The role of the CD95, CD38 and TGFbeta1 during active human cytomegalovirus infection in liver transplantation

AIM: Human cytomegalovirus (HCMV) has highly evolved mechanisms for avoiding detection by the host immune system. The aim of this study was to analyze the expression levels of TGFbeta1, soluble form of CD95, CD95 ligand (sCD95 and sCD95L, respectively) in plasma and CD95 expression on CD3(+) cells, CD38 expression on CD8(+) cells in liver transplanted recipients with active HCMV infection. METHODS: Blood samples were collected from 15 liver transplanted recipients with active HCMV infection and 15 recipients without HCMV infection. CD95 expression on CD3(+) cells and CD38 expression on CD8(+) cells were quantitatively detected with two-color fluorescence activated cell sorter (FACS) analysis. Lymphocyte surface phenotypes of CD4 and CD8 were detected with FACS analysis. Plasma sCD95, sCD95L and TGFbeta1 levels were determined with enzyme linked-immuno-sorbent assay (ELISA). The results were compared with that from 15 healthy individuals. RESULTS: CD95 expression on CD3(+) T-cells and CD38 expression on CD8(+) cells were significantly increased in active HCMV infection group compared with that in stable group or healthy group (P<0.01). No significant difference was seen between stable group and healthy group (P>0.05). The percentages of CD4(+) T-cell and CD4/CD8 ratio in active HCMV infection group were significantly lower than the values in stable group and healthy group (P<0.05). Plasma levels of TGFbeta1 and sCD95 were significantly increased in active HCMV infection group compared to stable group and healthy group (P<0.05). In contrast, plasma levels of sCD95L in healthy group were not significantly different from that expressed in active HCMV infection group and stable group (P>0.05). CONCLUSION: HCMV suppress proliferation of activated T cells by apoptosis and by releasing immunosuppressive cytokine TGFbeta1. This may provide an important clue to a better understanding of the pathogenesis in liver transplanted recipients with active HCMV infection.     

Distinctive response of thyroid-infiltrating mononuclear cells to B cell activation through CD40 and interleukin-4 in Graves' patients

The possible role of abnormal T cell-dependent B-cell activation in Graves' disease was investigated by comparing lymphocyte subset distribution and the production of soluble CD8 (sCD8), sCD23, IL-10 and IL-12 by peripheral blood cells (PBMC) and thyroid-infiltrating lymphocytes (TL) in vitro. In TL, the percentage of CD8(+) cells was slightly higher and the sCD8 concentration was significantly higher than in PBMC. The ratio CD23(+) cells to CD20(+) cells (activated B/pan B cells) was increased in TL compared to PBMC from Graves' or normal controls, although the percentage of CD20(+) cells was decreased. Compared to PBMC in Graves' disease, the relative ratio of IL-10 to IL-12 release (IL-10/IL-12) by unstimulated TL was increased, despite a lack of significant difference between PBMC and TL in mean values for either IL-10 or IL-12 secretion. Incubating PBMC with a combination of anti-CD40 monoclonal antibodies and interleukin-4 (IL-4) resulted in B cell activation, reflected in an increase in the sCD23 level in both controls and Graves' patients, but especially prominent in the latter. Stimulation with anti-CD40 antibody and IL-4 also decreased the percentage of CD8(+) cells in PBMC but not TL from both Graves' disease and normal controls, and the percentage of CD8(+) cells in TL was higher than PBMC after the stimulation. The sCD23 concentration in TL was decreased compared to PBMC both in patients with Graves' disease and normal controls. However, in contrast to the increased responses observed in Graves' PBMC or normal controls after stimulation, sCD23 levels remained the same in stimulated TL from Graves' patients. This combination of B cell stimulants increased production of IL-10 in PBMC but not in TL obtained from patients with Graves' disease, and the increased IL-10/IL-12 ratio declined to a value no different from that in PBMC group after stimulation. Thus, T cell-dependent B-cell activation via a CD40 pathway may cause a shift in the Th(1)/Th(2) balance to Th(2) dominance in Graves' disease, while increased CD8(+) cells in TL may suppress sCD23 production and IL-10-producing Th(2) cells.     

Plasma levels of soluble CD36, platelet activation, inflammation, and oxidative stress are increased in type 2 diabetic patients

Inflammation, oxidative stress, and platelet activation are involved in type 2 diabetes and its complications. Soluble CD36 (sCD36) has been proposed to early identify diabetics at risk of accelerated atherothrombosis. We aimed at characterizing the platelet contribution to sCD36 in diabetes, by correlating its concentration with the extent of platelet-mediated inflammation and in vivo lipid peroxidation and investigating the effects of low-dose aspirin on these processes. A cross-sectional comparison of sCD36, soluble CD40L (sCD40L) reflecting platelet-mediated inflammation, urinary 11-dehydro-TxB(2), and 8-iso-PGF(2α), in vivo markers of platelet activation and lipid peroxidation, was performed among 200 diabetic patients (94 of them on aspirin 100mg/day) and 47 healthy controls. sCD36 levels (median [IQR]: 0.72 [0.31-1.47] vs 0.26 [0.2-0.37], P=0.003) and urinary 11-dehydro-TxB(2) levels (666 [293-1336] vs 279 [160-396], P≤0.0001) were significantly higher in diabetic patients not on aspirin (n=106) than in healthy subjects. These variables were significantly lower in aspirin-treated diabetics than untreated patients (P<0.0001). Among patients not on aspirin, those with long-standing diabetes (>1 year) had significantly higher sCD36 levels in comparison to patients with diabetes duration <1 year (1.01 [0.62-1.86] vs 0.44 [0.22-1.21], P=0.001). sCD36 linearly correlated with sCD40L (rho=0.447; P=0.0001). On multiple regression analysis, 11-dehydro-TxB(2) (β=0.360; SEM=0.0001, P=0.001), 8-iso-PGF(2α) (β=0.469; SEM=0.0001, P<0.0001), and diabetes duration (β=0.244; SEM=0.207, P=0.017) independently predicted sCD36 levels. sCD36, platelet activation, inflammation, and oxidative stress are increased in type 2 diabetes. Future studies are needed to elucidate if the incomplete down-regulation of sCD36 by low-dose aspirin implies that sCD36 may be derived from tissues other than platelets or if additional antiplatelet strategies in diabetes are necessary to interrupt CD36-dependent platelet activation.     

Increased Bone Marrow (BM) Plasma Level of Soluble CD30 and Correlations with BM Plasma Level of Interferon (IFN)-γ, CD4/CD8 T-Cell Ratio and Disease Severity in Aplastic Anemia

Idiopathic aplastic anemia (AA) is an immune-mediated bone marrow failure syndrome. Immune abnormalities such as decreased lymphocyte counts, inverted CD4/CD8 T-cell ratio and increased IFN-γ-producing T cells have been found in AA. CD30, a surface protein belonging to the tumor necrosis factor receptor family and releasing from cell surface as a soluble form (sCD30) after activation, marks a subset of activated T cells secreting IFN-γ when exposed to allogeneic antigens. Our study found elevated BM plasma levels of sCD30 in patients with SAA, which were closely correlated with disease severity, including absolute lymphocyte count (ALC) and absolute netrophil count (ANC). We also noted that sCD30 levels were positively correlated with plasma IFN-γ levels and CD4/CD8 T-cell ratio in patients with SAA. In order to explain these phenomena, we stimulated T cells with alloantigen in vitro and found that CD30⁺ T cells were the major source of IFN-γ, and induced CD30⁺ T cells from patients with SAA produced significantly more IFN-γ than that from healthy individuals. In addition, increased proportion of CD8⁺ T cells in AA showed enhanced allogeneic response by the fact that they expressed more CD30 during allogeneic stimulation. sCD30 levels decreased in patients responded to immunosuppressive therapy. In conclusion, elevated BM plasma levels of sCD30 reflected the enhanced CD30⁺ T cell-mediated immune response in SAA. CD30 as a molecular marker that transiently expresses on IFN-γ-producing T cells, may participate in mediating bone marrow failure in AA, which also can facilitate our understanding of AA pathogenesis to identify new therapeutic targets.     

Serum Levels of Soluble IL-2R, CD4 and CD8 in Chronic Active HCV Positive Hepatitis

The aim of the present study was to compare serum levels of soluble forms of interleukin-2 receptor, CD4 and CD8, released by lymphocytes during activation ofthe immune system, in patients with histologically verified chronic active hepatitis associated to hepatitis C virus infection, with those in healthy subjects. Significantly higher levels of soluble IL-2R and soluble CD8 were found in patients with chronic active hepatitis compared with controls. In contrast no difference was found for soluble CD4 values in the two groups. No correlations were found for both sIL-2R and sCD8 and these two molecules with other parameters of liver function. These results indicate that in these patients there is a general activation of the immune system, but the lack of correlation with parameters of liver function strengthens the suggestion that this activation does not play a role in the pathogenesis of chronic type C hepatitis.     

Soluble interleukin-2 receptor and soluble CD8 molecules in cerebrospinal fluid and serum of patients with multiple sclerosis.

The purpose of this study was to analyse soluble interleukin-2 receptor (sIL-2R) and soluble CD8 (sCD8) molecules in the cerebrospinal fluid (CSF) and serum of 18 patients with definite multiple sclerosis (MS) and of 16 with noninflammatory neurologic diseases (NIND). All MS patients suffered from an exacerbation of the relapsing-remitting form of the disease within one month before examination. The mean serum levels of sIL-2R and sCD8 in the MS patients were not significantly different from those of NIND patients. Only one patient with MS had detectable sIL-2R in the CSF. CSF sCD8 was detectable in 10 of 18 MS patients and in 1 of 16 NIND patients. Our data indicate that the CSF and serum sIL-2R concentrations do not correlate with the disease activity. Conversely, increased levels of sCD8 only in the CSF of MS patients support the hypothesis of an intrathecal activation of CD8+ cells in MS. We think that CSF sCD8 can be a useful marker for the presence of activated T cells in the central nervous system.     

Soluble CD23 in Human Immunodeficiency Virus Type 1 Infected Patients

The level of sCD23 produced in the course of human immunodeficiency virus (HIV) infection was measured in patients grouped according to the Centers for Disease Control by using an immunoradiometric assay. Soluble CD23 was evaluated in supernatants of peripheral blood mononuclear cell (PBMC) (10⁶ cells/ml) stimulated by phytohemagglutinin (PHA). Compared with healthy controls (m±S.D. = 1.0 ±0.34 U/ml, n = 7), higher values were observed in some of the patients of group II (asymptomatic) (m±S.D. = 2±1.33, n = 9) and some of the patients of group IV (AIDS) (m±S.D. = 1.3 ±1.40, n = 8). Those results prompted us to compare the plasma levels of sCD23 in group II and group IV HIV-infected patients and in healthy individuals. Soluble CD23 plasma levels in healthy patients (n = 42) ranged from 0 to 1.5 U/ml (m±S.D. = 0.9±0.33), in group II patients (n = 17) from 0 to 3 U/ml (m±S.D. = 0.92±0.83) and in group IV patients (n =73) from 0 to 2.9 U/ml (m±S.D. = 1.15±0.71). The differences between the patients and the healthy individuals were not statistically significant but individual sCD23 values higher than 2 U/ml were obtained in 6% of the group II patients and 16.7% of the group IV patients. Increased values of sCD23 were obtained in plasma from patients with secondary infectious diseases (groups IV-C1 and IV-C2) and from patients without secondary infectious diseases (group II, group IV-A and group IV-B). Elevated values of sCD23 were detected even in patients with low counts of CD4⁺ T cells and CD8⁺ T cells in their peripheral blood. sCD23 has numerous activities including control of IgE synthesis and cytokine-like properties. Our results show a disarray of sCD23 in HIV-infected patients which could be involved in drug reactions, allergic manifestations and the IgE-level increase. Further investigations should attempt to define the role of sCD23 in clinical manifestations of HIV infection.     

Serum levels of soluble IL-2R, CD4 and CD8 in bronChial asthma

The aim of the present study was to compare serum levels of soluble forms of interleukin-2 receptor, CD4 and CD8, released by lymphocytes during activation of the immune system, in patients with allergic bronchial asthma, with those in healthy subjects. Significantly higher levels of soluble IL-2R and soluble CD4 were found in patients with asthma compared with the control group. In contrast, lower levels of soluble CD8 values were found in patients with asthma compared to the control group. Significant correlations were found for both sIL-2R and sCD4 and these two molecules, with lung function measured as bronchial responsiveness to inhaled methacholine. These results strengthen previous suggestions that in allergic bronchial asthma, activation of T cells plays a significant role in the disease pathogenesis.     

Differential levels of soluble endoglin (CD105) in myeloid malignancies

Angiogenesis contributes to disease progression in solid and hematopoietic malignancies, and endoglin (CD105), a component of the transforming growth factor (TGF)-beta receptor complex, is a powerful marker of neovascularization. Elevated amounts of soluble CD105 (sCD105) have been recently identified in selected solid tumors but no data are available on sCD105 in hematopoietic malignancies. Therefore, levels of sCD105 were investigated in sera of patients with acute myeloid leukemia (AML) (n = 10) or chronic myeloproliferative disorders (CMD) (n = 28), and correlated with those of soluble TGF-beta(1) (sTGF-beta(1)). Dot blot assay detected higher amounts of sCD105 (P < 0.05) both in AML (4.34 +/- 2.62 OD/mm(2)) and in CMD (3.71 +/- 2.09 OD/mm(2)) patients than in healthy subjects (n = 14, 2.38 +/- 1.18 OD/mm(2)). Instead, enzyme-linked immunosorbent assay (ELISA) identified (P < 0.05) lower and higher levels of sTGF-beta(1) in AML (32,017 +/- 1,900 pg/ml) and CMD (60,700 +/- 19,200 pg/ml) patients, respectively, compared to healthy individuals (n = 11, 47,173 +/- 5,443 pg/ml). In essential thrombocythemia (ET) patients with thrombotic episodes, levels of sCD105 were lower (P < 0.05) compared to patients without thrombotic complications, and inversely correlated with those of sTGF-beta(1) (r = 0.94). Conversely, amounts of sCD105 directly correlated with levels of sTGF-beta(1) (r = 0.74) in ET patients without thrombotic events. Our results show that high levels of sCD105 are present in myeloid malignancies that are characterized by a high cellular proliferation rate, and suggest that an altered balance between sCD105 and sTGF-beta(1) might favor disease progression and clinical complications.     

CD64指数、sCD14、sCD163与胸腔镜肺癌根治术后并发重症肺部感染的关系研究

摘要 目的：探讨CD64指数、可溶性白细胞分化抗原14（sCD14）、可溶性白细胞分化抗原163（sCD163）与胸腔镜肺癌根治术后并发重症肺部感染的关系。方法：选择2020年1月至2023年1月南通市肿瘤医院收治的行胸腔镜肺癌根治术治疗的非小细胞肺癌（NSCLC）患者共415例。根据术后是否并发重症肺部感染将患者分为感染组（21例）和未感染组（394例）。检测外周血CD64指数和血清sCD14、sCD163水平。多因素Logistic回归分析影响胸腔镜肺癌根治术后并发重症肺部感染的因素。受试者工作特征（ROC）曲线分析CD64指数、sCD14、sCD163预测胸腔镜肺癌根治术后并发重症肺部感染的价值。结果：感染组外周血CD64指数、血清sCD14、sCD163水平高于未感染组（P＜0.05）。多因素Logistic回归分析显示高CD64指数、sCD14、sCD163、降钙素原（PCT）是胸腔镜肺癌根治术后并发重症肺部感染的危险因素（P＜0.05）,高呼气峰值流量（PEF）是保护因素（P＜0.05）。CD64指数、sCD14、sCD163、PCT预测胸腔镜肺癌根治术后并发重症肺部感染的曲线下面积为0.834、0.815、0.842、0.784,联合预测曲线下面积为0.928,高于单独预测。结论：血清CD64指数、sCD14、sCD163、PCT水平升高是胸腔镜肺癌根治术后并发重症肺部感染的危险因素。联合CD64指数、sCD14、sCD163、PCT可较好地预测术后重症肺部感染的风险。     

Characterization of CD200 Ectodomain Shedding

We have previously reported the existence of a soluble form of CD200 (sCD200) in human plasma, and found sCD200 to be elevated in the plasma of Chronic Lymphocytic Leukemia (CLL) patients. CLL cells release CD200 at a constitutive level, which could be attenuated partially by ADAM28 silencing. In this study, we further explored mechanisms of CD200 shedding beyond that of ADAM28, and performed biochemical analysis of sCD200 using materials derived from purified CLL cells and Hek293 cells stably transfected with CD200, and antibodies generated specifically against either the extracellular or cytoplasmic regions of CD200. CD200 shedding was enhanced by PMA stimulation, and the loss of cell surface CD200 could be monitored as a reduction in CD200 cell surface expression by flow cytometry, in parallel with an increase in the detection of sCD200 in the supernatant. Western blot analyses and functional studies using CD200R1 expressing Hek293 cells showed that the shed CD200 detected in CLL and Hek293-hCD200 supernatants lacked the cytoplasmic domain of CD200 but retained the functional extracellular domain required for binding to, and phosphorylation of, CD200R. These data confirms that a functionally active CD200 extracellular moiety can be cleaved from the surface of CD200 expressing cells following ectodomain shedding.     

Serum levels of soluble CD30 in adult patients affected by atopic dermatitis and its relation to age,duration of disease and Scoring Atopic Dermatitis index

The value of CD30 and the soluble circulating fragment of CD30 (sCD30) for atopic dermatitis (AD) remains unclear. In particular, little is known about the effects of age, duration of disease and Scoring Atopic Dermatitis index (SCORAD) on the levels of serum sCD30 in patients affected by AD. In the present study, we have analysed serum sCD30 levels of adult patients affected by AD. The study's population includes 18 non-smoking outpatients, with a diagnosis of AD. As a control group we studied 18 non-atopic subjects from laboratory staff, matched for sex and age. These subjects had no history of AD, urticaria or seasonal or perennial rhinitis or asthma, and had negative skin prick test to a panel of allergens. The sCD30 serum levels were clearly higher in patients affected by AD (14.2+/-9.0 IU/ml) than in healthy subjects (1.2+/-0.8 IU/ml) (p<0.001). No differences were observed between males and females affected by atopic dermatitis, regarding age, duration of disease and SCORAD. Significant correlations were found between serum levels of sCD30 levels and age (r=-0.55; 95% confidence interval (CI) for r (Fisher's z transformed)=-0.81 to -0.12; p=0.01), duration of the disease (months) (r=-0.64; 95% CI for r (Fisher's z transformed)=-0.85 to -0.24; p=0.004) and SCORAD (r=-0.74; 95% CI for r (Fisher's z transformed)=-0.89 to -0.42; p=0.004). As demonstrated by the close correlation with age, duration of disease and SCORAD, serum levels of sCD30 appear to be an additional marker for the follow-up of AD.     

CD14 gene promoter polymorphism in different clinical forms of tuberculosis

Mycobacterium tuberculosis interacts with monocyte-macrophages through cell surface molecules including CD14. A soluble form of CD14 (sCD14) exists in human serum, and higher amounts of it are found in tuberculosis. A polymorphism on CD14 gene promoter was associated with increased sCD14 levels in some diseases. To evaluate whether this polymorphism associates with tuberculosis, its clinical forms, and increased sCD14, genotype/allele frequencies in tuberculosis patients were compared with the controls. Results confirmed increased levels of sCD14 in patients with tuberculosis, and those with miliary tuberculosis had the highest levels. sCD14 decreased to normal levels after anti-tuberculosis treatment. No association was found between the CD14 polymorphism and tuberculosis or sCD14 levels. Results suggest that sCD14 may be involved in anti-tuberculosis immune response, but its increase is a consequence of infection rather than a predisposed genetic trait. Measuring sCD14 in tuberculosis may help monitor anti-tuberculosis treatment.     

Soluble CD40 Ligand in Aspirin-Treated Patients Undergoing Cardiac Catheterization

Plasma soluble CD40 ligand (sCD40L) is mainly generated by cleavage of CD40L from the surface of activated platelets, and therefore considered a platelet activation marker. Although the predictive value of sCD40L for ischemic events has been demonstrated in patients with acute coronary syndromes (ACS), studies on the association of sCD40L with cardiovascular outcomes in lower risk populations yielded heterogeneous results. We therefore sought to investigate factors influencing sCD40L levels, and the predictive value of sCD40L for long-term ischemic events in unselected, aspirin-treated patients undergoing cardiac catheterization. sCD40L was determined by a commercially available enzyme-linked immunosorbent assay in 682 consecutive patients undergoing cardiac catheterization. Two-year follow-up data were obtained from 562 patients. Dual antiplatelet therapy with aspirin and clopidogrel was associated with significantly lower levels of sCD40L and lower platelet surface expressions of P-selectin and activated GPIIb/IIIa compared to aspirin monotherapy (all p≤0.01). Hypertension was linked to lower plasma concentrations of sCD40L, whereas female sex, increasing high-sensitivity C-reactive protein, and hematocrit were associated with higher sCD40L concentrations (all p<0.05). sCD40L levels were similar in patients without and with the primary endpoint in the overall study population (p = 0.4). Likewise, sCD40L levels did not differ significantly between patients without and with the secondary endpoints (both p≥0.4). Similar results were obtained when only patients with angiographically-proven coronary artery disease (n = 459), stent implantation (n = 205) or ACS (n = 125) were analyzed. The adjustment for differences in patient characteristics by multivariate regression analyses did not change the results. ROC curve analyses did not reveal cut-off values for sCD40L for the prediction of the primary or secondary endpoints. In conclusion, plasma sCD40L levels are reduced by antiplatelet therapy with clopidogrel, but not associated with long-term ischemic outcomes in unselected consecutive aspirin-treated patients undergoing cardiac catheterization.     

CD14 is an acute-phase protein

The origin of soluble CD14 (sCD14) in the circulation is uncertain. To examine whether CD14 could be an acute-phase protein (APP), the levels of sCD14, IL-6, and C-reactive protein were determined by ELISA in serum and synovial fluid (SF) of patients with various arthropathies, and the regulation of CD14 synthesis was examined in liver cells. In patients with crystal-mediated or immunologically mediated arthritis (rheumatoid arthritis), serum levels of sCD14 were higher than or similar to those found in infection-mediated arthritis (reactive arthritis), precluding a relation with bacteria exposure. Levels of sCD14 were similar in SF and serum, and did not correlate with the number of SF leukocytes, excluding an important source from leukocyte membrane-bound CD14, by protease-mediated shedding. In contrast, serum levels of sCD14 in patients correlated with those of C-reactive protein, a classical APP, and IL-6, a cytokine known to regulate the synthesis of APP in the liver. Serum levels of sCD14 also correlated with disease activity in rheumatoid arthritis and reactive arthritis patients. IL-6 stimulated the production of CD14 by HepG2 hepatoma cells. By real-time PCR, the inducibility of CD14 by IL-6 was also observed at the mRNA level both in HepG2 cells and human primary hepatocytes. These in vitro results were confirmed by in vivo studies in IL-6(-/-) mice injected with turpentine, an experimental model of acute-phase response. Liver levels of CD14 mRNA increased in IL-6(+/+), but not in IL-6(-/-) mice. These results indicate that sCD14 can be considered as a type 2 APP.     

Lymphocyte activation in patients with acute myeloid leukaemia Evidence for the presence of myeloblast antigen?

Summary A group of 27 patients with acute myeloid leukaemia (AML), 15 with acitve disease and 12 in complete remission, were investigated for evidence of T cell activation. The parameters of T cell activation measured were the serum levels of soluble interleukin-2 receptor (sIL-2R), soluble CD4 (sCD4) and soluble CD8 (sCD8) molecules and the proportions of T cells expressing the cytotoxicity-linked cytoplasmic serine esterase. All patients studied with active disease had elevated sIL-2R and sCD8 molecules and an elevated proportion of T cells expressing serine esterase. Patients studied in complete remission also had elevated sIL-2R, sCD8 and serineesterase-positive T cells, but values were lower than those studied in active disease. These patients were all studied in the absence of any ongoing or recent infection or exposure to homologous blood products, either of which could potentially affect these parameters. In the absence of any obvious alternative cause, we suggest these data indicate that AML leukaemia blast cells may be immunogenic and lead to the activation of cytotoxic T cells.     

系统性红斑狼疮患者血清中CD83与自身抗体的表达及其相互关系

目的：检测系统性红斑狼疮（systemic lupus erythematosus,SLE）患者血清中CD83（soluble CD 83,sCD 83）和多种自身抗体的表达水平,并探讨其相互关系。方法：ELISA检测患者可溶性CD 83和AnuA的表达,应用间接免疫荧光的方法检测抗cmDNA抗体,应用乳凝法检测血清中的DNP,采用胶体金标记和快速膜渗滤技术测定血清中的抗dsDNA抗体。结果：对照组患者血清中可溶性CD 83的表达为（0.26±0.10）ng/ml,实验组患者血清中可溶性CD 83的表达为（5.56±0.72）ng/ml。与对照组相比,实验组患者血清中可溶性CD 83的平均浓度明显升高。在抗dsDNA抗体阴性的51例系统性红斑狼疮患者中AnuA的阳性率明显高于抗DNP抗体和抗cmDNA抗体,同样在抗DNP抗体阴性的58例系统性红斑狼疮患者中AnuA的阳性率明显高于dsDNA抗体和抗cmDNA抗体。系统性红斑狼疮患者中可溶性CD83的水平（〈2.68 ng/ml）与各种自身抗体（抗dsDNA抗体、AnuA、抗DNP抗体和抗cmDNA抗体）水平的相关系数分别为（r=0.542,0.613,0.489和0.367）。具有高水平可溶性CD83的系统性红斑狼疮患者（≥2.68 ng/ml）,与各种自身抗体（抗dsDNA抗体,AnuA,抗DNP抗体和抗cmDNA抗体）水平的相关系数分别为（r=0.711,P〈0.05）、（r=0.845,P〈0.01）、（r=0.862,P〈0.01）和（r=0.724,P〈0.051）。结论：可溶性CD83通过活化DC细胞并激活补体系统,参与系统性红斑狼疮的发生发展,联合可溶性CD83和多种自身抗体的检测,能更明确系统性红斑狼疮患者病情的严重程度,有利于SLE的诊断和治疗。     

Diagnostic utility of APOE, soluble CD40, CD40L, and Abeta1-40 levels in plasma in Alzheimer's disease

A continuous inflammatory state is associated with Alzheimer's disease (AD) evidenced by an increase in proinflammatory cytokines around beta-amyloid (Abeta) deposits. In addition, functional loss of CD40L is shown to result in diminished Amyloid precursor proton (APP) processing and microglial activation, supporting a prominent role of CD40-CD40L in AD etiology. We therefore hypothesize that a peripheral increase in Abeta may result in corresponding increase of sCD40 and sCD40L further contributing to AD pathogenesis. We measured plasma Abeta, sCD40 and sCD40L levels in 73 AD patients and compared to 102 controls matched on general demographics. We demonstrated that Abeta(1-40), levels of sCD40 and sCD40L are increased in AD and declining MMSE scores correlated with increasing sCD40L, which in turn, correlated positively with Abeta(1-42). We then combined sCD40, sCD40L, Abeta and APOE and found that this biomarker panel has high sensitivity and specificity (>90%) as a predictor of clinical AD diagnosis. Given the imminent availability of potentially disease modifying therapies for AD, a great need exists for peripheral diagnostic markers of AD. Thus, we present preliminary evidence for potential usefulness for combination of plasma sCD40, sCD40L along with Abeta(1-40) and APOE epsilon4 in improving the clinical diagnosis of AD.     

Serum levels of total IgE and soluble CD23 in bronchial asthma

The aim of the present study was to compare, during the pollen season, serum levels of total IgE and soluble CD23 (sCD23) from patients with allergic bronchial asthma, with those from healthy subjects. Significantly higher levels of total IgE and sCD23 were found in patients with asthma compared to the control group. Both in normal controls and in asthmatic patients, a significant correlation was shown between the levels of these two molecules. In asthmatic patients, significant correlations were found for both total IgE and sCD23, with lung function measured as bronchial responsiveness to inhaled methacholine. These results suggest that in asthmatic patients, in addition to the study of total serum IgE levels, the assessment of sCD23 serum levels may be helpful in the evaluation of disease activity.     

A monoclonal antibody to CD4 domain 2 blocks soluble CD4-induced conformational changes in the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and HIV-1 infection of CD4+ cells.

The murine monoclonal antibody (MAb) 5A8, which is reactive with domain 2 of CD4, blocks human immunodeficiency virus type 1 (HIV-1) infection and syncytium formation of CD4+ cells (L. C. Burkly, D. Olson, R. Shapiro, G. Winkler, J. J. Rosa, D. W. Thomas, C. Williams, and P. Chisholm, J. Immunol., in press). Here we show that, in contrast to the CD4 domain 1 MAb 6H10, 5A8 and its Fab fragment do not block soluble CD4 (sCD4) binding to virions, whereas they do inhibit sCD4-induced exposure of cryptic epitopes on gp41 and dissociation of gp120 from virions. Two other MAbs, OKT4 and L120, which are reactive with domains 3 and 4 of CD4, have little or no effect on HIV-1 infection, syncytium formation, or sCD4-induced conformational changes in the envelope glycoproteins. The mechanisms of action of 5A8 and 6H10 can be further distinguished in syncytium inhibition assays: 6H10 blocks competitively, while 5A8 does not. We opine that 5A8 blocks HIV-1 infection and fusion by interfering with conformational changes in gp120/gp41 and/or CD4 that are necessary for virus-cell fusion.