Serum soluble CD40 ligand expression in children with Kawasaki disease in acute phase and its clinical significance / 中国综合临床

Objective:To investigate the expression of soluble CD40 ligand (sCD40L) in serum of children with Kawasaki disease at acute stage and its diagnostic value in coronary artery disease (CAL).Methods:This study adopts case-control study method. Select 127 children with Kawasaki disease admitted to Xuzhou Children's Hospital affiliated to Xuzhou Medical University from August 2021 to August 2022. They are divided into CAL group and non-CAL group according to the degree of coronary artery involvement. Select 30 healthy children who have physical examination in this hospital at the same time as the healthy control group, and select another 30 children with acute upper respiratory tract infection and fever admitted to this hospital at the same time as the fever control group.Compare the sex, age and laboratory indicators of children with Kawasaki disease with or without CAL, and compare the difference between the serum sCD40L level of children with Kawasaki disease with or without CAL and the fever control group and the healthy control group, the serum sCD40L level of children with different degrees of coronary artery dilation, and analyze the correlation between the serum sCD40L and various laboratory indicators of children with Kawasaki disease and the influencing factors of children with Kawasaki disease complicated with CAL, To evaluate the screening effect of serum sCD40L for Kawasaki disease complicated with CAL. The measurement data with normal distribution is expressed by xˉ± s, the comparison between the two groups adopts independent sample t-test, the comparison between multiple groups adopts one-way ANOVA, and the comparison between two groups adopts LSD method and Bonferroni correction; The measurement data of non-normal distribution is expressed by M( Q1, Q3), and the comparison between the two groups is conducted by Mann-Whitney U test. Pearson method and Spearman mothod were used for correlation analysis. Logistic regression model was used to analyze the influencing factors of children with Kawasaki disease complicated with CAL. The diagnostic value of serum sCD40L level in Kawasaki disease complicated with CAL was analyzed by drawing the ROC curve. Results:All 127 children with Kawasaki disease were divided into CAL group (45 cases) and non-CAL group (82 cases) according to the presence or absence of CAL. The serum level of sCD40L in CAL group was higher than that in non-CAL group, healthy control group and fever control group ((7.03±0.91) μg/L vs (4.66±1.23), (1.73±0.96), (2.21±1.08) μg/L), the difference was statistically significant (all P<0.001). The serum level of sCD40L in children with coronary artery dilation in CAL group was lower than that in children with small CAA, medium CAA and large CAA ((6.04±0.22) μg/L vs (6.95±0.69), (8.02±0.57), (8.23±0.26) μg/L), the difference was statistically significant (all P<0.001). Serum sCD40L level and platelet count (PLT), C-reactive protein (CRP), N-terminal pro brain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), IL-8 and tumor necrosis factor (TNF-α) in children with Kawasaki disease All were positively correlated ( r=0.31, P<0.001, r=0.32, P<0.001, r=0.26, P=0.003, r=0.58, P<0.001, r=0.27, P=0.002, r=0.39, P<0.001). Serum sCD40L, IL-6 and NT-proBNP were the risk factors of complicated CAL in children with Kawasaki disease (odds ratio 1.21, 1.06 and 1.01, 95% confidence interval 1.03-1.43, 1.01-1.12, 1.00-1.01, P values were 0.022, 0.011 and 0.039, respectively). The area under the curve of serum sCD40L in diagnosing Kawasaki disease complicated with CAL was 0.928 (95% confidence interval: 0.885-0.971), and the optimal critical value was 5.60 μg/L, the sensitivity was 97.8% and the specificity was 79.3%. Conclusions:The level of serum sCD40L increased in children with Kawasaki disease in acute phase, especially in children with CAL. The level of serum sCD40L increased with the severity of CAL, which is a risk factor for Kawasaki disease complicated with CAL, and has certain diagnostic value for Kawasaki disease complicated with CAL.

Influence of nicorandil on levels of hsCRP ,sCD40L and therapeutic effect of nicorandil in patients with microvascular angina pectoris / 心血管康复医学杂志

Objective :To explore influence of nicorandil on plasma levels of high sensitive C reactive protein (hsCRP) and soluble T cell CD40 ligand (sCD40L) and therapeutic effect of nicorandil in patients with microvascular angina pectoris .Methods :A total of 102 patients with microvascular angina pectoris were enrolled ,randomly and equally divided into routine treatment group (received routine comprehensive treatment ) and nicorandil group (received nic-orandil based on routine comprehensive treatment ,5mg ,3 times/d) ,both groups were treated for eight weeks . Plasma levels of hsCRP and sCD40L were measured and compared between two groups before and eight weeks after treatment ,and therapeutic effect was compared between two groups .Results : Compared with before treatment there were significant reductions in plasma levels of hsCRP and sCD 40L in both groups after eight weeks ;compared with routine treatment group after treatment ,there were significant reductions in plasma levels of hsCRP [ (2.63 ± 0.25) mg/L vs.(1.80 ± 0.28) mg/L] and sCD40L [ (71.88 ± 3.71) pg/ml vs .(55.25 ± 2.47) pg/ml] in nicorandil group , P＝0. 001 all.Total effective rate of nicorandil group was significantly higher than that of routine treatment group (78.43% vs.56.86%,P＝0.02).Conclusion :Nicorandil can significantly rise clinical effect ,reduce plasma levels of hsCRP and sCD40L in patients with microvascular angina pectoris .

Follicular helper T (Tfh) cells involves in the pathogenesis of Henoch-Sch?nlein purpura through affecting CD40/CD40L axis / 中华微生物学和免疫学杂志

Objective To investigate whether follicular helper T(Tfh) cells were involved in the development of Henoch-Sch?nlein purpura(HSP) and Henoch-Sch?nlein purpura nephritis(HSPN) in chil-dren through affecting CD40/CD40L axis. Methods Fifty-five subjects were enrolled in this study and di-vided into four groups as follows:22 children with HSP but without renal involvement(Group A),11 chil-dren with HSPN presenting with microhematuria(Group B),11 children with HSPN presenting with micro-hematuria and proteinuria (Group C) and 11 healthy children (control group). Flow cytometry was per-formed to detect the percentages of CD19+B cells and their subsets,CD19+B cells and CD19+CD38+B cells secreting different Ig classes,CD19+CD40+B cells and their subsets and Tfh cells expressing CD40 ligand (CD40L). Results Compared with the control group,the percentages of CD19+CD86+B,CD19+CD138+B and CD40L+Tfh cells significantly increased in Group C(P<0.05) and slightly increased in Groups A and B (P>0.05). No significant difference in the percentages of CD19+B cells, CD19+CD27+B cells, CD19+B cells or CD19+CD38+B cells expressing IgG, IgM, IgD, CD19+B cells or CD19+B cell subsets secreting CD40 was found between the control group and Groups A,B and C(P>0.05). Moreover,the percentages of CD19+B and CD19+CD38+B cells secreting IgA and IgE in Groups A,B and C were higher than those in the control group(P<0.05). Secretion of IgA by CD19+B and CD19+CD38+B cells were positively correla-ted with the expression of CD40L by Tfh cells(P<0.05). Conclusion Tfh cell-mediated abnormal expres-sion of CD40/CD40L might play an important role in the development of HSP and be related to the clinical severity of renal involvement in HSPN.

Influence of urokinase on expression of soluble CD40 ligand in patients with acute coronary syndrome / 心血管康复医学杂志

Objective: To explore influence of urokinase on expression of soluble CD40 ligand (sCD40L) in patients with acute coronary syndrome (ACS).Methods: A total of 94 ACS patients diagnosed and treated in our hospital from Aug 2013 to Aug 2015 were selected.According to random number table, they were randomly and equally divided into routine treatment group and urokinase group (received small dose urokinase intravenous drip based on routine treatment group).Levels of sCD40L and cardiac troponin T (cTnT) before and after treatment, therapeutic effect and incidence rate of major adverse cardiovascular events (MACE) were measured and compared between two groups.Results: Compared with before treatment, there were significant reductions in levels of sCD40L and cTnT in both groups after treatment, P<0.01 all;compared with routine treatment group after treatment, there were significant reductions in levels of sCD40L [(2.92±0.36) ng/ml vs.(2.58±0.18) ng/ml] and cTnT [(0.10±0.02) μg/L vs.(0.04±0.01) μg/L] in urokinase group, P=0.013, 0.001 successively.Compared with routine treatment group, there was significant rise in total effective rate (76.6% vs.95.7%),and significant reduction in incidence rate of MACE (34.0% vs.4.3%) within six months in urokinase group (P<0.01 both).Conclusion: Urokinase can significantly inhibit expression of sCD40L and reduce release of cTnT, and improve therapeutic effect, and prevent major adverse cardiovascular events in patients with acute coronary syndrome.

Associations of serum soluble CD40 ligand levels with stroke risk, severity, and infarct volume / 国际脑血管病杂志

Objective To investigate the associations of serum soluble CD40 ligand (sCD40L) levels with stroke risk,severity,and infarct volume.Methods Consecutive inpatients with acute ischemic stroke were recruited as a patient group.Healthy subjects were used as a control group.The demographics,vascular risk factors,and clinical data were collected from the patient group and control group.The serum sCD40L levels were measured by enzyme linked immunosorbent assay.According to the baseline National Institutes of Health Stroke Scale (NIHSS) scores,they were divided into a mild stroke group (＜ 8) and a moderate to severe stroke group (≥ 8).According to the median of infarct volume,the patients with ischemic stroke were divided into either a large infarction group or a small infarction group.Results A total 106 patients with acute ischemic stroke were recruited,including 47 females (44.3％) and 59 males (55.7％),and the mean age was 71.31 ± 11.27 years.There were 86 healthy subjects in the control group,including 41 females (47.7％) and 45 males (52.3％),the mean age was 73.56±9.32 years;there were.41 patients (38.7％) in large infarction group (≥1.8 cm3) and 65 (61.3％) in the small infarction group (＜1.8 cm3);there were 69 patients (65.1％) with mild stroke and 37 (34.9％) with moderate to severe stroke.The baseline serum sCD40L level in the patient group was significantly higher than that in the control group (5.61 ± 1.68 mg/L vs.3.56 ± 1.32 mg/L;t =9.236,P ＜0.01),the serum sCD40L level at day 14 after admission (4.19 ± 1.45 mg/L) in the patient group was significantly lower than the baseline level (P ＜0.01),but it was still higher than the control group (P ＜ 0.01).Multivariate logistic regression analysis showed that the higher low-density lipoprotein cholesterol (odds ratio [OR] 3.358,95％ confidence interval [CI] 2.681-4.056;P＜0.001) and serum sCD40L (OR 5.103,95％ CI 2.317-8.903;P＜0.001) levels were the independent risk factors for ischemic stroke;the higher serum sCD40L level (fourth vs.first quartile,OR 4.017,95％ CI 1.608-10.037;P =0.003),large atherosclerotic stroke (OR 2.321,95％ CI 1.014-5.314;P =0.046),cortical-subcortical infarcts (OR 2.679,95％ CI 1.111-6.460;P =0.028),and larger infarct volume (OR 3.216,95％ CI 1.398-7.395;P=0.006) were the independent risk factors for moderate to severe stroke;the higher serum sCD40L level (fourth vs.first quartile,OR 3.142,95％ CI 1.274-7.745;P =0.013),large atherosclerotic stroke (OR 2.956,95％ CI 1.299-6.767;P =0.010),cortical-subcortieal infarcts (OR 4.750,95％ CI 1.909-11.818;P ＜0.001),and baseline NIHSS score ≥8 (OR 8.509,95％ CI 3.432-21.094;P ＜ 0.001) were the independent risk factors for large infarction.Conclusion The serum sCD40L levels are closely associated with the risk,severity and infarct volume of ischemic stroke.

Effect ofXuebijinginjection on the serum soluble CD40 ligand and lipoprotein associated phospholipase A2 of patients with acute coronary syndrome / 国际中医中药杂志

Objective To detect the effect ofXuebijing injection on the serum soluble CD40 ligand (soluble CD40 ligand, sCD40L), lipoprotein associated phospholipase A2 (lipoprotein-phospholipase A2, Lp-PLA2) of patients with acute coronary syndrome (ACS).Methods A total of 120 patients with ACS were randomized divided into the control group and treatment group, 60 in each group.The control group received the routine treatment of Western medicine, and the treatment group receivedXuebijing injectionbased on the intervention of control group. Both groups were treated for 2 weeks. ELISA method was used to detect serum sCD40L, Lp-PLA and IL-6, TNF-α and CRP.Results After treatment, the serum sCD40L(320.62 ± 35.81 pg/Lvs. 401.70 ± 4.84 pg/L, t=10.435), Lp-PLA2 (203.62 ± 33.13μg/L vs. 296.45 ± 4.422μg/L,t=12.831) level was significantly lower than those in the control group (P<0.01); The serum CRP (3.10 ± 2.00 mg/Lvs.4.74 ± 2.04 mg/L,t=4.006), IL-6 (2.10 ± 1.20 pg/Lvs.3.14 ± 1.40 pg/L,t=3.781), TNF (2.81 ± 1.50 pg/Lvs. 3.70 ± 1.70 pg/L,t=3.075) level was significantly lower than thosein the control group (P<0.01 orP<0.05). Compared with the control group, the effect rate (68.3%vs. 50.0%,χ2=4.174) of the treatment group was significantly higher (P=0.041).ConclusionXuebijing injection can improve the therapeutic effectof ACS patients, and reduce CD40L, Lp-PLA2 levels.

Role of cardiovascular disease markers in periodontal infection: Understanding the risk.

Context: Both periodontitis and cardiovascular diseases (CVD) represent chronic inflammatory conditions, and periodontal infections have been postulated to perpetuate the progression of CVD’s. However, limited evidence is available to prove the causal relationship. Aim: An effort in exploring this interrelation has been made in this study. The role of two inflammatory mediators, soluble CD40 ligand (sCD40 L) and monocyte chemoattractant protein‑1 (MCP‑1) has been established in progression and acute precipitation of CVD’s. Due to a close link between these two mediators, the present study was designed to correlate the levels of sCD40 L and MCP‑1 in serum and gingival crevicular fluid (GCF) of patients with chronic periodontitis. Methods: Fifteen healthy and 30 patients of severe chronic periodontitis (diseased) participated in the study. Patients of the diseased group underwent scaling/root planning. The evaluation of plaque index, gingival index, probing depth, clinical attachment level, and a collection of serum and GCF samples was done at baseline and 6 weeks following periodontal therapy. The sCD40 L and MCP‑1 levels were quantified using ELISA. Results: The sCD40 L levels correlated strongly with MCP‑1 levels in both GCF (r = 0.888) and serum (r = 0.861) in patients of chronic periodontitis. The relationship between the levels of the two markers was maintained in GCF (r = 0.868) and serum (r = 0.750) after Phase I periodontal therapy. Conclusions: The positive correlation observed suggests this pathway as one of the mechanisms that may lead to increasing severity of periodontal disease and its systemic effects. Further research efforts should be made in designing appropriate clinical trials, starting at an early stage and monitoring the potential benefits of maintenance of oral hygiene on cardiovascular health.

Dynamic alteration of CD154/CD40 and its effects on Th1/Th2 polarization in indu-cible co-stimulator ligand knockout mice infected with Schistosoma japonicum / 北京大学学报(医学版)

Objective:To analyze effect on the CD154-CD40 signaling pathway and Th1/Th2 polariza-tion by deficient inducible co-stimulator ( ICOS)-ICOS ligand ( ICOSL) signaling in mice infected with Schistosoma japonicum. Methods:ICOSL knockout ( ICOSL-KO) mice and wild-type C57BL/6J mice were used as experimental Schistosomiasis model infected with Schistosoma japonicum. The expressions of CD154 and CD40 on splenocytes and on inflammatory cells around granulomatous infiltration of liver in mice infected with Schistosoma japonicum were analyzed by flow cytometry,immunohistochemical staining, respectively, on the day before infection (0 week) and at the end of 4, 7, 12, 16 and 20 weeks post-infection. The splenocytes of the mice were stimulated with soluble egg antigen( SEA) for 72 hours, then the concentrations of interferon gamma(IFN-γ) and interleukin-4 (IL-4) in the culture supernatants were measured by sandwich enzyme-linked immunosorbent assay ( ELISA) kits. The levels of SEA-specific an-tibodies of IgG and IgG1 and IgG2a were measured in the mice sera by ELISA. The granulomatous pa-thology in the mice liver was dynamically observed by hematoxylin and eosin ( HE ) staining. Results:Compared with the wild-type C57BL/6J mice, the expressions of CD154 on CD4 + T splenocytes [(18. 62 ± 4. 76)% vs. (27. 91 ± 3. 94)%, (22. 44 ± 4. 67)% vs. (40. 86 ± 5. 21)%, (25. 50 ± 6. 81)% vs. (43. 81 ± 8. 41)%, (20. 22 ± 5. 28)% vs. (40. 95 ± 7. 34)%, (17. 87 ± 4. 59)% vs. (33. 16 ± 6. 31)%, all P <0. 01] and of CD40 on CD19 + B splenocytes [(19. 43 ± 3. 26)% vs. (24.37 ±3.59)%, (23. 00 ± 4. 47)% vs. (31. 80 ± 5. 86)%, (24. 46 ± 5. 01)% vs. (35. 85 ± 5. 32)%, (23. 42 ± 4. 69)% vs. (33. 30 ± 6. 14)%, (22. 85 ± 3. 78)% vs. (30. 88 ± 5. 94)%, all P<0 . 05 ] in the ICOSL-KO mice significantly decreased at the end of 4 , 7 , 12 , 16 and 20 weeks post-infection. Moreover, the expressions of CD154[(0. 319 ± 0. 066) vs. (0. 488 ± 0. 086), (0. 389 ± 0. 067) vs.(0.596±0.082),(0.378±0.064) vs.(0.543±0.072),(0.348±0.069) vs.(0.523±0.076), all P<0. 01] and CD40[ (0. 398 ± 0. 066) vs. (0. 546 ± 0. 079), (0. 461 ± 0. 085) vs. (0. 618 ± 0. 076), (0. 453 ± 0. 087) vs. (0. 587 ± 0. 074), (0. 449 ± 0. 065) vs. (0. 565 ± 0. 082), all P <0 . 05 ] on inflammatory cells around granulomatous infiltration in liver from the ICOSL-KO mice were sig-nificantly lower than those of the wild-type C57 BL/6 J mice at the end of 7 , 12 , 16 and 20 weeks post-in-fection. The levels of IFN-γ of the ICOSL-KO mice were significantly higher than those of the wild-type C57BL/6J mice at the end of 4, 7, 12, 16 and 20 weeks post-infection (P <0. 05). However, the levels of IL-4 of the ICOSL-KO mice were significantly lower than those of the wild-type mice ( P <0. 05). Compared with the wild-type C57BL/6J mice, the levels of SEA-specific antibodies of IgG and IgG1 and IgG2a in the sera of the ICOSL-KO mice significantly decreased (P<0. 01). Moreover, The Th2 differentiation index of the ICOSL-KO mice was significantly lower than that of the wild-type mice in post-infection (P<0. 01). Also, the ratio of IgG1/IgG2a of the ICOSL-KO mice were significantly lower than that of the wild-type mice at the end of 7 , 12 and 16 weeks post-infection ( P<0 . 05 ) . And the vo-lume of liver egg granulomas of the ICOSL-KO mice was significantly smaller than that of the wild-type mice ( P <0 . 01 ) . Conclusion: These findings suggest that there is obvious down-regulation in the expressions of CD154 and CD40 and impairment of Th2 immune response in the ICOSL-KO mice infected with Schistosoma japonicum, accompanying with notedly reduced hepatic granulomatous pathology. The ICOS-ICOSL signaling has a regulatory effect on CD154-CD40 signaling pathway, and may play an impor-tant role in the hepatic egg granuloma formation of Schistosomiasis.

Soluble CD40L promotes proliferation of orbital fibroblasts and expression of hyaluronan synthase in patients with thyroid associated ophthalmopathy / 第二军医大学学报

Objective To investigate the effects of soluble CD40L (sCD40L) on proliferation of orbital fibroblasts (OFs) and the expression of three types of hyaluronan synthase (HAS) in vitro, so as to explore the role of sCD40L in the pathogenesis of thyroid-associated ophthalmopathy (TAO). Methods OFs obtained from 5 patients with TAO and 3 normal controls were primarily culutred. The effect of different concentrations of sCD40L (6.25,12.5,25,50,100 and 200 ng/mL) on proliferation of OFs of different sources were examined by MTS after 48 h exposure. OFs were also cultured with different concentrations of sCD40L (12.5, 25, 50 and 100 ng/mL) for 3,6,12 and 24 h, and then the expression levels of HAS 1-3 mRNA were determined by real-time RT-PCR. Results Treatment with sCD40L at concentrations higher than 25 ng/mL for 48 h obviously promoted the proliferation of OFs in patients with TAO (P<0.05). In contrast, treatment with sCD40L only at concentrations higher than 50 ng/mL for 48 h could promote proliferation of OFs from normal control, and the effect was comparatively weak. HAS3 mRNA expression of OFs in TAO patients was increased after exposed to sCD40L (P<0.05), and the increase was in a concentration- and time-dependent manner. Conclusion sCD40L can promote the proliferation of OFs and expression of HAS3 mRNA in patients with TAO, which implies that sCD40L plays an important role in the pathogenesis of TAO.

Injury effect of recombinant soluble human CD40 ligand on human um-bilical vein endothelial cells / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the damage in human umbilical vein endothelial cells ( HUVECs) induced by recombinant soluble human CD40 ligand (rshCD40L).METHODS:The cultured HUVECs were treated with rshCD40L for 12 h.The survival activity of the HUVECs was observed by MTS assay.The expression of E-selectin, intercellular ad-hesion molecule (ICAM)-1, tissue factor (TF) and tissue factor pathway inhibitor (TFPI) was measured by ELISA.The activity of superoxide dismutase ( SOD) and the level of malondialdehyde ( MDA) were detected by the methods of thibabi-turic acid (TBA) .RESULTS:Compared with normal group, different concentrations of rshCD40L (0.5, 1, 2, 3 mg/L) had no obvious effect on the survival activity of the HUVECs (P>0.05).rshCD40L at concentration of 0.5 mg/L promo-ted the secretion of E-selectin, sICAM-1, TF and TFPI in the HUVECs (P<0.01).rshCD40L at concentration of 0.5 mg/L also increased MDA content and reduced the activity of SOD in the HUVECs (P<0.05).CONCLUSION:0.5~3mg/L rshCD40L has no obvious effect on endothelial cell survival, but already causes endothelial dysfunction by increas-ing endothelial inflammation and exogenous coagulation reaction, inducing lipid peroxides injury and reducing antioxidant capacity.

Expression of Blimp1 mRNA in the PBMCs of patients with RA and the corresponding regulation of IL-21 / 中华检验医学杂志

Objective To Investigate the expression of IL-21 and Blimp1 mRNA in Rheumatoid arthritis ( RA) patients and the influence on the expression of Blimp 1 in peripheral blood mononuclear cells (PBMCs) of RA patients after IL-21 stimulated; To further explore the mechanism of IL-21 and blimp1 in the pathogenesis of RA.Methods Case control study.The samples of peripheral venous blood from 50 RA patients of department of rheumatology of The First Affiliated Hospital of Zhengzhou University and 50 healthy people were collected respectively , then the plasma and PBMCs was separated.IL-21 in plasma was measured by ELISA; the correlation between patients clinical index DAS 28, anti-CCP antibody and IL-21 was analyzed.Blimp1 mRNA of patients′PBMCs was detected by qPCR; PMBCs were isolated from RA patient and then cultured in vitro.Blimp1 mRNA level was measured by qPCR and the ratio of CD 20 positive B cell and the ratio of CD138 positive cells in all groups were detected by flow cytometry after 72 h stimulated by IL-21 and CD40L.Results IL-21 content in RA patient blood plasma (130.51 ±11.35)ng/L was significantly higher than that in healthy control (25.46 ±6.05)ng/L, t=5.39,P<0.05.Besides, IL-21 level also had a close relativity with patients DAS28(r=0.658) and anti-CCP antibody (r=0.674, P=0.039 and 0.035).In addition, the expression level of Blimp1 mRNA in RA patient PMBCs (1.321 ± 0.11)was higher than that in healthy control group (1.000 ±0.000), Z=-2.48, P<0.05.While after IL-21 and/or CD40L stimulation, Blimp1 mRNA of IL-21 group and CD40L+IL-21 group(1.084 ±0.029, 1.157 ±0.028)were higher than those of control (1.000 ±0.000)(P=0.002,P=0.001), moreover the expressive level of Blimp1mRNA of CD40L+IL-21 group was higher than that of control group (t=4.862, P=0.02).Compared to negative control group , the ratio of CD20 positive B cells [2.42 ±0.35, 2.63 ± 0.33, 6.35(4.85,6.57),F=278.363,P<0.001] and the ratio of CD138 positive cells(0.474 ±0.110, 0.668 ±0.120, 0.955 ±0.170,F=49.01, P<0.001) in CD40L group, IL-21 group and CD40L+IL-21 group were much higher and the differences among CD 40L+IL-21 group with CD40L group and IL-21 group were statistically significant.Conclusion IL-21 could promote the level of Blimp 1 mRNA in peripheral blood mononuclear cells in RA patient; IL-21 and CD40L could co-promote B cell maturation though regulating Blimp1 mRNA expression and eventually participate in RA pathogenesis.

The influence of CsA in CD40/CD40 ligand expression of T lymphocytes in patients with coronary artery disease / 天津医药

Objective To investigate the effect of CD40/CD40 ligand on the genesis and development of coronary artery disease (CAD),and the inhibitory effect of cyclosporine A (CsA) on CD40/CD40 ligand. Methods A total of 71 patients were divided into four groups:acute myocardial infarction group (AMI, n=19), unstable angina pectoris group (UAP, n=18), stable angina pectoris group (SAP, n=17) and normal control group (N, n=17). Flow cytometry was used to detect the expres?sion of CD40 and CD40L in peripheral blood mononuclear cells (PBMCs) of four groups. The group in which CD40 and CD40L were produced at the highest level was chosen, and a series concentrations of CsA(H1:0 mg/L, H2:0.01 mg/L, H3:0.1 mg/L, H4:1 mg/L)were used to treat the cells. Then the expressions of CD40 and CD40L were measured by flow cytome?try. Results Compared with N group,the expression of CD40 was significant higher in other groups (P0.05). The expression of CD40L was elevated and fol?lowed by different severity of CAD. There was significant difference in the expression of CD40L between groups (P<0.05) . AMI group showed the highest expression of CD40 and CD40L. After being treated with CsA, the expression of CD40 was higher in H1 group than that of H3 group and H4 group (P<0.05). The expression of CD40L was significantly higher in H1 group than that of other three groups (P < 0.05). Conclusion CD40 and CD40L may be involved in the development of CAD. Moreover, it might be restrained by CsA via regulation of CD40/CD40L.

The expression and clinical value of CD40 ligand(CD154) and CD4+CD25+FoxP3+ regulatory T cells in patients with ankylosing spondylitis / 中国基层医药

Objective To investigate the levels and clinical value of the peripheral blood CD154 and CD4+CD25+FoxP3+ regulatory T cells in patients with ankylosing spondylitis (AS).Methods 20 patients with AS and 20 healthy donors were studied.Flow cytometry was used to analyze the levels of the peripheral blood CD154,CD4+CD25+FoxP3+ regulatory T cells and HLA-B27.And T-test,Spearman correlation analysis were used in statistical analysis.Results The level of the peripheral blood CD154 was significantly higher in AS patients than that in normal controls [(4.38 ± 1.64) ％ vs.(1.92 ± 1.13) ％ (t =5.836,P ＜ 0.05)],and the level of the peripheral blood CD4+CD25+FoxP3+ regulatory T cells was lower in AS patients than that in normal controls [(3.87 ± 1.11) ％ vs.(6.30 ± 1.46) ％ (t =6.254,P ＜ 0.05)].There was negative correlation between the peripheral blood CD154 and CD4+CD25+FoxP3+ regulatory T cells in AS (r =-0.539,P ＜ 0.05).No relationship of the peripheral blood CD154,CD4+CD25+FoxP3+ regulatory T cells with laboratory parameters were found in AS.Conclusion The levels of the peripheral blood CD154 and CD4+CD225+FoxP3+ regulatory T cells in AS are abnormal,and may be involved in the immunological pathogenesis of AS.

The relationship between serum adiponectin and inflammatory cytokines in obese Korean juveniles / 소아과

PURPOSE: Obesity is related to systemic inflammatory processes causing cardiovascular complications. Intercellular adhesion molecule-1 (ICAM-1), CD40 ligand (CD40L), P-selectin are newly described mediators of inflammation and have a significant effect in atherosclerosis. Adiponectin has shown anti-inflammatory effects in adults. The aim of this study was to evaluate the relationship between adiponectin and inflammatory mediators in children and adolescents. METHODS: Fifty children or adolescents, twenty two with a body mass index (BMI) over 95th percentile, and twenty eight with a BMI below 75th percentile were included in the study. Serum soluble ICAM-1 (sICAM-1), P-selectin, CD40L, lipid profiles, aspartate aminotransferase, alanine aminotransferase, glucose and insulin were measured to evaluate associations with adiponectin. Comparison of these variables was performed between the obese and the nonobese group. RESULTS: We found a adiponectin to be significant lower and sICAM-1 significant higher in the obese group compared to the nonobese group, but there were no significant differences in P-selectin and soluble CD40L. Adiponectin was negatively associated with ICAM-1 and P-selectin in the obese group. CONCLUSION: Negative associations of adiponectin with ICAM-1 and P-selectin in obese children and adolescents suggest that serum adiponectin level may represent the inflammatory status.

The Interaction Between Allelic Variants of CD86 and CD40LG: A Common Risk Factor of Allergic Asthma and Rheumatoid Arthritis

PURPOSE: Allergic asthma (AA) and rheumatoid arthritis (RA) are immune tolerance-related diseases, and immune tolerance is known to be influenced by costimulatory molecules. In this study, we sought to identify common genetic susceptibility in AA and RA. METHODS: Two hundred cases of AA, 184 cases of RA, and 182 healthy controls were recruited at the Seoul National University Hospital, Seoul, Korea. Eight single nucleotide polymorphisms (SNPs) in five genes coding costimulatory molecules, namely, -318C>T, +49A>G, and 6230G>A in CTLA4, IVS3+17T>C in CD28, -3479T>G and I179V in CD86, -1C>T in CD40, and -3458A>G in CD40LG were scored, and genetic interactions were evaluated by multifactor dimensionality reduction (MDR) analysis. RESULTS: MDR analysis revealed a significant gene-gene interaction between -3479T>G CD86 and -3458A>G CD40LG for AA. Subjects with the T/T genotype of -3479T>G CD86 and the A/A genotype of -3458A>G CD40LG were found to be significantly more likely to develop AA than those with the T/T genotype of -3479T>G CD86 and A/- genotype of -3458A>G CD40LG (adjusted OR, 6.09; 95% CI, 2.89-12.98; logistic regression analysis controlled by age). Similarly those subjects showed a significant risk of developing RA (adjusted OR, 39.35; 95% CI, 15.01-107.00, logistic regression analysis controlled by age). CONCLUSIONS: Our findings suggest that a genetic interaction between CD86 and CD40LG favors the development of both AA and RA.

Correlation between CD40-1C/T gene polymorphism and serum sCD40L / 中国医师杂志

Objective To investigate the correlation between CD40-1C/T gene polymorphism and serum soluble CD40L (sCD40L) expression in cerebral infarction.Methods According to the inclusion and exclusion criteria,select the acute large artery atherosclerosis in patients with cerebral infarction as the case group,select the same period without a history of stroke examination subjects as the control group.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology was used to detect CD40 gene polymorphism and sequencing,double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of serum sCD40L.Results A total of 209 patients with large artery atherosclerotic cerebral infarction (case group) and 87 subjects without history of stroke (control group) were included.The CC genotype (31.6％) and C allele frequency (53.8％) of the case group were significantly higher than that of the control group (17.2％,39.1％) (x2 =6.94,10.69,P ＜0.01).Case group serum sCD40L expression level was significantly higher than those in the control group [(3.97 ± 1.20) vs (2.69 ±0.88)] (t =10.19,P ＜0.001).Case group serum sCD40L expression level was different among CC,CT,and TT genotypes (F =19.22,P ＜0.001),serum sCD40L level (4.55± 1.16) of CC genotype in patients was significantly higher than that of CT (3.93 ± 1.17) and TT genotypes (3.27 ± 0.90),serum sCD40L level (3.93 ± 1.17) of CT genotype in patients was significantly higher than the TT genotype (3.27 ±0.90).The serum sCD40L expression level of the control group in the CC,CT,TT has no statistically significant differences among various genotypes [(2.91 ±0.79),(2.67 ±0.89),(2.61 ±0.91),F =0.619,P =0.541).Conclusions CD40-1C/T gene polymorphism is associated with serum sCD40L expression level in cerebral infarction,serum sCD40L level of the CC genotype was significantly higher.

Advances of CD40 ligand-CD40 and kidney diseases / 国际儿科学杂志

It has been well established that interactions between CD40 and CD40L,expressed in a variety of cell types including platelets,vascular endothelial cells,and immune cells,are actively involved in the development of glomerulonephritis,lupus nephritis,and the other kidney disease caused by immunological and unimmunological factors,and that tubular cells expression of CD40 was correlated well with the degree of tubulointerstitial inflammation and injury.The development of therapeutic strategies specifically accommodating CD40/CD40L seem promising against renal glomerular disease.The paper reviews the new advances in this

CD40-CD40 ligand in pediatric disease / 国际儿科学杂志

CD40-CD40 ligand (CD40-CD40L) cross-linking,an important cell signaling transduction pathway in immune response,is involved in the regulation of cellular and humoral immune.CD40-CD40L signaling pathway abnormalities can lead to immune system disorders and incur immune pathological reaction.A variety of common pediatric diseases,such as immunodeficiency diseases,inflammatory diseases and autoimmune diseases,are associated with CD40-CD40L signaling transduction pathway abnormalities.The relationship between CD40-CD40L and the above-mentioned diseases is of clinical significance.

CD40/CD40L system and atherosclerosis / 国际脑血管病杂志

Atherosclerosis is a chronic inflammatory disease.Atherosclerotic plaque rupture and thrombosis may result in cardio-cerebrovascular events.Inflammatory mediator CD40L widely exists in cells associated with atherosclerosis.They participate in plaque inflammatory response,release proinflammatory cytokines,degrade extracellular matrix,improve procoagulant activity,and promote the progression of atherosclerosis and plaque vulnerability.Intervening CD40/CD40L signaling system may become an effective treatment strategy to slow the progress of atherosclerosis and stabilize atherosclerotic plaques.

Relationships between plasma soluble CD40 ligand, fetuin-A and pregnancy-associated plasma protein A and carotid artery plaque in patients with ischemic stroke / 国际脑血管病杂志

Objective To investigate the relationships between the levels of plasma soluble CD40 ligand (sCD40L),fetuin-A and pregnancy-associated plasma protein A (PAPP-A) and carotid plaque in patients with acute ischemic stroke.Methods The patients with acute ischemic stroke were enrolled in the study.Carotid arteries were assessed by using carotid artery ultrasound.The patients were divided into either a carotid artery plaque group or a non-carotid artery plaque group according to the assessment results.The former were further divided into a stable plaque sub-group and an unstable plaque sub-group according the nature of plaque.Enzyme-linked immunosorbent assay was used to detect the levels of plasma sCD40L,fetuin-A and PAPP-A.The demography,previous history,complications,laboratory tests and plasma inflammatory biomarkers between the carotid artery plaque group and the non-carotid artery plaque group and between the stable plaque subgroup and the unstable plaque subgroup were compared.Multivariate logistic regression analysis was used to investigate the relationship between plasma inflammatory biomarkers and carotid plaques.Results A total of 200 patients with acute ischemic stroke were included.Among them,78 were females and 122 were males (aged 33 to 87 years,mean 60.1 ± 10.3 years); 139 patients were in the carotid artery plaque group and 61 were in the non-plaque group; 43 were in the stable plaque subgroup and 96 were in the unstable plaque subgoup.The mean age of the carotid artery plaque subgroup was significantly greater than that in the non-plaque subgroup (63.2 ± 8.7 years vs.50.3 ± 9.5 years; t ＝ 10.179,P =0.000),the constituent ratios of men (68.3％ vs.44.3％;x2＝ 10.336,P＝ 0.001),hypertension (71.2 vs.54.1％;x2=5.540,P=0.019),diabetes (46.8％ vs.29.5％ ;x2 =5.199,P =0.023),and hyperlipidemia (78.4％ vs.37.7％ ;x2 =31.31,P =0.000)in patients of carotid plaque group were significantly higher than those of the non-carotid plaque group.The levels of total cholesterol (5.7 ± 1.1 mmol/L vs.5.3 ± 1.0 mmol/L; t =2.433,P =0.016),low-density lipoprotein cholesterol (4.5 ± 1.0 mmol/L vs.4.1 ±0.9 mmol/L; t =2.683,P =0.008),fasting glucose (7.5 ±2.5 mmol/Lvs.6.4±2.1 mmol/L; t=3.002,P＝0.003),sCD40L (151.4 ± 55.8 pg/mlvs.102.8 ±65.9 pg/ml; t =5.360,P=0.000),fctuin-A (390.1 ± 80.6 μg/ml v.s.352.9 ± 98.6 μg/ml; t =2.591,P =0.011),and PAPP-A (11.49 ±4.67 mIU/L vs.8.46 ± 3.99 mIU/L; t =4.409,P =0.000) were significantly higher than those of the non-carotid plaque group.Multivariate logistic regression analysis showed that hyperlipidemia (odds ratio [OR] 6.582,95％ confidence interval [CI] 2.321-18.662; P =0.000),sCD40L (OR6.372,95％ CI 2.174-18.670;P=0.010),and fetuin-A (OR 4.101,95％ CI 1.012-16.619; P=0.048) were the independent predictors for carotid artery plaques in patients with acute ischemic stroke.The mean age of the stable plaque subgroup was significantly lower than that of the unstable plaque subgroup (59.6 ± 9.3 years vs.64.1 ± 7.2 years; t =3.231,P =0.002).The constituent ratio in patients with hypertension was significantly lower than that of the unstable plaque subgroup (55.8％ vs.78.1％ ; x2 =7.213,P =0.007).The levels of total cholesterol (5.4 ±0.9 mmol/L vs.6.0 ± 1.1 mmol/L; t =3.136,P =0.002),low-density lipoprotein cholesterol (4.0 ± 1.2 mmol/L vs.5.7 ± 1.0 mmol/L; t =8.696,P =0.000),fasting glucose (7.1 ± 2.3 mmol/L vs,7.9 ± 1.9 mmol/L; t =2.147,P =0.034),sCD40L (135.3 ±74.3 pg/ml vs.176.5 ±64.5 pg/ml; t =3.319,P ＝0.001),and PAPP-A (10.96 ± 5.02 mIU/L vs.13.98 ±4.63 mIU/L; t =3.463,P =0.001) were significantly lower than those of the unstable plaque subgroup,while the level of high-density lipoprotein cholesterol was significantly higher than that of the unstable plaque subgroup (1.2 ± 0.2 mmol/L vs.1.1 ± 0.3 mmol/L; t =2.314,P=0.022).Multivariate logistic regression analysis showed that HDL-C (OR 0.234,95％ CI0.060-0.906; P =0.022) was an independent protective factor for unstable plaques,while sCD40L (OR 5.290,95％ CI 1.613-17.351; P =0.029) and PAPP-A (OR4.125,95％ CI 1.281-13.283; P =0.021) were the independent predictors for unstable plaques.Conclusions The levels of sCD40L,PAPP-A,and fetuin-A were associated with the existence and stability of carotid artery plaque.The increased plasma sCD40L and fetuin-A were the independent predictors for carotid artery plaques in patients with acute ischemic stroke,and the increased levels of plasma sCD40L and PAPP-A were the independent predictors for carotid artery plaque instability in patients with acute ischemic stroke.