（soluble CD40L,sCD40L）在大鼠梗阻性黄疸肝损伤中的作用及其与肝损伤严重程度的相关性。方法 雄性SD大鼠18只,随机分为模型组、抗CD40L单克隆抗体（anti-CD40LmAb）组和假手术组各6只。模型组开腹后游离出胆总管双重结扎即关腹;单抗组同样方法造模后给予腹腔注射anti- CD40LmAb;假手术组仅予游离出胆总管即关腹。分别检测3组大鼠术后不同时间的血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBIL）、结合胆红素（DBIL）水平,以及肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8）、sCD40L的浓度。结果 与模型组相比,单抗组血清ALT、AST、TNF-α、IL-8及sCD40L显著减低（P〈0．05）,而TBIL及DBIL水平差异无统计学意义（P〉0．05）。血清sCD40L与TNF-α、IL-8的水平呈正相关。结论 sCD40L可能参与梗阻性黄疸免疫肝损伤的启动阶段,阻断CD40／CD40L途径可能成为肝损伤治疗的有效方法之一,sCD40有望成为肝损伤程度的新指标。     

Soluble CD40L, platelet surface CD40L and total platelet CD40L in congestive heart failure: relationship to platelet volume, mass and granularity

Background. Many complications associated with congestive heart failure (CHF) have a thrombosis-related aetiology, which may involve platelets. The immune modulator pair CD40-CD40L has been proposed to be an important link between inflammation and thrombosis and may be important in the pathophysiology of CHF. Objective. To study soluble CD40L (sCD40L), platelet surface CD40L (%GCD40L) and total platelet CD40L (pCD40L) levels in CHF patients, their relationships to other platelet indices (platelet volume, mass and component) and to assess their prognostic value. Methods. We measured sCD40L (by ELISA); pCD40L (by a platelet lysate assay); platelet surface CD40L (%GCD40L) expression by flow cytometry; mean platelet volume (MPV), mean platelet mass (MPM) and mean platelet component (MPC); in 108 patients with stable CHF. Levels were compared with 37 ‘healthy controls’ and 63 ‘disease controls’. After a median follow-up period of 490 days, clinical endpoints were determined. Results. pCD40L was significantly higher in CHF than disease controls, but not sCD40L or %GCD40L levels. CHF patients and disease controls had higher MPV (one-way anova , P < 0.0001), whilst MPC was significantly lower in CHF patients (P < 0.0001), compared to healthy controls. All indices related to CD40L (i.e. sCD40L, pCD40L and %GCD40L) were neither related to disease severity or left ventricular ejection function, nor to clinical endpoints at follow-ups. Conclusion. Patients with stable CHF patients did not exhibit enhanced levels of CD40L and the latter did not predict clinical events at follow-up. The lack of difference in CD40L levels between CHF and disease controls suggests that CD40L may not have a major role in CHF per se, but in the comorbidities associated with CHF.     

Expression and release of CD27 in human B-cell malignancies

CD27, a transmembrane disulfide-linked 55-kD homodimer, belongs to the nerve growth factor-receptor family, a group of homologous molecules involved in lymphocyte differentiation and selection. It is expressed on mature thymocytes, peripheral blood T cells, and a subpopulation of B cells. We investigated the expression of CD27 on malignant B cells representative for a broad range of stages in physiologic antigen- independent and -dependent B-cell development. In normal lymphoid tissue CD27+ B cells were only found in the peripheral blood (29.8% +/- 10.8%, n = 13) and in germinal centers. With the exception of pro-B and the majority of pre-pre-B acute lymphocytic leukemias and of myelomas, CD27 expression of variable intensity was detected on almost all immature and mature malignant B cells tested. Moreover, using a sandwich enzyme-linked immunosorbent assay we could show the presence of sometimes very high (up to 6,000 U/mL; normal values < 190 U/mL) amounts of the soluble 28- to 32-kD form of CD27 (sCD27) in the sera of patients with B-cell malignancies. The highest levels of sCD27 were observed in patients with chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphomas. Most importantly, both in transversal and longitudinal studies, we found a strong correlation between sCD27 levels in the serum and tumor load, indicating that sCD27 can be used as a disease-marker in patients with acute and chronic B-cell malignancies.     

白藜芦醇对内皮细胞CD40途径的影响

目的：观察白藜芦醇对内皮细胞CD40途径活化后CD40和E-选择素表达的影响。方法：白藜芦醇（10μmol／L）预孵育人脐静脉内皮细胞（HUVEC）后,以可溶性CD40配体（sCD40L,10μg／m1）刺激,流式细胞术检测内皮细胞E-选择素和CD40分子的表达,半定量逆转录聚合酶链式反应（RT—PCR）检测E-选择素和CD40基因的转录。结果：sCD40L诱导内皮细胞E-选择素和CD40基因的显著转录和表达（P均〈0．01）,白藜芦醇显著抑制E-选择素和CD40基因的转录和表达（P〈0．05～〈0．01）。结论：结果提示白藜芦醇可能通过抑制CD40途径发挥抗动脉粥样硬化作用。     

CD40配体高表达与不稳定型心绞痛之间的关系

为了探讨不稳定型心绞痛患者外周血单核细胞表达CD40配体及血清可溶性CD40配体变化的临床意义。应用间接免疫荧光流式细胞术和双抗夹心酶联免疫测定法分别对正常对照组 16例、稳定型心绞痛 2 0例、不稳定型心绞痛 2 0例患者血单核细胞表达CD40配体及血清可溶性CD40配体水平进行检测。并观察血清可溶性CD40配体与冠状动脉病变程度的关系。结果发现 ,(1)不稳定型心绞痛组血单核细胞表达CD40配体明显较稳定型心绞痛组和对照组高 (P <0 .0 1) ,稳定型心绞痛组与对照组相比无差异 (P >0 .0 5 )。 (2 )不稳定型心绞痛组血清可溶性CD40配体水平明显较稳定型心绞痛组和对照组高 (P <0 .0 1) ,而稳定型心绞痛组与对照组相比亦有明显差异 (P <0 .0 5 )。 (3)经皮冠状动脉腔内成形术后血清可溶性CD40配体明显高于术前 (P <0 .0 1) ,但血单核细胞表达CD40配体无差异 (P >0 .0 5 )。 (4 )血清可溶性CD40配体水平与冠状动脉病变的复杂狭窄数相关 (r=0 .5 4,P <0 .0 1) ,而与狭窄的程度和范围无关。此结果提示 ,血清可溶性CD40配体升高对冠状动脉斑块的不稳定或破裂起重要作用 ,且可能是冠状动脉病变的活动性标志物。     

皮质下血管性认知功能障碍患者血清sCD40L水平的变化

目的 探讨皮质下缺血性脑血管病(SIVD)认知障碍患者血清中可溶性CD40配体(sCD40L)的水平及其与认知障碍、白质病变(WML)的相关性.方法 对SIVD中19例血管性痴呆(VD)患者、20例血管性无痴呆型认知损害(VCIND)患者及15例年龄及性别相当的健康老年人行认知功能测试,采用酶联免疫吸附法( ELISA)检测受试者血清sCD40L水平;同时行头颅MRI扫描,应用年龄相关白质改变分级方法,对WML评分,进一步分析sCD40L与认知功能、WML的关系.结果 ①SIVD两组与正常对照组相比,血清sCD40L浓度增高(P＜0.05),两组之间差异不显著(P＞0.05).②SIVD患者sCD40L水平与MMSE、MoCA、WML评分均无明显相关性(P＞0.05).结论 ①皮质下血管性认知障碍患者血清sCD40L水平较正常老年人均明显升高,sCD40L可能参与SIVD发生、发展;②血清sCD40L水平与认知功能损害、白质病变程度无明显相关.     

Soluble CD40 ligand in acute and chronic heart failure.

AIMS: Inflammatory cytokines may play a pathogenic role in heart failure (HF). CD40-CD40 ligand (CD40L) interactions are important in atherogenesis and based on its role in inflammation we sought to evaluate the role of CD40L in human HF. METHODS AND RESULTS: Serum levels of soluble (s) CD40L were measured in 236 patients with acute HF following myocardial infarction, treated with either angiotensin-converting enzyme (ACE)-inhibition or angiotensin II blockade and followed for 2 years, and in 116 patients with chronic HF. Our main findings were: (i) patients with acute HF had increased sCD40L levels, particularly those with severe HF, diabetes, or hypertension; (ii) when these patients were followed longitudinally, persistently raised sCD40L levels were found throughout the observation period with no effect of captopril or losartan; (iii) the increase in sCD40L during follow-up was not seen in patients receiving warfarin therapy; (iv) patients with chronic HF also had raised sCD40L, significantly correlated with clinical severity, neurohormonal dysregulation, and left ventricular dysfunction; (v) studies from different blood compartments suggest that the vasculature of lower extremities and the failing myocardium itself may produce and secrete sCD40L in chronic HF. CONCLUSION: Our findings may suggest a pathogenic role for enhanced CD40-CD40L interactions in human HF.     

炎性因子CD40配体在急性冠脉综合征患者中的作用

目的探讨急性冠脉综合征（ACS）患者血清可溶性CD40配体（sCD40L）和超敏C反应蛋白（hs-CRP）的水平及临床意义。方法按照诊断标准入选研究对象137例,分为两组：冠状动脉造影无异常者为对照组,21例,ACS组116例,男86例,30例,年龄35～77（56.9±12.6）岁,包括不稳定型心绞痛88例,急性心肌梗死28例。采集患者空腹肘静脉血,采用酶联免疫吸附（ELISA）方法测定血清sCD40L浓度和hs-CRP浓度。所有患者入院第2～4天行冠状动脉造影检查,用直径法测定冠状动脉狭窄的程度,用Gensini评分系统进行评分,累计积分。结果 ACS组sCD40L与hs-CRP水平均高于对照组（P＜0.05）。sCD40L水平与Gensini积分呈正相关关系（r＝0.328,P＝0.000）,hs-CRP水平与Gensini积分呈正相关关系（r＝0.748,P＝0.000）,sCD40L与hs-CRP之间呈正相关关系（r＝0.192,P＝0.039）。结论 ACS患者外周血清sCD40L和hs-CRP水平明显升高,提示CD40/CD40L系统与ACS的发生有关。     

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.     

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.     

Role of the CD40 and CD95 (APO-1/Fas) antigens in the apoptosis of human B-cell malignancies

Ligation of CD40 inhibits apoptosis and stimulates proliferation of normal B cells, whereas ligation of CD95 (APO-1/Fas) induces apoptosis of activated lymphocytes. Aberrant signalling through the CD40 and CD95 antigens could thus participate in the pathogenesis of lymphoid malignancies. The expression and function of CD40 and CD95 on neoplastic B cells from patients with acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL) and non-Hodgkin’s lymphoma (NHL) were examined. CD40 was expressed by all 30 B-cell tumours, whereas CD95 was detected on neoplastic B cells in only one of 10 cases of ALL, two of 10 cases of CLL, and three of 10 cases of NHL. Incubation with an agonistic CD95 monoclonal antibody (MoAb) did not augment apoptosis in any of the unstimulated B-cell neoplasms. CD40 triggering did not consistently inhibit spontaneous apoptosis, but ultimately stimulated the growth of neoplastic B cells in most cases. Furthermore, CD40 activation led to up-regulation of the CD95 antigen in all 30 B-cell neoplasms. Ligation of CD95 on CD40-activated tumour cells augmented apoptosis in five of 10 ALL, three of 10 CLL, and nine of 10 NHL cases. The degree of apoptosis induced by CD95 triggering was greater for NHL cells than for ALL cells or CLL cells. Bcl-2 expression by ALL and NHL cells was substantially decreased after in vitro culture, whereas Bcl-2 expression by CLL cells was not significantly changed. However, there was no correlation between the level of Bcl-2 expression and sensitivity to CD95-mediated apoptosis. Thus, factors other than levels of CD95 and Bcl-2 determine susceptibility of malignant B cells to apoptosis after CD95 triggering. CD40-activated lymphoma cells appear to be very sensitive to CD95-mediated apoptosis, suggesting potential strategies for treatment of NHL. Elucidation of the mechanisms underlying resistance of ALL and CLL cells to CD95 triggering may facilitate the development of novel therapeutic approaches to these diseases as well.     

Significance of chemokines and soluble CD40 ligand in patients with autoimmune thrombocytopenic purpura

We investigated the levels of various chemokines and soluble CD40L (sCD40L) in ITP patients, in order to determine the influence of CD40-CD40L interaction on the pathogenesis of ITP. We found increases in MCP-1 and RANTES levels in ITP patients compared with those in healthy individuals. Thirty-eight of the 65 ITP patients (58.5%) had elevated levels of sCD40L. We found significant decreases in platelet counts in sCD40L-positive ITP patients. Although the sCD40L level did not differ significantly between the control and nonimmune thrombocytopenia groups, but among ITP patients. sCD40L level was significantly higher in those with untreated ITP than in those with treated ITP. In addition, significant increases in RANTES, MCP-1, sCD14, and sP-selectin levels were observed in sCD40L-positive ITP patients, although sE-selectin levels were not increased in such patients. For other factors examined, however, there were no differences in level between sCD40L-positive and -negative ITP patients. These findings suggests that there are two groups of ITP patients, one with elevated and one with normal of sCD40L. ITP cases in which sCD40L was increased appeared to involve changes in platelet counts and monocyte activation. The pathogenesis of ITP may in some patients include alterations of the CD40/CD40L pathway.     

原发性高血压患者血清CD40水平及脉搏波速率与CD40基因多态性的关系

目的：探讨原发性高血压患者CD40基因多态性与血清CD40水平及脉搏波速率的联系。方法：研究对象为432名原发性高血压患者。以酶联免疫反应法测定血清可溶性CD40（sCD40）水平。用Taqman聚合酶链式反应（PCR）方法测定CD40基因三种类型（A/G、C/T、T/C）,分析CD40基因多态性与血清CD40浓度、脉搏波速率（PWV）的联系。结果：有CD40基因A/G中的GA[GA：（43.4±4.2）pg/ml比AA：（29.6±1.6）pg/ml,GG：（39.8±6.5）pg/ml]、C/T中的CT[CT：（42.1±4.2）pg/ml比CC：（37.1±7.6）pg/ml,TT：（30.6±1.5）pg/ml]、T/C中的TT[TT：（43.3±5.3）pg/ml比TC：（32.3±1.3）pg/ml,CC：（30.7±3.7）pg/ml]等三种基因型的高血压患者的sCD40水平均较其他相应基因型显著升高（P〈0.05～0.01）;有A/G中的GG[GG：（9.5±0.3）m/s比AA：（9.0±0.1）m/s,GA：（8.8±0.1）m/s]、C/T中的CC[CC：（9.6±0.3）m/s比CT：（8.9±0.1）m/s,TT：（9.0±0.5）m/s]、T/C中的CC[CC：（9.3±0.2）m/s比TT：（9.0±0.1）m/s,TC：（8.9±0.1）m/s]等三种基因型的高血压患者的PWV均较其他相应基因型明显增快（P均〈0.05）。结论：CD40的三种基因多态性与血清CD40浓度、脉搏波速率有关。     

老年脑梗死患者血清可溶性CD40配体和白细胞介素18的变化及意义

目的探讨老年脑梗死患者血清可溶性CD40配体(sCD40L)、白细胞介素18(IL-18)及高敏C反应蛋白(hs-CRP)水平的变化及意义。方法选择急性脑梗死患者80例(脑梗死组),根据年龄分为老年脑梗死患者42例,非老年脑梗死患者38例;根据梗死面积分为腔隙性脑梗死患者38例,非腔隙性脑梗死患者42例;根据神经功能缺损评分分为重型患者16例,中型患者30例,轻型患者34例。同期健康体检者28例(对照组)。采用ELISA法和胶乳凝集法检测血清sCD40L、IL-18及hs-CRP水平。结果与对照组比较,脑梗死组老年脑梗死和非老年脑梗死患者血清sCD40L、IL-18及hs-CRP水平明显升高,腔隙性脑梗死和非腔隙性脑梗死患者血清sCD40L、IL-18及hs-CRP水平明显升高,神经功能缺损中型和重型患者sCD40L、IL-18及hs-CRP水平明显升高,差异有统计学意义(P<0.05,P<0.01)。血清sCD40L与IL-18呈正相关(r=0.7645,P<0.01)。结论脑梗死患者急性期血清sCD40L、IL-18、hs-CRP水平明显升高,且随年龄、梗死体积和神经功能缺损程度增加而加重,sCD40L可能上调IL-18表达,并参与脑梗死炎性反应过程。     

共刺激分子CD40/CD40L及B7/CD28与动脉粥样硬化

共刺激分子CD40/CD40L及B7/CD28是T细胞活化的两条重要辅助刺激通路,不仅在调节T细胞免疫反应中起关键作用,而且也在B细胞的活化、增殖、分化、抗体的分泌起重要作用.近年来它们在动脉粥样硬化方面的研究成为国内外学者研究的热点.对共刺激分子和动脉粥样硬化关系的深入了解,将有助于阐明动脉粥样硬化发生的炎症和免疫机制,并为临床治疗开辟新途径.本文综述了共刺激分子的免疫学特征及功能以及在动脉粥样硬化中发挥的作用与免疫学治疗的前景.