scholarly journals Cytomegalovirus may influence vascular endothelial health in Indonesian HIV-infected patients after 5 years on ART

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Ika Prasetya Wijaya ◽  
Birry Karim ◽  
Mohamad Syahrir Azizi ◽  
Ibnu Ariyanto ◽  
Arif Mansjoer ◽  
...  
Keyword(s):  
Immune Activation ◽  
Chondroitin Sulphate ◽  
Endothelial Activation ◽  
Vascular Endothelial ◽  
Healthy Controls ◽  
Vascular Health ◽  
Transplant Recipients ◽  
Hiv Patients ◽  
Flow Mediated Dilatation ◽  
Multivariable Analyses

Abstract Objectives Accelerated atherosclerosis in older HIV-infected patients has been attributed to persistent immune activation and high burden cytomegalovirus (CMV), as demonstrated in transplant recipients and the general population. Here we assess CMV and inflammatory markers linked with vascular health in young adult patients treated in Indonesia. Study design HIV-infected adults (n = 32) were examined when they began antiretroviral therapy (ART) with < 200 CD4 T-cells/µl (V0) and after 60 months (V60). Age-matched healthy controls (HC, n = 32) were assessed once. Methods Flow Mediated Dilatation (FMD) was assessed by ultrasound on brachial arteries at V60 and in HC. Plasma markers of immune activation and endothelial activation, and CMV antibodies (lysate, gB, IE-1) were assessed in all samples. Results were assessed using bivariate (non-parametric) and multivariable analyses. Results Levels of inflammatory biomarkers and CMV antibodies declined on ART, but the antibodies remained higher than in HC. FMD values were similar in patients and HC at V60. In HIV patients, levels of CMV lysate antibody correlated inversely (r = − 0.37) with FMD. The optimal model predicting lower FMD values (adjusted R2 = 0.214, p = 0.012) included CMV lysate antibodies and chondroitin sulphate. In HC, levels of sTNFR correlated inversely with FMD (r = − 0.41) and remained as a risk factor in the optimal multivariable model, with CMV glycoprotein-B (gB) antibody predicting a healthier FMD (adjusted R2 = 0.248, p = 0.013). Conclusions Higher levels CMV antibodies optimally predict vascular health measured by FMD in HIV patients. However in healthy controls, sTNFR marks risk and CMV gB antibody may be protective.

P6244Cytomegalovirus (CMV) burden may be used to enhance algorithms to predict future cardiovascular health in renal transplant recipients and healthy controls

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Affandi ◽  
S Lee ◽  
H Chih ◽  
E Brook ◽  
S Waters ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Adhesion Molecule ◽  
Pulse Wave ◽  
Healthy Adults ◽  
Intercellular Adhesion Molecule ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Vascular Health ◽  
Transplant Recipients ◽  
High Burden

Abstract Background Cytomegalovirus (CMV) has been implicated in accelerated cardiovascular changes and may warrant inclusion in predictive algorithms. This is addressed here in healthy older adults and in renal transplant recipients (RTR) stable on therapy as they retain a high burden of CMV. Methods RTR (n=45) stable >2 years after transplantation and 58 age-matched healthy adults were recruited in 2014 and returned in 2017. Venous blood samples and saliva were collected, frozen and stored. Plasma proteins linked with inflammation [soluble interferon a receptor 2 (sIFNaR2), sTNFR1, sCD14, C-reactive protein (CRP)], vasculopathy [p-selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1)], and metrics of CMV burden [antibodies reactive with CMV lysate, gB or IE-1 (by ELISA), CMV DNA in saliva (by PCR) and T-cell IFNg responses to CMV antigens (by ELISpot)] were assessed in 2014. In 2017, vascular endpoint measurements included brachial artery flow mediated dilatation (FMD), pulse wave analysis [augmented index corrected to heart rate of 75 beats per minute (Aix@75)] and pulse wave velocity (PWV). Results In 2017, RTR had lower FMD % (p<0.001), higher PWV (<0.001) and slightly higher Aix@75 values (p=0.14) compared with healthy adults, indicating inferior vascular health. In a multivariable regression model (adjusted R2=0.42) predicting 2017 FMD in RTR (adjusted for age, sex, BMI, eGFR, sCD14, CMV gB Ab and saliva CMV DNA), each 1AU/mL increase of CMV gB Ab (p=0.03) predicted a 5% increase in FMD – associating with better vascular outcomes, but detectable saliva CMV DNA (p=0.02) associated with a 3% increase in FMD. In healthy adults, however, while predicting 2017 FMD (adjusting for p-selectin, ICAM-1, age, sex, BMI, eGFR; adjusted R2=0.22), a 1 ng/mL increase in p-selectin (p=0.03) predicted a 0.04% increase in FMD, and 1 ng/mL increase in ICAM-1 (p=0.03) associated with 0.03% lower FMD. From the pulse wave analyses of RTR, every 1ng/mL increase of sIFNaR2 (p=0.06) marginally predicted 1.4 unit decrease in Aix@75 (adjusted for CMV IE-1 Ab, sIFNaR2, age, sex, BMI and eGFR; adjusted R2=0.37). However in healthy adults, each 1ng/mL increase of sIFNaR2 levels (p=0.04) associated with 3.5 units worsening of Aix@75 (p=0.04) (adjusted R2 = 0.40). Each 1 AU/mL increase in CMV IE-1 Ab levels associated with 0.08 units decrease in PWV (p=0.02) (adjusting for CMV IE-1 Ab, sCD14, age, sex, BMI and eGFR adjusted R2=0.55). Conclusions Overall measures of a high burden of CMV, predicted a low FMD marking poor peripheral vascular health in RTR several years after assessment, with more potency than was achieved with plasma markers of systemic and vascular inflammation, which was observed in healthy controls. CMV antibodies can predict future measures of arterial stiffness such as Aix@75 and PWV in healthy controls, but need further investigation in larger cohorts.

scholarly journals Immune activation in prolonged cART-suppressed HIV patients is comparable to that of healthy controls

Virology ◽  
2017 ◽  
Vol 509 ◽  
pp. 133-139 ◽  
Author(s):  
Lennert van den Dries ◽  
Mark A.A. Claassen ◽  
Zwier M.A. Groothuismink ◽  
Eric van Gorp ◽  
Andre Boonstra
Keyword(s):  
Immune Activation ◽  
Healthy Controls ◽  
Hiv Patients

Occurrence of Interleukin-2 (330 G/T) Promoter Polymorphism in ARV associated hepatotoxicity

2019 ◽  
Vol 19 (3) ◽  
pp. 206-215
Author(s):  
HariOm Singh ◽  
Nayana Nambiar ◽  
Dharmesh Samani ◽  
Raman R. Gangakhedkar
Keyword(s):  
Hepatic Injury ◽  
Interleukin 2 ◽  
Promoter Polymorphism ◽  
Healthy Controls ◽  
Hiv Replication ◽  
Hiv Patients ◽  
Pcr Rflp

Background: IL-2 cytokine is involved in HIV replication and is also known to cause hepatic injury. Polymorphisms in the IL-2 gene are associated with altered interleukin-2 production. Methods: Hence, we assessed the prevalence of IL-2-303G/T polymorphism in 165 HIV patients (34 with and 131without hepatotoxicity) and 155 healthy controls using the PCR-RFLP method. Results: In patients with hepatotoxicity, IL-2-303GT, -303GT+TT genotypes were less prevalent as compared to without hepatotoxicity and healthy controls (29.4% vs. 42.7%, 58.8% vs. 69.5%; 29.4% vs. 40.6%, 58.8% vs. 66.5%, respectively). In patients with hepatotoxicity using tobacco and alcohol, IL-2-303GT,-303TT genotypes were distributed higher as compared to non-users (42.9% vs. 25.9%, OR=8.52, 42.9% vs. 25.9%, OR=9.09, and 28.6% vs. 29.6%, OR=1.63, 42.9% vs. 25.9%, OR=2.93), while IL-2-303TT genotype occurred more often in HIV patients consuming alcohol (34.1% vs. 23.0%). Nevirapine users with hepatotoxicity overrepresented the IL-2-303GT,-303TT genotypes as compared to efavirenz (34.8% vs. 18.2%, OR=4.64, 34.8% vs. 18.2%, OR=3.88). Among nevirapine users, IL-2-303GT genotype was associated with susceptibility to the acquisition of hepatotoxicity with borderline significance (OR=4.24, P=0.06). HIV patients using nevirapine majorly represented the IL-2-303TT genotype (26.9% vs. 25.0%, OR=2.35) while HIV patients with nevirapine + alcohol usage presented the IL-2 -330TT genotype at a higher frequency (34.2% vs. 23.5%, OR=1.51). In patients with hepatotoxicity using nevirapine + alcohol, the genotype IL-2 - 330TT was predominant (60.0% vs. 27.8%, OR=3.16). Conclusion: Thus, IL-2-303G/T polymorphism did not confer the susceptibility to ARV associated hepatotoxicity. However, IL-2-303G/T polymorphism with nevirapine usage may facilitate the risk for acquisition of ARV associated hepatotoxicity.

Decreased Flow-Mediated Dilatation in Children With Type 1 Diabetes: A Systematic Review and Meta-Analysis

Angiology ◽  
2021 ◽  
pp. 000331972110100
Author(s):  
Lei Cao ◽  
Miao Hou ◽  
Wanping Zhou ◽  
Ling Sun ◽  
Jie Shen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Type 1 Diabetes ◽  
Endothelial Function ◽  
Meta Analysis ◽  
Quality Data ◽  
Cochrane Library ◽  
Healthy Children ◽  
Healthy Controls ◽  
Flow Mediated Dilatation

Type 1 diabetes (T1DM) is a strong risk factor for the development of cardiovascular disease. Flow-mediated dilatation (FMD) is an early noninvasive marker of endothelial function and it predicts future cardiovascular disease. However, the changes in FMD among T1DM children are still controversial. The present meta-analysis aimed to investigate whether FMD is impaired in children with T1DM. PubMed, EMBASE, Cochrane library, and Web of Science were searched for studies comparing FMD in children with T1DM and healthy controls. The Newcastle-Ottawa quality assessment scale for case–control studies was used to assess study quality. Data were pooled using a random effects models to obtain the weighted mean differences (WMD) in FMD and 95% CIs. Overall, 19 studies with 1245 patients and 872 healthy controls were included in this meta-analysis. Children with T1DM had significantly lower FMDs compared with healthy controls (WMD: −2.58; 95% CI: −3.36 to −1.81; P < .001). Meta-regression analysis revealed that low-density lipoprotein cholesterol levels impacted the observed difference in FMD between T1DM and healthy children. This meta-analysis showed that T1DM children have impaired endothelial function, which indicates they are at higher risk of developing cardiovascular disease in later life.

scholarly journals Higher CD19+CD25+ Bregs are independently associated with better graft function in renal transplant recipients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Eman H. Ibrahim ◽  
Mostafa G. Aly ◽  
Gerhard Opelz ◽  
Christian Morath ◽  
Martin Zeier ◽  
...  
Keyword(s):  
Renal Transplant ◽  
B Cell ◽  
Graft Function ◽  
Cell Subset ◽  
Immunosuppressive Drugs ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Significant Positive Association ◽  
Ifn Γ

Abstract Background The Identification of B cell subsets with regulatory functions might open the way to new therapeutic strategies in the field of transplantation, which aim to reduce the dose of immunosuppressive drugs and prolong the graft survival. CD25 was proposed as a marker of a B-cell subset with an immunosuppressive action termed Bregs. The effect of CD19 + CD25 + Bregs on graft function in renal transplant recipients has not yet been elucidated. We investigated a potential impact of CD19 + CD25 + Bregs on renal graft function as well as a possible interaction of CD19 + CD25 + Bregs with peripheral Tregs in healthy controls, end-stage kidney disease patients (ESKD), and renal transplant recipients. Moreover, we aimed to investigate the association of CD19 + CD25 + Bregs with serum IL-10, TGF-ß1, and IFN-γ in the same study groups. Method Thirty-one healthy controls, ninety renal transplant recipients, and eighteen ESKD patients were enrolled. We evaluated the CD19 + CD25 + Bregs and Treg absolute counts. Next, we investigated CD19 + CD25 + Bregs as predictors of good graft function in multiple regression and ROC analyses. Finally, we evaluated the association between CD19 + CD25+ Bregs and serum IL-10, TGF-ß, and IFN-γ. Results ESKD patients and renal transplant recipients showed lower counts of CD19 + CD25+ Bregs compared to healthy controls (p < 0.001). Higher CD19 + CD25+ Breg counts were independently associated with a better GFR in renal transplant recipients (unstandardized B coefficient = 9, p = 0.02). In these patients, higher CD19 + CD25+ Bregs were independently associated with higher Treg counts (unstandardized B = 2.8, p = 0.004). In ROC analysis, cut-offs for CD19 + CD25 + Breg counts and serum TGF-ß1 of 0.12 cell/μl and 19,635.4 pg/ml, respectively, were shown to provide a good sensitivity and specificity in identifying GFR ≥ 30 ml/min (AUC = 0.67, sensitivity 77%, specificity 43%; AUC = 0.65, sensitivity 81%, specificity 50%, respectively). Finally, a significant positive association between CD19 + CD25+ Bregs and TGF-ß1 was shown in renal transplant recipients (r = 0.255, p = 0.015). Conclusions Our findings indicate that higher counts of CD19 + CD25+ Bregs are independently associated with better renal function and higher absolute Treg counts in renal transplant recipients.

Carboxiterminal pro-endothelin-1 as an endothelial cell biomarker in thrombotic thrombocytopenic purpura

2016 ◽  
Vol 115 (05) ◽  
pp. 1034-1043 ◽  
Author(s):  
György Sinkovits ◽  
Péter Farkas ◽  
Dorottya Csuka ◽  
Katalin Rázsó ◽  
Marienn Réti ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Acute Phase ◽  
Complement Activation ◽  
Endothelial Activation ◽  
Factor H ◽  
Healthy Controls ◽  
Activation Markers ◽  
Thrombocytopenic Purpura ◽  
Endothelin 1

SummaryThrombotic thrombocytopenic purpura (TTP) is characterised by the deficiency of the von Willebrand factor (VWF) cleaving protease (ADAMTS-13). Although several observations indicate an important role of endothelial activation in the pathogenesis of TTP, no reliable endothelial activation markers are available in the clinical management of TTP. Our aim was to investigate the presence of endothelial activation in TTP and to determine its connections with disease activity, therapy and complement activation. We enrolled 54 patients (median age 40.5; 44 females) and 57 healthy controls (median age 34; 30 females),VWF antigen, carboxiterminal-pro-endothelin-1 (CT-proET-1), complement Factor H and complement activation products (C3bBbP and SC5b-9) were measured. In both the acute and remission phase of TTP we found increased CT-proET-1 and VWF levels, while Factor H levels decreased compared with healthy controls. In remission, however, the elevated CT-proET-1 levels showed 22 % decrease when compared with the acute phase in paired samples (p=0.0031), whereas no changes for VWF and Factor H levels were observed. We also found positive correlations between CT-proET-1 levels and alternative pathway activation markers (C3bBbP; p=0.0360; r=0.4299). The data we present here demonstrate a role of endothelium activation in patients with acute TTP. The finding that CT-proET-1 levels decreased in remission compared with the acute phase further supports endothelial involvement. In addition, we show that endothelial activation also correlated with the activation of the alternative complement pathway. The data suggest that complement and endothelium activation jointly contribute to the development of TTP episodes in patients with predisposition to TTP.Supplementary Material to this article is available online at www.thrombosis-online.com.

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