sFas与sFasL在自身免疫疾病中的意义

目的　研究sFas与sFasL在系统性红斑狼疮 (SLE)等自身免疫疾病中的意义及抗单链DNA(ssDNA)抗体与sFas和sFasL介导凋亡的相关性。方法　采用夹心ELISA方法检测 31例SLE病人 ,32例类风湿关节炎 (RA)病人 ,2 0例 1型糖尿病 (IDDM )病人及 5例多发性硬化病 (MS)病人血清中sFas与sFasL含量及抗ssDNA抗体水平。结果　在SLE、RA、IDDM及MS患者血清中的sFas含量 (pg/ml)分别为 2 881± 16 5 3 ,988± 6 96 ,135 2± 413 ,15 40± 5 6 6 ,明显高于正常对照 (P <0 0 0 2 ) ,SLE病人sFas含量高于RA ,MS ,IDDM病人。SLE、RA患者血清sFasL含量 (pg/ml)分别为5 35± 431、12 38± 1184,明显高于正常对照 (P <0 0 2 ) ,MS、IDDM患者血清sFasL含量 (pg/ml)分别为 2 5 1± 140 ,2 11± 73 ,低于正常对照 (P >0 0 5 )。在SLE、RA病人中 ,高浓度sFasL者伴有高浓度sFas。在SLE病人中 ,所有抗ssDNA抗体阳性者均伴有高浓度sFas,所有抗sFas阴性者 ,ssDNA抗体也为阴性。结论　在SLE等疾病中sFas水平明显高于正常人 ,可作为疾病进展与治疗效果的判断指标。抗ssDNA抗体与sFas具有关联性。sFas与sFasL在疾病中的相互作用及动态变化有待进一步研究     

Hyperferritinemia as indicator for intravenous immunoglobulin treatment in reactive macrophage activation syndromes

The underlying mechanisms of reactive macrophage activation syndromes (rMAS) are not understood in detail, and there is no specific treatment. This observational study was prompted by intravenous immunoglobulin (IVIG), dramatically halting two distinct rMAS episodes in the same patient. We evaluated the potential benefits of IVIG administration in treating fulminant rMAS and the usefulness of monitoring serum ferritin levels as an indication for emergency treatment with IVIG. Ten females and 10 males experiencing 22 episodes of rMAS were recruited on the basis of serum ferritin levels >or=10,000 microg/l and/or direct evidence of haemophagocytosis in 11 intensive care units in secondary and tertiary care hospitals in Switzerland between October 1993 and May 2000. In individual patients, serially measured ferritin was closely related to disease activity. Abrupt increases of up to >100,000 microg/l could be observed within hours. Rapid and profound beneficial effects of emergency IVIG treatment were seen in 12 episodes of rMAS accompanied by a prompt decrease of serum ferritin. IVIG produced partial or delayed improvements in 5 patients. No apparent effects were seen in 5 patients. IVIG was only successful if started early during the ferritin run-up to peak values. In conclusion, IVIG is effective in at least a subgroup of adult rMAS when started at the beginning of the macrophage activation process. The monitoring of serum ferritin levels might be helpful in detecting macrophage activation in order to commence IVIG treatment early enough.     

Circulating levels of soluble Fas ligand and soluble Fas in patients with chronic obstructive pulmonary disease

Fas- and tumour necrosis factor (TNF) receptor-mediated apoptosis are known to be two principal apoptotic mechanisms in humans. Although there are several distinctions between these two systems, in vitro studies have demonstrated similar hypoxic activation and a functional relationship. Since patients with chronic obstructive pulmonary disease (COPD) show chronic hypoxaemia and the activation of the TNF-alpha system, we investigated whether these pathophysiological changes influence the Fas-Fas ligand system. We measured the circulating soluble Fas ligand (sFas-L) level, an inducer of apoptosis, and the soluble Fas receptor (sFas) level, an inhibitor of apoptosis, in 34 COPD patients and 35 age-matched healthy controls. In addition, we investigated the relationships between the levels of sFas-L or sFas and clinical variables including the TNF-alpha system; circulating TNF-alpha and soluble TNF-receptor (sTNF-Rs: sTNF-R55 and R75) levels, in the COPD patients. Although circulating TNF-alpha, sTNF-R55 and R75 levels were significantly higher in the COPD patients than in the healthy controls, serum level of sFas-L (Fisher's exact probability test; P = 0.26) and plasma level of sFas [COPD patients vs. controls; mean (SD); 3.74 (0.63) vs. 3.67 (0.48) ng/ml; P = 0.89) were not increased in the COPD patients. There was no significant correlation between the levels of sFas-L or sFas and clinical variables in COPD patients. These results suggest that the Fas-Fas ligand system does not independently play an important role in the pathophysiology of patients with COPD.     

Role of soluble Fas ligand in autoimmune diseases

AIM: To investigate the role of soluble Fas ligand in autoimmune diseases. METHODS: RT-PCR was performed to amplify sFasL cDNA from the total RNA extracted from activated human peripheral blood lymphocytes. DNA fragments were cloned into PCR vector. After sequenced, sFasL gene fragments were inserted into pQE-31 vector and expressed in E. Coli M15 respectively. Proteins were purified through affinity chromatography column with ligand of 6XHis tag and identified by SDS-PAGE and Western blot. Mice were immunized with sFasL protein and specific anti-serum was harvested 6 wk after immunization. Monoclonal anti-human FasL antibody was made from the immunized mice. Serum level of sFasL in different patients was detected using anti-FasL antibodies from the immunized mice. RESULTS: The protein expressed was 24 ku by SDS-PAGE electrophrosis. The protein was specially bound to anti-human FasL antibody by Western blot analysis. The sFasL protein could induce Jurket cell apoptosis in vitro. The concentration of serum sFasL in patients with autoimmune diseases was higher than that in normal individuals. sFasL could reduce arthritis in collagen induced arthritis (CIA) mice model by subcutaneous injection. CONCLUSION: sFasL may be involved in either induction of apoptosis or autoimmune diseases. Furthermore, sFasL may have potential application in treatment of autoimmune diseases.     

血清sFas、sFasL水平与特发性血小板减少性紫癜的关系

采用酶联免疫夹心法(ELISA)检测了25例特发性血小板减少性紫癜(ITP)患者血清中sFas、sFasL的水平.结果显示ITP患者血清sFas含量为16.51±6.86μg/L,sFasL含量为0.48±0.33μg/L,均显著高于正常对照(分别为P<0.001和P<0.01);18例ITP患者血清sFas水平升高,其中有9例同时有sFasL水平升高,但是血清sFas水平升高组的血小板计数与sFas正常组无显著差异.提示sFas和sFasL的异常参与了ITP的免疫病理过程.     

The evaluation of soluble Fas and soluble Fas ligand levels of bronchoalveolar lavage fluid in lung cancer patients

Fas-Fas Ligand (FasL) is one of the major mediator system that activates programmed cell death. Cleavage of membranebound FasL by a metalloproteinase-like enzyme resulted in the formation of soluble FasL (sFasL). sFasL as well as the transmembrane form of FasL binds to Fas and transduces apoptotic signal in Fas-expressing cells. It's suggested that soluble Fas (sFas) and sFasL has an impact on tumor progress and immune escape feature of tumor cells from the host immune system. Since Fas antigen expression in the lungs has been localized to alveolar and bronchial epithelial cells, in this study we aimed to investigate the sFas (pg/mL) and sFasL levels (pg/mL) of bronchoalveolar lavage (BAL) fluid in lung cancer patients. Study population was consisted of 27 patients with lung cancer (mean age 62.9 +/- 10.7 years, 25 control subjects (mean age 47.9 +/- 13.9 years). BAL was performed under local anesthesia, on the unaffected lung of patients; either subsegments of right middle or lingula. BAL sFas and sFasL were evaluated by using ELISA method. The mean levels of sFas was 60.8 +/- 56.8 in lung cancer patient and 39.5 +/- 25.9 in control subjects (p> 0.05). The mean levels of sFasL was 51.6 +/- 39.2 in cancer patient and 41.2 +/- 27.4 in control subjects (p> 0.05). In conclusion, although we did not observe any significant difference between two groups, higher BAL levels of sFas and sFasL levels in lung cancer patients than control subjects, made us thought that apoptosis might have a role development and progression of lung cancer.     

慢性心力衰竭患者的血清可溶性Fas配体和可溶性Fas受体

目的 分析血清可溶性Fas配体(sFasL)和可溶性Fas受体(sEas)与慢性心力衰竭(CHF)的相关性。方法采用酶联免疫吸附双抗体夹心法检测33例CHF患者(CHF组,心功能Ⅱ-Ⅳ级,NYHA)血清sFasL和sFas浓度,并与18例心功能Ⅰ级(NYHA)组比较。结果 CHF与心功能Ⅰ级间sFasL浓度无显著统计学差异[231.50±84.50(心功能Ⅱ级216.50±96.00,Ⅲ级226.80±85.70,Ⅳ级244.00±73.00)vs217.50±89.00pg/mL,P>0.05]。而CHF组血清sFas浓度显著高于心功能Ⅰ级组[1353.30±507.71(心功能Ⅱ级1154.85±371.20,Ⅲ级1412.88±493.62,Ⅳ级1875.67±806.10)vs983.11±461.26pg/mL,P<0.05]。结论 血清sFasL与CHF无相关性。而血清sFas与CHF存在显著相关性。且sFas浓度增高的程度与CHF的严重程度相平行,sFas浓度增高可能在CHF发病机制中起重要作用。     

Cord blood soluble Fas ligand and pediatric atopic dermatitis

Keratinocyte apoptosis is a key pathogenetic mechanism in atopic dermatitis (AD). Fas and Fas ligand (FasL) interaction is an important pathway to induce apoptosis. However, the relationship between early life soluble FasL (sFasL) and AD still is not clear. This study was designed to evaluate if sFasL is associated with the development of AD in children. We performed a nested case-control study within a prospective Taiwan birth-panel cohort study. Umbilical cord blood and maternal plasma samples were gathered at birth. During follow-up, using the International Study of Asthma and Allergies in Childhood questionnaires, we identified 40 AD cases, which we matched to 80 unaffected controls chosen from this cohort. The concentrations of sFasL and immunoglobulin E in plasma were determined by enzyme-linked immunosorbent assay. The relationship of sFasL levels and AD was estimated by mix model. Receiver operating characteristic (ROC) curves were generated to see how well sFasL could predict AD. Cord blood sFasL levels were significantly higher in the AD patients than in the controls (p = 0.003). The concentration of sFasL in the cord blood was higher than in the maternal blood (p < 0.001). There also existed a correlation between the concentration of sFasL in the maternal blood and the cord blood (r = 0.23; p = 0.01). The subjective severity of AD was positively correlated with sFasL levels (r = 0.34; p = 0.02). Cold blood sFasL may be a biomarker in detecting pediatric AD (area under the ROC curve = 0.64). Our results showed a relation between cord blood sFasL and the development of AD in children.     

可溶性Fas,可溶性Fas配体与细胞因子在1型糖尿病发病中的意义

目的　研究可溶性Fas(sFas)和可溶性Fas配体(sFasL)与细胞因子在1型糖尿病发病中的作用。方法　32名1型糖尿病患者和20名正常人的血清,采用夹心BAS-ELISA法分别检测sFas,sFasL,γ干扰素(IFN-γ)及白细胞介素-1(IL-1)含量。结果　1型糖尿病血清中sFas,IFN-γ及IL-1含量分别为(1　　546±685,1　　074±451与1　　406±721)ng/L,显著高于正常组;sFasL为(211±73)mg/L,低于正常组但差异无显著性。在1型糖尿病患者中高浓度sFas伴高IFN-γ者共12例,低浓度sFas伴低IFN-γ者共9例。结论　1型糖尿病患者血清中的sFas,IFN-γ及IL-1高于正常人,sFas与IFN-γ浓度呈正相关(r=0.79,P＜0.05)。对1型糖尿病患者血清进行sFas,IFN-γ及IL-1等检测可作为反映胰岛细胞病变的辅助指标,有助于对疾病的诊断与治疗。     

Expression of Fas receptor and soluble Fas ligand (sFasL) concentration in acute leukemia

Apoptosis mediated by the interaction of cytotoxic T lymphocyte with blast cell via Fas receptor/Fas ligand (FasL) pathway is a one of the mechanisms of immunological leukemia surveillance. There is few data on possible blocking of Fas receptor by soluble form of Fas (sFasL) present in serum and the role of blast cells as the source of this ligand. Forty-eight patients with de novo diagnosis of acute leukemia, 32 with myeloblastic (AML) and 16 with acute lymphoblastic leukemia (ALL) were studied. Fas expression on bone marrow leukemic blasts was determined by flow cytomertic immunofluorescent analysis and serum concentration of sFasL assessed at presentation, in remission and in relapse. Blasts of all patients expressed Fas at variable degree (0.8 to 100%). Fas expression was significantly higher on myelo--than on lymphoblasts. There was no relation between degree of Fas expression at diagnosis and remission rate. Concentration of sFasL in acute leukemia patients at diagnosis was significantly higher than in healthy control group, decreased to normal values in remission and rose again in relapse. There was a negative correlation between Fas expression on blasts and sFasL concentration at the time of diagnosis. Results obtained suggest that blast cells could be the source of soluble FasL in acute leukemia patients and that sFasL serum concentration could be used for monitoring of disease activity.     

Role of serum soluble Fas/soluble Fas ligand and TNF-alpha on response to interferon-alpha therapy in chronic hepatitis C

AIMS/BACKGROUND: To determine the relationship between host factors and host response to interferon (IFN) therapy, serum soluble Fas (sFas), soluble Fas ligand (sFas ligand), and tumor necrosis factor-alpha (TNF-alpha) were analyzed in 41 patients with chronic hepatitis C (CH-C) treated with IFN-alpha. METHODS: Serum levels of sFas, sFas ligand, and TNF-alpha were measured at 0, 4, and 24 weeks of IFN therapy. RESULTS: Eighteen patients were complete responders (CR) and 23 patients were non-responders (NR). Serum levels of sFas and TNF-alpha in patients with CHC were significantly higher than those in healthy controls (p<0.01 and p<0.01, respectively). Serum sFas ligand levels were significantly lower in CH-C patients than in healthy controls (p<0.01). Before IFN therapy, serum levels of sFas in NR were significantly higher than those in CR (p<0.05). At 4 weeks of IFN therapy, serum levels of sFas of CR were significantly elevated compared with levels before IFN therapy (p<0.05). Serum levels of sFas correlated with the histological activity of the liver (p<0.05) and alanine aminotransferase (p<0.05). None of the three parameters, serum sFas, sFas ligand, or TNF-alpha levels, correlated with each other, with HCV-RNA genotype or with serum HCV-RNA load. Multiple logistic regression analysis showed that serum sFas levels before IFN therapy were a contributive factor to predict efficacy of IFN therapy. CONCLUSIONS: Serum sFas/sFas ligand and TNF-alpha play a possible role in pathogenesis of CH-C and also in IFN therapy. Serum sFas levels before IFN therapy may be one of the host-related factors used for evaluating the response of CH-C patients to IFN therapy.     

Increased levels of soluble Fas receptor and Fas ligand in the cerebrospinal fluid of HIV-infected patients

Analyses of serum samples and blood cells have revealed a dysregulation of the Fas/Fas ligand (FasL) system during HIV infection, which may be related to disease progression. As Fas and FasL have been suggested to participate in brain injury in a variety of CNS disorders, the aim of this study was to determine (1) whether soluble Fas and FasL can be detected in cerebrospinal fluid (CSF) samples from HIV-infected patients, (2) whether levels of these molecules are related to disease progression, and (3) whether levels of sFasL are related to other laboratory findings. Soluble Fas was detected in 38 of 56 (68%) and soluble Fas ligand in 17 of 56 (30%) CSF samples from HIV-infected patients. CSF levels of both molecules correlated neither with the CSF-to-serum albumin ratio nor with corresponding serum concentrations. This finding suggests that they are at least in part produced intrathecally. Levels of both CSF sFas and sFasL correlated significantly and inversely with the blood CD4+ cell counts, suggesting that the intrathecal release of both molecules is increased during progression to advanced immunodeficiency.     

狼疮肾炎患者血清sFas和sFasL的变化

目的　研究狼疮肾炎患者血清sFas和sFasL的变化及意义。方法　采用双抗体夹心酶联免疫吸附法 (ELISA)检测正常对照 18例和狼疮肾炎患者 45例血清sFas和sFasL水平。结果　狼疮肾炎患者sFas和sFasL水平分别为 (14± 7) μg/L和 (0 0 7± 0 0 4) μg/L ,与正常对照组 (2 9±1 2 ) μg/L和 (0 0 5± 0 0 1) μg/L相比 ,差异有高度显著性意义 (P <0 0 1)。活动期sFas水平较缓解期明显增高 ,分别是 (17± 7) μg/L和 (9± 4) μg/L ,P <0 0 1;但sFasL活动期与缓解期差异无显著意义。狼疮肾炎血清sFas水平在白细胞减少、贫血、大量蛋白尿、肾功能减退、补体降低、ANA和抗RNP Ab阳性时升高 ;而sFasL仅在肾功能异常时减低 ,与其他指标没有明显相关性。结论　sFas及sFasL参与了狼疮肾炎的发生 ,sFas可作为狼疮肾炎的活动性实验室指标。     

Clinical implications of circulating soluble Fas and Fas ligand in patients with acute myocardial infarction.

BACKGROUND: Apoptotic cell death is the major form of myocardial damage produced by coronary ischemic events. OBJECTIVE: To assess whether circulating levels of soluble Fas (sFas), an inhibitor of apoptosis, and sFas ligand, an inducer of apoptosis, in patients with coronary artery disease are greater than normal. METHODS: Forty-seven patients [acute myocardial infarction (AMI) in 17, old myocardial infarction (OMI) in 15, stable angina in 15] and 10 normal control subjects participated in this study. Serum levels of sFas and sFas ligand in all patients were measured, and cardiac catheterizations were performed. RESULTS: Serum levels of sFas were greater than normal only in patients with AMI (4.6 +/- 1.6 ng/ml); the levels were significantly higher than those in patients with OMI (2.1 +/- 0.6 ng/ml) and stable angina (2.2 +/- 0.5 ng/ml), and in normal subjects (2.0 +/- 0.6 ng/ml; P < 0.0001). However, there was no difference among serum levels of sFas ligand for all groups. For patients with AMI, there was no significant correlation between serum levels of sFas and peak levels both of plasma creatine phosphokinase and of plasma myosin light chain type I as clinical indexes of infarct size. However, there were significant correlations between serum levels of sFas and both pulmonary artery wedge pressure (r = 0.767, P = 0.0003) and left ventricular end-diastolic pressure (r = 0.629, P = 0.03). CONCLUSIONS: Circulating sFas increases in concentration in relation to the severity of hemodynamic conditions in patients with AMI, but it is independent from size of infarct. Therefore, circulating sFas could play an important role as the marker of pathophysiologic conditions associated with cardiomyocyte apoptosis in AMI.     

Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fas ligand system in patients with chronic heart failure

OBJECTIVES: We sought to investigate the effects of physical training on circulating proinflammatory cytokines and the soluble apoptosis mediators Fas (sFas) and Fas ligand (sFasL) in patients with chronic heart failure (CHF). BACKGROUND: Recent investigations have shown an overexpression of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with CHF, which may be related to their exercise intolerance and clinical deterioration. METHODS: Plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors I and II (sTNF-RI and sTNF-RII, respectively), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sFas and sFasL were measured in 24 patients with stable CHF (New York Heart Association functional class II/III; left ventricular ejection fraction 23.2 +/- 1.3%) and in 20 normal control subjects before and after a 12-week program of physical training in a randomized, crossover design. Functional status of patients with CHF was evaluated by using a cardiorespiratory exercise test to measure peak oxygen consumption (VO2max). RESULTS: Physical training produced a significant reduction in plasma levels of TNF-alpha (7.5 +/- 1.0 pg/ml vs. 4.6 +/- 0.7 pg/ml, p < 0.001), sTNF-RI (3.3 +/- 0.2 ng/ml vs. 2.7 +/- 0.2 ng/ml, p < 0.005), sTNF-RII (2.6 +/- 0.2 ng/ml vs. 2.3 +/- 0.2 ng/ml, p = 0.06), IL-6 (8.3 +/- 1.2 pg/ml vs. 5.9 +/- 0.8 pg/ml, p < 0.005), sIL-6R (34.0 +/- 3.0 ng/ml vs. 29.2 +/- 3.0 ng/ml, p < 0.01), sFas (5.5 +/- 0.7 ng/ml vs. 4.5 +/- 0.8 ng/ml, p = 0.05) and sFasL (34.9 +/- 5.0 pg/ml vs. 25.2 +/- 4.0 pg/ml, p < 0.05), as well as a significant increase in VO2max (16.3 +/- 0.7 ml/kg per min vs. 18.7 +/- 0.8 ml/kg per min, p < 0.001). Good correlations were found between a training-induced increase in VO2max and a training-induced reduction in levels of the proinflammatory cytokine TNF-alpha (r = -0.54, p < 0.01) and the apoptosis inducer sFasL (r = -0.57, p < 0.005) in patients with CHF. In contrast, no significant difference in circulating cytokines and apoptotic markers was found with physical training in normal subjects. CONCLUSIONS: Physical training reduces plasma levels of proinflammatory cytokines and the sFas/sFasL system in patients with CHF. These immunomodulatory effects may be related to the training-induced improvement in functional status of patients with CHF.     

胃癌患者血清可溶性FasL的变化及意义

应用双抗体夹心酶联免疫吸附法(ELISA)检测45例胃癌患者血清中可溶性FasL(sFasL)水平,并取30例健康献血员为对照。结果显示,胃癌患者术前血清sFasL为(15.24±1.25)μg/L,30例健康献血员sFasL病理为(4.21±1.13)μg/L。两组比较P<0.01。胃癌患者术前血清sFasL含量[(15.24±1.25)μg/L]显著高于术后(5.36±1.19)μg/L],P <0.01,且分期越高、分化程度越低、有淋巴结转移、肿瘤直径>3cm者,术前血清sFasL越高。提示胃癌患者血清中含有sFasL,且sFasL在胃癌免疫逃逸、反击机制中起重要作用;术前胃癌血清中sFasL水平可作为术后随访和判断预后的一个重要指标。     

Elevated serum soluble Fas ligand in natural killer cell proliferative disorders

We evaluated the serum level of soluble Fas ligand (sFasL) in patients with natural killer lymphocyte proliferative disorders (NK- LPD). The serum sFasL level was elevated in neoplastic groups of aggressive NK leukaemia, indolent NK leukaemia and NK lymphoma, all of which contained clonal EBV-DNA. In NK leukaemia the serum sFasL level was significantly higher than that found in others. However, it was not elevated in the patients with reactive NK-LPD and in one patient with NK leukaemia in remission. These findings indicate that the serum sFasL level is a useful indicator in evaluating disease activity.     

Circulating soluble Fas ligand correlates with disease activity in Graves' hyperthyroidism

Apoptosis of thyrocytes may play an important role in the pathogenesis of autoimmune thyroiditis. Meanwhile, the Fas/Fas ligand (FasL) apoptosis pathway has received much attention in physiological homeostasis and immune regulation in various thyroid diseases, including Graves' hyperthyroidism (GD). FasL is a type II membrane protein of the tumor necrosis factor family, and induces apoptosis when it binds to Fas. Soluble FasL (sFasL) may also exert cytotoxic activity against Fas-expressing cells by producing trimerization of Fas molecule, but soluble Fas (sFas) is an apoptotic inhibitor. To determine the role of circulating sFas/sFasL in modulating disease activity of GD, we examined the circulating levels of sFas/sFasL in GD patients with various levels of anti-thyrotropin-stimulating hormone (TSH) receptor antibodies (TRAb). Serum samples were obtained from 22 consecutive untreated hyperthyroid GD patients with higher TRAb level (63.8% +/- 12.5%, group I) and 22 treated euthyroid GD patients, who were in a state of disease remission, with lower TRAb level (7.9% +/-5.9%, group II). The levels of sFas were significantly higher in group I (1.56 +/- 0.26 ng/mL) than in group II (0.76 +/- 0.26 ng/mL, P <.01). The levels of sFasL were also significantly higher in group I patients (0.153 +/- 0.018 ng/mL) than in group II patients (0.126 +/- 0.012 ng/mL, P <.01). A significant correlation was found between sFasL levels and TRAb activity in all GD patients (r = 0.69, P <.01). Because changes in sFasL levels and TRAb levels occur in parallel, increased serum sFasL in patients with GD may contribute to homeostasis in the thyroid. Serum sFasL may be considered to be a candidate marker for evaluating disease aggression or regression in GD.     

Plasma-soluble Fas (APO-1, CD95) and soluble Fas ligand in immune thrombocytopenic purpura

We investigated the levels of various cytokines and soluble factors in ITP patients, in order to determine the influence of these factors on the pathogenesis of ITP. We found increases in IL-2, IL-6, IFN-gamma, and M-CSF levels in ITP patients compared with those in healthy individuals. On lymphocyte phenotype analysis, we found no clear difference in total T cell population (CD2+ CD19- cells) or cytotoxic T cell frequency (CD8+ CD11b- cells) between these two groups. The frequency of helper/inducer T cells (CD4+ CD8- cells) was decreased in ITP patients. There was a significant increase in activated T cells (CD3+ HLA-DR+ cells) in ITP patients. Furthermore, frequencies of NK cells of potent activity (CD16+ CD56+ cells) were significantly elevated in ITP patients. Seventeen of the 54 ITP patients (31.5%) had elevated levels of sFas, and 11 of the 54 patients (20.4%) of sFasL. In addition, a significant increase of sFasL was observed in sFas-positive ITP patients, and in these patients the sFasL level was correlated with that of sFas (r = 0.687, p < 0.01). We found significant increases in IL-2 and sIL-2R levels in sFas-positive ITP patients. For other factors examined, however, there were no differences in level between sFas-positive and -negative ITP patients. Percentages of activated T cells (CD3+ and HLA-DR+ cells) and NK cells (CD16+ and CD56+ cells) were significantly higher in sFas-positive ITP patients than in sFas-negative ITP patients. These findings suggests that the pathogenesis of ITP includes alteration of the Fas/FasL pathway.