Antiphospholipid syndrome patients display reduced titers of soluble CD21 in their sera irrespective of circulating anti-β2-glycoprotein-I autoantibodies

A soluble form of the complement receptor CD21 (sCD21) is shed from the lymphocyte surface. The sCD21 is able to bind all known ligands such as CD23, sCD23, Epstein–Barr virus and C3d in immune complexes. Here, we show the serum levels of sCD21 in sera the of antiphospholipid syndrome (APS) patients. Antiphospholipid syndrome is an autoimmune disorder in which autoantibodies cause heart attack, stroke and miscarriage. Antiphospholipid syndrome may appear as primary or in association with systemic lupus erythromatosus (SLE) and other autoimmune diseases. Here, we ask whether APS patients have different sCD21 titers compared to healthy persons and whether sCD21 levels correlate with the presence of anti-β2-GPI autoantibodies. We show that autoimmune APS patients have significantly reduced amounts of sCD21 in their sera, irrespective of the presence of anti-β2-GPI autoantibodies. In our APS patients cohort additional SLE, vasculities, DVT (deep vein thrombosis), fetal loss or thrombosis did not correlate to the reduced level of sCD21.     

Decreased levels of serum soluble complement receptor-II (CR2/CD21) in patients with rheumatoid arthritis

OBJECTIVE: The soluble cluster of differentiation 21 (sCD21) represents the extracellular portion of the CD21 glycoprotein and is released by shedding from cell surfaces into plasma. Soluble CD21 binds complement fragments and activates monocytes through binding to membrane CD23. Elevated levels of sCD21 are found during Epstein-Barr virus EBV infections, B-cell lymphoma and other lymphoblastoid tumours. The present study was undertaken to investigate levels of sCD21 in rheumatoid arthritis. METHODS: A specific enzyme-linked immunoassay was developed using sCD21, biochemically purified to homogeneity from human plasma as a standard for the determination of sCD21 concentration in patient sera. Peripheral blood B and T lymphocytes were isolated from healthy donors and rheumatoid arthritis patients and cultured, and supernatants were analysed for CD21 shedding. RESULTS: The normal values of serum sCD21 in healthy individuals between 20 and 40 yr of age ranged from 100 to 477 ng/ml (median 292 ng/ml), decreasing with age but not differing with gender. In rheumatoid arthritis patients, sCD21 levels ranged from 50 to 300 ng/ml (median 182 ng/ml), did not differ with age and were independent of rheumatoid factor. CONCLUSIONS: In contrast to healthy donors, patients with rheumatoid arthritis have significantly lower sCD21 levels (P < 0.0001), independently of the age of the patients. Sorted B cells from rheumatoid arthritis patients released amounts of CD21 comparable with those of normal controls. Possible causes and consequences of the findings are discussed.     

Serum levels of soluble CD21 in patients with systemic sclerosis

Systemic sclerosis (SSc) is a systemic disorder that typically results in fibrosis of the skin and multiple internal organ systems. Although the precise mechanism is unknown, overproduction of extracellular matrix proteins, including collagens and fibronectins, and aberrant immune activation might be involved in the pathogenesis. The soluble cluster of differentiation 21 (sCD21) represents the extracellular portion of the CD21 glycoprotein that is released by shedding from the cell surfaces into plasma. sCD21 binds complement fragments and activates monocytes through binding to membrane CD23. The present study was undertaken to investigate the serum levels of sCD21 in patients with SSc. Serum sCD21 levels were reduced with age both in patients with SSc and normal controls. Serum sCD21 levels in patients with SSc were significantly decreased compared to those in control subjects. When we divided patients with SSc into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), patients with lcSSc had lower levels of serum sCD21 than those with dcSSc. Moreover, the prevalence of pulmonary fibrosis in the patients with dcSSc inversely correlated with serum sCD21 levels. Our finding may support the notion that B-cell activation is involved in the mechanism for pulmonary fibrosis and skin sclerosis.     

Lipopolysaccharide activation of human endothelial and epithelial cells is mediated by lipopolysaccharide-binding protein and soluble CD14.

Myeloid cell activation by lipopolysaccharides (LPS) involves two proteins, plasma LPS-binding protein (LBP) and cell-membrane CD14. Cell membrane CD14, anchored by a glycerophosphatidylinositol tail, is the cellular receptor for LPS-LBP complexes. Another form of CD14, without the lipid tail, circulates as a soluble plasma protein. In this work we show that soluble CD14 (sCD14) is required for activation of endothelial and epithelial cells by LPS. We propose that LPS-LBP complexes transfer LPS to sCD14, and the LPS-sCD14 complexes then bind to a cellular receptor. Support for this pathway comes from experiments in which LBP and CD14 in normal human serum are blocked by specific antibodies, experiments in which serum is replaced by purified LBP and sCD14, and experiments in which specific binding of [3H]LPS to epithelial cells is quantitated.     

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。     

Biomarkers for evaluation of treatment response in classical Hodgkin lymphoma: comparison of sGalectin‐1, sCD163 and sCD30 with TARC

Soluble Galectin‐1 (sGal‐1, also termed LGALS1), soluble CD163 (sCD163) and soluble CD30 (sCD30) have been reported to be elevated in plasma or serum of patients with classical Hodgkin lymphoma (cHL). We aimed to determine the clinical utility of these biomarkers for evaluation of treatment response compared to thymus and activation regulated chemokine (TARC, also termed CCL17). Plasma or serum samples were prospectively collected among 103 newly diagnosed cHL patients before and after treatment. Levels of sGal‐1, sCD163, sCD30 and TARC were correlated with disease characteristics and clinical treatment response. Elevated plasma levels of sGal‐1, sCD163, sCD30 and TARC were found in 67%, 21%, 91% and 93% of cHL patients respectively. Mean plasma levels of sGal‐1 and sCD30 decreased after treatment but sCD163 did not decrease after treatment. There was no correlation with change of these markers and clinical treatment response in individual patients. TARC levels strongly correlated with disease characteristics and metabolic volume. TARC remained high in 6 out of 7 non‐responsive patients and dramatically decreased in 95 out of 96 responsive patients. In summary, elevated pre‐treatment levels of sGal‐1, sCD163, sCD30 and TARC can be found in patients with cHL. However, only plasma TARC accurately reflects disease activity and correlates with clinical treatment response.     

Enhanced CD21 expression and shedding in chronic lymphatic leukemia: a possible pathomechanism in disease progression

CD21 is a 145-kDa membrane glycoprotein mainly expressed on B cells and follicular dendritic cells, and is involved in B-cell activation, survival and proliferation. CD21 can be cleaved to give soluble CD21 (sCD21), which is constantly shed in healthy persons. We show here that plasma sCD21 levels are higher, while B-cell surface CD21 expression levels are lower in B-cell chronic lymphocytic leukemia (B-CLL) patients, but not in multiple myeloma (MM) patients. High sCD21 levels in the blood are positively correlated to the number of cells with high CD21 surface expression and the relative amount of CD21 expressed on the B cells. B-CLL patients with swollen lymph nodes had higher amounts of CD21 high-expressing B cells, as well as CD21 low-expressing B cells, as compared to B-CLL patients without swollen lymph nodes.     

Soluble CD163 made by monocyte/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after anti-retroviral therapy

CD163, a monocyte- and macrophage-specific scavenger receptor, is shed during activation as soluble CD163 (sCD163). We have previously demonstrated that monocyte expansion from bone marrow with simian immunodeficiency virus (SIV) infection correlated with plasma sCD163, the rate of AIDS progression, and the severity of macrophage-mediated pathogenesis. Here, we examined sCD163 in human immunodeficiency virus (HIV) infection. sCD163 was elevated in the plasma of individuals with chronic HIV infection (>1 year in duration), compared with HIV-seronegative individuals. With effective antiretroviral therapy (ART), sCD163 levels decreased in parallel with HIV RNA levels but did not return to HIV-seronegative levels, suggesting the presence of residual monocyte/macrophage activation even with plasma viral loads below the limit of detection. In individuals with early HIV infection (≤1 year in duration), effective ART resulted in decreased sCD163 levels that were comparable to levels in HIV-seronegative individuals. sCD163 levels in plasma were positively correlated with the percentage of CD14+CD16+ monocytes and activated CD8+HLA-DR+CD38+ T lymphocytes and were inversely correlated with CD163 expression on CD14+CD16+ monocytes. With ART interruption in subjects with early HIV infection, sCD163 and plasma virus levels spiked but rapidly returned to baseline with reinitiation of ART. This study points to the utility of monocyte- and macrophage-derived sCD163 as a marker of HIV activity that links viral replication with monocyte and macrophage activation. These observations underscore the significance of monocyte and macrophage immune responses with HIV pathogenesis.     

Increased serum levels of soluble CD163 in patients with scleroderma

CD163 is a 130-kDa, type I transmembrane protein belonging to group B of the cysteine-rich scavenger receptor family. Expression of CD163 is constitutive and/or induced by some stimuli on circulating monocytes and most tissue macrophages. An approximately 130-kDa soluble form of human CD163 is released from the cell surface by proteolysis after oxidative stress or inflammatory stimuli. Thus, an elevated level of circulating soluble CD163 (sCD163) has been reported in diabetes mellitus, which is one of the oxidative conditions. We have already acknowledged that scleroderma (SSc) is one of the oxidative conditions. Therefore, we conducted the measurement of serum sCD163 in SSc patients. After receiving the informed consents, 56 SSc patients were examined; 20 dermatomyositis patients were used as disease controls and 40 persons were used as healthy controls. Blood samples were collected, and the concentration of serum sCD163 was measured by ELISA (human CD163, R&D Systems). Other parameters in the blood of SSc patients were also examined. Statistical analyses were performed using Mann-Whitney U test, and the relationship between parameters was statistically examined by Spearman's rank test. Serum sCD163 levels were elevated in SSc patients compared with normal controls (p?相似文献   

Plasma, serum, and platelet expression of CD40 ligand in adults with cardiovascular disease

The application of soluble CD40 ligand (sCD40L) as a biomarker has garnered great scientific and clinical interest. However, there are many uncertainties with regard to the biology of sCD40L. Although presumed to be a marker of platelet activation, relative levels in plasma, serum, and platelet expression are unknown, as is the optimal method for its measurement. We measured CD40L from serum, platelet-poor plasma, and platelet surface in adults who had stable cardiovascular disease (CVD) and those who had unstable CVD (n = 40). Plasma sCD40L did not differ significantly between groups. Serum sCD40L was significantly lower (1.4 +/- 1.3 vs 5.2 +/- 3.7 ng/ml, p <0.001) and platelet membrane CD40L expression was higher (1.4 +/- 0.7% vs 0.9 +/- 0.6%, p = 0.03) in unstable compared with stable CVD. When the 2 groups were considered together, there was a significant correlation between plasma and serum sCD40L levels (rho = 0.4, p = 0.02) and negative correlations between plasma (rho = -0.3, p = 0.04) and serum (rho = -0.4, p = 0.01) sCD40L levels with platelet membrane CD40L expression. In unstable CVD, the correlation between sCD40L measurements was poor. Consistent with enhanced platelet activation, there was a positive correlation between platelet aggregation and surface CD40L expression (rho = 0.5, p = 0.02) and between platelet expression of CD40L and P-selectin (rho = 0.4, p = 0.05) in unstable CVD. There was no correlation between CD40L and platelet count or C-reactive protein. Only surface expression of CD40L compared with platelet-derived (plasma) or total (serum) CD40L level proved a reliable marker of platelet function in patients who had stable CVD and those who had unstable CVD. In conclusion, our data demonstrate the complex nature of CD40L and highlight the distinct processes of expression, shedding, and clearance of this ligand in patient populations.     

Decreased levels of sCD21 and sCD23 in blood of patients with systemic-juvenile arthritis, polyarticular-juvenile arthritis, and pauciarticular-juvenile arthritis

A soluble form of CD21 (sCD21) and CD23 (sCD23) is released from the surface of human white blood cells upon shedding of the extracellular domain. sCD21 circulates in a complex with cleavage fragments of C3 and sCD23, which were previously identified as ligands of membrane and soluble CD21. sCD21 seems to be a marker of chronic inflammatory disease. To assess the sCD21 and sCD23 status in patients with subsets of juvenile arthritis (JA), we determined plasma levels sCD21 and sCD23. Plasma sCD21 levels were significantly decreased in all JA subtypes (O-JA P?<?0.0068; P- and S-JA P?<?0.0001) compared to healthy controls. Plasma sCD23 levels were significantly decreased in P-JA and S-JA (both P?<?0.0001), but not in O-JA (P?<?0.3843) in comparison with healthy controls, and data statistically analyzed. Our results suggest that pathological mechanisms relevant to autoimmune disorders interfere with the regulation of both CD21 and CD23 shedding.     

Circulating levels of soluble EMMPRIN (CD147) correlate with levels of soluble glycoprotein VI in human plasma

Abstract

Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147), which binds to the platelet-specific collagen receptor glycoprotein (GP) VI, is expressed in a range of cell types including platelets and leukocytes, and has been implicated in neoplastic disease and atherosclerotic coronary disease. Both CD147 and GPVI can be shed from cell membranes and detected in plasma. However, while the relationship between soluble CD147 (sCD147), soluble GPVI (sGPVI) and standard markers of platelet activation has received little attention, such analysis may help reveal pathways mediating release of sCD147. We investigated the relationship between sCD147 and platelet markers including sGPVI, soluble and platelet-bound CD62P (P-selectin), active αIIbβ3 (assessed by PAC-1 binding) and platelet CD147 in 25 patients with stable angina pectoris (SAP), 13 patients with no coronary artery disease (CAD) and 10 healthy donors. Plasma levels of sCD147 significantly correlated with sGPVI (r?=?0.46, p?=?.004), but did not correlate with any other platelet markers examined. Linear regression analysis identified that sCD147 levels could be predicted by sGPVI levels (β?=?.445, p?=?0.003) and age (β?=?0.304, p?=?0.038), but were independent of potential clinical confounders such as CAD, diabetes and medication usage. As sCD147 strongly correlates with platelet-specific sGPVI, a common platelet source and/or mechanism of release may contribute to sCD147 levels in vivo.     

Soluble CD4 concentrations predict relapse of post-partum thyroiditis

Post-partum thyroiditis (PPT) is a common autoimmune thyroid disorder which results in significant morbidity at a critical time of a woman's life. The presence of anti-thyroglobulin (anti-TG) and, more so, anti-thryroperoxidase (anti-TPO) antibodies in the first trimester of pregnancy has been reported to forecast subsequent PPT. Despite their predictive value, these tests lack in specificity. We have sought to find an alternative that is more specific and, ideally, which could be tested immediately proximate to the event. We have taken advantage of the high recurrence rate of PPT in subsequent pregnancies to perform a prospective study of serum soluble CD4 (sCD4) and CD8 (sCD8) levels in 22 pregnant women who had at least one previous episode of PPT. This group was matched with 21 pregnant women of comparable age with no evidence of thyroid disease. Both groups of women were sampled in each of the three trimesters of pregnancy, 1 month, 3 months and 6 months post-partum for sCD4, sCD8, thyroid function parameters and antibodies. Twelve of the 22 women with previous PPT had recurrent disease; they were more likely to be cigarette smokers and to have a family history of autoimmune disorders (p<0.05, for both) than those who did not. Half of these women had high anti-TG or anti-TPO each in the first trimester compared to none among those without recurrent PPT and 2/21 controls. Serum sCD8 levels showed no changes over the observation points among the two PPT patient subsets and were comparable to those of the controls. By contrast, serum sCD4 concentrations showed divergent changes in the group with recurrent PPT in the course of pregnancy and postpartum period compared to those without disease recurrence and controls: sCD4 failed to show the physiological fall in the third trimester of pregnancy [19.0+/-1.7 (+/-SD) U/ml vs 15.6+/-2.3 U/ml in controls, NS]. This trend was continued into the first month post-partum when sCD4 levels were clearly higher than in controls (22.1+/-2.6 U/ml compared to 17.9+/-1.9 U/ml in controls, p<0.001) and well before the episode of PPT. An sCD4 serum level outside the 95% reference range at 1 month post-partum (9/12 in recurrent PPT, 1/21 in controls) yields a relative risk of 6.9 (chi2=14.67, p<0.001) compared to 3.3 for first trimester thyroid antibody positivity (p=0.029). In summary, we describe a reliable test for forecasting PPT that can be obtained immediately proximate to the possible event. If our findings are verified in larger studies, the measurement of serum sCD4 concentration drawn in the first month post-partum may prove an ideal test for population screening for impending PPT.     

早期调脂干预对急性心肌梗死患者炎症因子的影响

目的观察早期较大剂量阿托伐他汀治疗急性心肌梗死(AMI)3d后患者血清可溶性CD40L(sCD40L)、P-选择素及可溶性血管粘附分子水平的变化,以探讨早期调脂干预对AMI斑块稳定、抑制炎症反应的作用。方法选取43例AMI患者随机分为常规治疗组(无服用任何调脂药物,21例)和阿托伐他汀组(立普妥20mg,qd,22例),测定治疗前后sCD40L、P-选择素、可溶性细胞间粘附分子-1(sICAM-1)和可溶性血管细胞间粘附分子-1(sV-CAM-1)的水平。结果两组治疗前后血脂水平变化无显著性差异。阿托伐他汀组治疗后血清sCD40L、P-选择素、sICAM-1分别下降35％、41％、30％,明显低于治疗前水平(P<0.05),sVCAM-1稍下降,但无统计学意义;在常规治疗组治疗前后上述指标均无明显变化。在阿托伐他汀组sCD40L、P-选择素、sICAM-1的降低与总胆固醇(TC)(分别为r=0.08,P=0.56;r=0.16,P=0.34;r=0.12,P=0.41),低密度脂蛋白胆固醇(LDL-C)(分别为r=0.09,P=0.88;r=0.11,P=0.46;r=0.18,P=0.77)的下降百分数之间无相关关系。结论在AMI的早期使用阿托伐他汀治疗3d,可明显降低血清炎症因子水平,可能有利于动脉粥样硬化斑块的稳定。     

Serum levels of CD8 antigen and soluble interleukin 2 receptors in patients with B cell chronic lymphocytic leukemia

We assayed the plasma levels of CD8 antigen (CD8Ag) and soluble interleukin 2 receptor (sIL-2R) in 34 subjects with B cell chronic lymphocytic leukemia (B-CLL) and in 15 controls using an immunoenzymatic method. The results showed higher average levels of soluble CD8 (sCD8) and sIL-2R in the leukemic patients compared to the controls (sCD8 = 860 vs. 306 U/ml; sIL-2R = 4,131 vs. 311 U/ml). The two antigen levels were significantly higher in patients with progressive disease than in those with indolent disease, and they also correlated with Rai's stage. sIL-2R levels correlated with lymphocyte count (p less than 0.001), while there was no correlation between sCD8 levels and total number of lymphocytes. These results seem to show that the measurement of serum levels of CD8Ag and sIL-2R may be a useful tool in the prognostic evaluation of patients with B-CLL.     

Serum levels of soluble CD30 in autologous peripheral blood stem cell transplantation

High-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important method of treatment for hematological and solid tumors. We examined levels of interleukin(IL)-4, interferon (IFN)γ, soluble (s) CD30, and sIL-2 receptor (R) before and after autologous PBSCT, and compared findings for PBSCT with those for bone marrow transplantation (BMT). We found significantly higher IL-4 levels 1 and 3 weeks after PBSCT than before PBSCT, while IFNγ levels remained almost unchanged after PBSCT. IFNγ levels were increased 3 weeks after BMT, although no increase in IL-4 level was observed. The serum sCD30 level was significantly higher 3 weeks after PBSCT, but not following BMT. For 34 samples on days 0 and 21 from 17 patients undergoing PBSCT, a strong correlation was observed between sCD30 and sIL-2R levels (r = 0.43, P < 0.01). However, no significant correlation between sCD30 and sIL-2R levels was found for BMT patients. These findings suggest that sCD30 is a useful marker for evaluating immunological activity following autologous PBSCT, and that the immunological conditions after autologous PBSCT may be associated with helper-T-cell-2-type immune responses. Received: 31 May 1999 / Accepted: 20 September 1999     

Associations of Soluble CD14 and Endotoxin with Mortality,Cardiovascular Disease,and Progression of Kidney Disease among Patients with CKD

Background and objectives

CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher levels of soluble CD14 (sCD14) are associated with overall mortality in hemodialysis patients. The influence of kidney function on plasma sCD14 levels and its relationship with adverse outcomes in patients with CKD not yet on dialysis is unknown. This study examines the associations between plasma levels of sCD14 and endotoxin with adverse outcomes in patients with CKD.

Design, setting, participants, & measurements

We measured plasma levels of sCD14 and endotoxin in 495 Leuven Mild-to-Moderate CKD Study participants. Mild-to-moderate CKD was defined as presence of kidney damage or eGFR<60 ml/min per 1.73 m² for ≥3 months, with exclusion of patients on RRT. Study participants were enrolled between November 2005 and September 2006.

Results

Plasma sCD14 was negatively associated with eGFR (ρ=–0.34, P<0.001). During a median follow-up of 54 (interquartile range, 23–58) months, 53 patients died. Plasma sCD14 was predictive of mortality, even after adjustment for renal function, Framingham risk factors, markers of mineral bone metabolism, and nutritional and inflammatory parameters (hazard ratio [HR] per SD higher of 1.90; 95% confidence interval [95% CI],1.32 to 2.74; P<0.001). After adjustment for the same risk factors, plasma sCD14 was also a predictor of cardiovascular disease (HR, 1.30; 95% CI, 1.00 to 1.69; P=0.05). Although plasma sCD14 was associated with progression of CKD, defined as reaching ESRD or doubling of serum creatinine in models adjusted for CKD-specific risk factors (HR, 1.24; 95% CI, 1.01 to 1.52; P=0.04), significance was lost when adjusted for proteinuria (HR, 1.19; 95% CI, 0.96 to 1.48; P=0.11). There was neither correlation between plasma endotoxin and sCD14 (ρ=–0.06, P=0.20) nor was endotoxin independently associated with adverse outcome during follow-up.

Conclusions

Plasma sCD14 is elevated in patients with decreased kidney function and associated with mortality and cardiovascular disease in patients with CKD not yet on dialysis.     

Correlation of CD95 and soluble CD95 expression with acute rejection status of liver transplantation

AIM: To analyze the expression levels of soluble form of CD95, CD95 ligand (sCD95 and SCD95L, respectively) in plasma and CD95 expression on CD3+cells in liver-transplanted recipients with acute rejection (AR). METHODS: Peripheral blood mohonuclear cells (PBMCs) were isolated from 30 clinically liver transplanted recipients. CD95 expression on CD3+ cells was quantitatively measured by two-color fluorescence activated cell sorter (FACS) analysis. Lymphocyte surface phenotypes of CD4, CD8, CD16 and CD56 were determined by flow cytometry. Plasma levels of sCD95 and SCD95L were detected by Enzyme Linked-Immuno-Sorbent Assay (ELISA). The results were compared with that from normal healthy volunteers (n=15 individuals). RESULTS: FACS analysis showed that CD95 expression on CD3+ T cells was significantly increased in liver transplanted recipients with AR compared to that in stable recipients without rejection and infection or healthy individuals who did not undergo transplantation (18 676.93±11 588.34/molecule, 6 848.20±1 712.96/molecule, 6 418.01±2 001.95/molecule, respectively, P<0.01). Whereas no significant difference was seen between liver-transplanted stable recipients and healthy individuals. Furthermore, no significant differences were detected between each group with CD4/CD8 ratio or the percentage of CD16+56+cells. Plasma levels of sCD95 were significantly higher in transplanted recipients with AR compared to that in stable recipients or healthy individuals (391.88±196.00, 201.37±30.30, 148.83±58.25 pg/mL, respectively, P<0.01). In contrast, the plasma levels of sCD95L in liver-transplanted recipients were not significantly different from that in healthy individuals. CONCLUSION: The present results indicate that the increased CD95 expression on CD3+cells and the increased levels of sCD95 in plasma may modify the immunological situation of the recipients after transplantation or represent the ongoing graft rejection.     

Serum soluble CD8 molecule is a marker of CD8 T-cell activation in HIV-1 disease

To characterize CD8 T-cell activation during HIV-1 infection we measured serum soluble CD8 (sCD8) levels longitudinally in seroconverters and in individuals with established HIV infection who were in different stages of illness. CD8 T-cell activation occurs very early in HIV infection. Serum sCD8 levels were elevated in 91.5% of the first seropositive samples in seroconverters. Furthermore, CD8 T-cell activation persists throughout HIV infection. sCD8 predicted the occurrence of AIDS in HIV-seropositive individuals and so the addition of serum sCD8 levels to CD4 T-cell measurements increased the power in predicting the onset of AIDS. The serum level of sCD8 was particularly relevant to the prediction of subsequent CD4 T-cell fall relatively early in infection, for example, in the 3 years after seroconversion. However, later in HIV infection, for example within 2 years prior to development of AIDS, sCD8 levels were less predictive. sCD8 correlated with levels of beta 2-microglobulin and neopterin, which reflect activation of cell types other than CD8. Thus, serum sCD8 level can be a useful marker of specific CD8 T-cell activation, and is an independent predictor of prognosis in HIV infection.     

Soluble CD163 in patients with liver diseases: very high levels of soluble CD163 in patients with fulminant hepatic failure

Background The levels of several cytokines and chemokines are elevated in various liver diseases, especially in fulminant hepatic failure (FHF). Activated macrophages may have a role in the production of these immune modulators. CD163 is a member of a scavenger receptor family and is expressed mainly on activated macrophages, and a soluble form of CD163 (sCD163) is released from activated macrophages. The aim of this study was to assess sCD163 levels in patients with FHF and to evaluate their clinical significance.Methods The levels of sCD163 in the sera were measured in 21 patients with FHF, 17 patients with acute hepatitis (AH), 22 patients with chronic hepatitis (CH), and 14 normal healthy controls (NC), by an enzyme-linked immunosorbent assay. The levels of sCD163 were observed serially in patients with FHF and AH.Results The levels of sCD163 in the sera from patients with FHF were significantly higher than those in patients with AH and CH and the NC group (P < 0.0001). There was a good correlation between serum levels of sCD163 and prothrombin time (r = –0.677; P < 0.0001). A kinetic study revealed that the levels of sCD163 decreased in patients with AH and in survivors of FHF, whereas the levels of sCD163 progressively increased in nonsurvivors of FHF.Conclusions This study shows that the products of activated macrophages may be involved in the pathogenesis of FHF. This study also inspires optimism that sCD163 may possess prognostic importance in FHF.