scholarly journals HIV infection is associated with reduced serum alpha-1-antitrypsin concentrations

2010 ◽  
Vol 33 (6) ◽  
pp. 384 ◽  
Author(s):  
Courtney L Bryan ◽  
K Scott Beard ◽  
Gregory B Pott ◽  
Jeremy Rahkola ◽  
Edward M Gardner ◽  
...  

Purpose: Several observations suggest the presence of HIV-suppressive factors in the fluid phase of blood. Alpha-1-antitrypsin (AAT), the most abundant serine protease inhibitor in the circulation, has potent anti-HIV activity in vitro, and may function as an endogenous HIV suppressor. Therefore, we assessed serum AAT concentrations for association with HIV infection. Methods: In this cross-sectional study, serum AAT concentrations were measured in 66 persons with HIV infection and in 45 healthy persons (Controls). In the HIV-infected group, antiretroviral therapy (ART) use was assessed and CD4+ T cell levels and plasma HIV RNA were quantified. Results: Median AAT concentration was significantly lower in the HIV-infected group (1.64 mg/mL) in comparison with Controls (1.94 mg/mL; p=0.001). AAT reduction was most pronounced in the HIV-infected subgroup with CD4+ T cell levels > 200 cells/µL in comparison with Controls (p < 0.01). Serum AAT concentrations < 1.0 mg/mL are clinically significant, and concentrations below this level were identified in 4.5% of the HIV-infected group and in no Control subjects. No association between AAT levels and viral load or use of ART was observed in HIV-infected subjects. Conclusion: The association between reduced serum AAT concentration and HIV infection is consistent with a role for AAT as an endogenous HIV suppressor.

PLoS ONE ◽  
2012 ◽  
Vol 7 (9) ◽  
pp. e45911 ◽  
Author(s):  
Catherine M. Card ◽  
W. John Rutherford ◽  
Suzie Ramdahin ◽  
Xiaojian Yao ◽  
Makobu Kimani ◽  
...  

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0119326 ◽  
Author(s):  
Elisabeth Kleppa ◽  
Kari F. Klinge ◽  
Hashini Nilushika Galaphaththi-Arachchige ◽  
Sigve D. Holmen ◽  
Kristine Lillebø ◽  
...  

2020 ◽  
Vol 94 (22) ◽  
Author(s):  
Sushant Khanal ◽  
Qiyuan Tang ◽  
Dechao Cao ◽  
Juan Zhao ◽  
Lam Nhat Nguyen ◽  
...  

ABSTRACT CD4 T-cell depletion is a hallmark of HIV/AIDS, but the underlying mechanism is still unclear. We have recently shown that ataxia-telangiectasia-mutated (ATM) deficiency in CD4 T cells accelerates DNA damage, telomere erosion, and cell apoptosis in HIV-infected individuals on antiretroviral therapy (ART). Whether these alterations in ART-treated HIV subjects occur in vitro in HIV-infected CD4 T cells remains unknown. In this study, we employed a cellular model of HIV infection to characterize the mechanisms underlying CD4 T-cell destruction by analyzing the telomeric DNA damage response (DDR) and cellular apoptosis in highly permissive SupT1 cells, followed by the validation of our observations in primary CD4 T cells with active or drug-suppressed HIV infection. Specifically, we established an in vitro HIV T-cell culture system with viral replication and raltegravir (RAL; an integrase inhibitor) suppression, mimicking active and ART-controlled HIV infection in vivo. We demonstrated that HIV-induced, telomeric DDR plays a pivotal role in triggering telomere erosion, premature T-cell aging, and CD4 T-cell apoptosis or depletion via dysregulation of the PI3K/ATM pathways. This in vitro model provides a new tool to investigate HIV pathogenesis, and our results shed new light on the molecular mechanisms of telomeric DDR and CD4 T-cell homeostasis during HIV infection. IMPORTANCE The hallmark of HIV infection is a gradual depletion of CD4 T cells, with a progressive decline of host immunity. How CD4 T cells are depleted in individuals with active and virus-suppressed HIV infection remains unclear. In this study, we employed a cellular model of HIV infection to characterize the mechanisms underlying CD4 T-cell destruction by analyzing the chromosome end (telomere) DNA damage response (DDR) and cellular apoptosis in a T-cell line (highly permissive SupT1 cells), as well as in primary CD4 T cells with active or drug-suppressed HIV infection. We demonstrated that HIV-induced telomeric DDR plays a critical role in inducing telomere loss, premature cell aging, and CD4 T-cell apoptosis or depletion via dysregulation of the PI3K/ATM pathways. This study sheds new light on the molecular mechanisms of telomeric DDR and its role in CD4 T-cell homeostasis during HIV infection.


2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
R. Chandran ◽  
L. Feller ◽  
J. Lemmer ◽  
R. A. G. Khammissa

Objective. The aim of the study was to determine the prevalence of HIV-associated oral mucosal melanin hyperpigmentation (HIV-OMH) in a specific population of HIV-seropositive South Africans and to analyse the associations between HIV-OMH clinical features and the demographic and immunological characteristics of the study cohort.Material and Methods. This cross-sectional study included 200 HIV-seropositive Black subjects. The collected data comprised age, gender, CD4+ T cell count, viral load, systemic disease, medications, oral site affected by HIV-OMH, extent (localized or generalized), intensity of the pigmentation (dark or light), and smoking and snuff use.Results. Overall, 18.5% of the study cohort had HIV-OMH. Twenty-two and a half percent had OMH that could not with confidence be attributed to HIV infection, and 59% did not have any OMH. There was a significant but weak association between smoking and the presence of HIV-OMH.Conclusions. The prevalence of HIV-OMH in the study population was 18.5%, the gingiva being the most commonly affected site. It appears that the CD4+ T cell count does not play any role in the biopathology of HIV-OMH.


2007 ◽  
Vol 19 (2) ◽  
Author(s):  
Irna Sufiawati ◽  
Harum Sasanti ◽  
Samsuridjal Djauzi

Background: HIV infection appears to have direct effects on oral mucosal immunity, cellular and humoral. Antibody secretion, especially salivary immunoglobulin A (IgA), is a useful indicator of mucosal immune function. This immune system component is recognized as an important first-line of defence against pathogens which colonize and invade mucosal surfaces in the oral cavity. Objectives: The purpose of this study was to investigate salivary IgA levels and to determine its correlation with CD4+ T-cell counts among HIV-infected patients in Pokdisus AIDS Cipto Mangunkusomo Hospital Jakarta. Methods: The design study was using a cross-sectional study. Whole paraffin-wax-stimulated saliva was collected from 103 HIV-infected patients and 30 healthy individuals. Saliva was collected using the spitting method. Salivary IgA levels were determined by the immunoturbidimetry method using the Behring Turbitimer Analyser. CD4+ T-cell counts were analyzed by flow cytometry. Results: Salivary IgA levels were 141.55 ± 83.23 (HIV group) and 97.24 ± 38.25 (healthy individuals). The Mann-Whitney U test showed salivary IgA levels were significantly higher in HIV/AIDS subjects compared with healthy individuals (p<0.1). Most of the subject has severe immunosuppression with CD4+ T-cell counts <200 cell/mm.3 Pearson’s correlation test between CD4+ T-cell counts and salivary IgA levels showed no significant correlation (r= 0.06, p>0.1). Conclusion: This study indicates that total salivary IgA levels were significantly higher in the HIV-infected patients compared to control, and salivary IgA level seems not to be related significantly to CD4+ T-cell counts.


Blood ◽  
1999 ◽  
Vol 94 (3) ◽  
pp. 1021-1027 ◽  
Author(s):  
Elaine M. Sloand ◽  
Princy N. Kumar ◽  
Sonnie Kim ◽  
Aniruddho Chaudhuri ◽  
Frank F. Weichold ◽  
...  

CD4+ T cells from patients with human immunodeficiency virus (HIV) infection undergo apoptosis at an increased rate, which leads to their depletion during disease progression. Both the Fas-Receptor (Fas-R) and interleukin-1β (IL-1β)–converting enzyme (ICE; caspase 1) appear to play a role in the mechanism of apoptosis of CD4+ lymphocytes. Although Fas-R is upregulated on both CD4+ and CD8+ cells in HIV-infected patients, results from our laboratory and others indicate that, in patients with advanced disease, CD4+ cells preferentially express ICE. Protease inhibitors have successfully halted the progression of HIV disease and increased CD4+ T counts. In this study, we examined the effect of protease inhibitors on Fas-R (CD95), ICE (caspase 1) expression, apoptosis, and cell death in CD4+ T cells of (1) HIV-infected patients who were receiving protease inhibitors, and (2) normal and patient CD4+ T cells cultured with a protease inhibitor in vitro. Fifteen patients with advanced HIV disease on treatment showed dramatically decreased CD4+ T-cell ICE expression, diminished apoptosis, and increased numbers of CD4+ cells within 6 weeks of institution of protease inhibitor therapy, and before down-modulation of Fas-R (CD95) expression was evident. To determine the role of HIV infection, we studied the effect of ritonavir, a protease inhibitor, on normal and patient cells in vitro. Stimulated and unstimulated normal CD4+ T cells, cultured with protease inhibitor, demonstrated markedly decreased apoptosis and ICE expression (P = .01). While Fas-R expression was not significantly altered during short-term culture by such treatment, Fas-Ligand (Fas-L) membrane expression of phytohemagglutinin (PHA)-stimulated blood lymphocytes was decreased by protease inhibitor. In the presence of ritonavir, CD4+ T cells from HIV-infected patients showed similar changes in ICE intracellular levels without alteration of Fas expression. In conclusion, protease inhibitors appear to decrease CD4+ T-cell ICE expression and apoptosis before they affect Fas-R expression in HIV-infected patients. This action was independent of HIV infection, as similar effects were seen in CD4+ T cells from normal controls. Some of the benefit of protease inhibitors may be related to modification of programmed cell death, which increases CD4+ T-cell number. Whether this is due to directly to the changes effected in the caspase system remains to be determined.


2019 ◽  
Author(s):  
David Zendle

A variety of practices have recently emerged which are related to both video games and gambling. Most prominent of these are loot boxes. However, a broad range of other activities have recently emerged which are also related to both gambling and video games: esports betting, real-money video gaming, token wagering, social casino play, and watching videos of both loot box opening and gambling on game streaming services like Twitch.Whilst a nascent body of research has established the robust existence of a relationship between loot box spending and both problem gambling and disordered gaming, little research exists which examines whether similar links may exist for the diverse practices outlined above. Furthermore, no research has thus far attempted to estimate the prevalence of these activities.A large-scale survey of a representative sample of UK adults (n=1081) was therefore conducted in order to investigate these issues. Engagement in all measured forms of gambling-like video game practices were significantly associated with both problem gambling and disordered gaming. An aggregate measure of engagement was associated with both these outcomes to a clinically significant degree (r=0.23 and r=0.43). Engagement in gambling-like video game practices appeared widespread, with a 95% confidence interval estimating that 16.3% – 20.9% of the population engaged in these activities at least once in the last year. Engagement in these practices was highly inter-correlated: Individuals who engaged in one practice were likely to engage in several more.Overall, these results suggest that the potential effects of the blurring of lines between video games and gambling should not primarily be understood to be due to the presence of loot boxes in video games. They suggest the existence of a convergent ecosystem of gambling-like video game practices, whose causal relationships with problem gambling and disordered gaming are currently unclear but must urgently be investigated.


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