Displaying publications 1 - 20 of 34 in total

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  1. Shankar EM, Velu V, Kamarulzaman A, Larsson M
    World J Virol, 2015 Feb 12;4(1):17-24.
    PMID: 25674514 DOI: 10.5501/wjv.v4.i1.17
    Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis.
  2. Shankar EM, Vignesh R, Ellegård R, Barathan M, Chong YK, Bador MK, et al.
    Pathog Dis, 2014 Mar;70(2):110-8.
    PMID: 24214523 DOI: 10.1111/2049-632X.12108
    Tuberculosis (TB) and human immunodeficiency virus (HIV) infection interfere and impact the pathogenesis phenomena of each other. Owing to atypical clinical presentations and diagnostic complications, HIV/TB co-infection continues to be a menace for healthcare providers. Although the increased access to highly active antiretroviral therapy (HAART) has led to a reduction in HIV-associated opportunistic infections and mortality, the concurrent management of HIV/TB co-infection remains a challenge owing to adverse effects, complex drug interactions, overlapping toxicities and tuberculosis -associated immune reconstitution inflammatory syndrome. Several hypotheses have been put forward for the exacerbation of tuberculosis by HIV and vice versa supported by immunological studies. Discussion on the mechanisms produced by infectious cofactors with impact on disease pathology could shed light on how to design potential interventions that could decelerate disease progression. With no vaccine for HIV and lack of an effective vaccine for tuberculosis, it is essential to design strategies against HIV-TB co-infection.
  3. Shankar EM, Che KF, Yong YK, Girija ASS, Velu V, Ansari AW, et al.
    Pathog Dis, 2021 Jan 09;79(1).
    PMID: 33289808 DOI: 10.1093/femspd/ftaa076
    A vast proportion of coronavirus disease 2019 (COVID-19) individuals remain asymptomatic and can shed severe acute respiratory syndrome (SARS-CoV) type 2 virus to transmit the infection, which also explains the exponential increase in the number of COVID-19 cases globally. Furthermore, the rate of recovery from clinical COVID-19 in certain pockets of the globe is surprisingly high. Based on published reports and available literature, here, we speculated a few immunovirological mechanisms as to why a vast majority of individuals remain asymptomatic similar to exotic animal (bats and pangolins) reservoirs that remain refractile to disease development despite carrying a huge load of diverse insidious viral species, and whether such evolutionary advantage would unveil therapeutic strategies against COVID-19 infection in humans. Understanding the unique mechanisms that exotic animal species employ to achieve viral control, as well as inflammatory regulation, appears to hold key clues to the development of therapeutic versatility against COVID-19.
  4. Velu V, Banerjee S, Radhakrishnan V, Gupta G, Chellappan DK, Fuloria NK, et al.
    PMID: 33573582 DOI: 10.2174/1871523020666210126144506
    AIMS: The present investigation was aimed at exploring the phytoconstituents using Gas Chromatography Mass Spectroscopy and to evaluate antioxidant and anti-inflammatory properties of the leaf extracts.

    MATERIALS AND METHODS: The extracts were obtained sequentially with petroleum ether, ethyl acetate and water using Soxhlet apparatus. The anti-inflammatory property of the identified compounds using GC- MS spectroscopy was evaluated in silico. The antioxidant activity was performed by DPPH and H2O2 method whereas anti-inflammatory study was carried out by HRBC membrane stabilization method. Terpenoids were found to be a major constituents in petroleum ether extract while, phenols and flavonoids were predominantly found in ethyl acetate extract.

    RESULTS AND DISCUSSION: The GC-MS analysis of the extract revealed six major molecules including Squalene, 19β, 28-epoxyleanan-3-ol and 2-tu-Butyl-5-chloromethyl-3-methyl-4-oxoimidazolidine- 1-carboxylic acid. The ethyl acetate extract showed a significant antioxidant activity (P<0.01) in both DPPH method (70.87%) and H2O2 method (73.58%) at 200 μg mL-1. Increased membrane stabilization of petroleum ether extract was observed in the in vitro anti-inflammatory activity study. A strong relationship between the terpenoid content and anti-inflammatory activity was obtained from the correlation (0.971) and docking study.

    CONCLUSION: These results justify T. involucrata to be a rich source of terpenoids with potent anti- inflammatory property.

  5. Wong SW, Ting YW, Yong YK, Tan HY, Barathan M, Riazalhosseini B, et al.
    Scand J Clin Lab Invest, 2021 Apr;81(2):147-159.
    PMID: 33528280 DOI: 10.1080/00365513.2021.1876245
    The pathogenesis involving non-alcoholic fatty liver disease (NAFLD) in the context of chronic HBV (CHB) virus infection requires to be understood for developing improved modalities of diagnosis and treatment. We retrospectively investigated the association between NAFLD and CHB virus infection in the context of liver fibrosis. Among the 522 consecutive CHB patients who underwent transient elastography between years 2013 and 2016, we studied 455 subjects in the current investigation. Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) scores were generally higher in patients with steatosis and fibrosis or cirrhosis. Antiviral treatment had significantly reduced the hepatitis B virus (HBV) viral load. Other liver function markers showed a significant positive correlation with both CAP and LSM scores. Plasma IL-13 was independently associated with increased CAP score where every increase of 1 unit of IL-13 was associated with an increase in CAP score by 0.98 unit. CCL11 was independently associated with LSM with every increase of CCL11 by a unit that, in turn, was associated with an increase of LSM score. We found that there was a high concurrence of NAFLD among patients with CHB virus infection. The presence of metabolic syndrome and chronic inflammation in CHB virus-infected patients were two independent factors that led to the progression of liver cirrhosis, with IL-13 playing the key role in linking the metabolic with the inflammatory components.
  6. Selvavinayagam ST, Aswathy B, Yong YK, Frederick A, Murali L, Kalaivani V, et al.
    PLOS Glob Public Health, 2023;3(11):e0002327.
    PMID: 37992019 DOI: 10.1371/journal.pgph.0002327
    Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy. The study investigates whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. The plasma cytokines were measured using a commercial Bio-Plex Pro Human Cytokine 17-plex assay. Increased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold. Our study suggests that CXCL-8 and MCP-1 could serve as the surrogate biomarkers of LTBI, particularly in resource-limited settings. Further laboratory investigations are warranted before extrapolating CXCL8 and MCP-1 for their usefulness as surrogate biomarkers of LTBI in resource-limited settings.
  7. Selvavinayagam ST, Karishma SJ, Hemashree K, Yong YK, Suvaithenamudhan S, Rajeshkumar M, et al.
    PMID: 38076717 DOI: 10.1016/j.lansea.2023.100272
    BACKGROUND: Despite the continued vaccination efforts, there had been a surge in breakthrough infections, and the emergence of the B.1.1.529 omicron variant of SARS-CoV-2 in India. There is a paucity of information globally on the role of newer XBB variants in community transmission. Here, we investigated the mutational patterns among hospitalised patients infected with the XBB omicron sub-variant, and checked if there was any association between the rise in the number of COVID-19 cases and the observed novel mutations in Tamil Nadu, India.

    METHODS: Nasopharyngeal and oropharyngeal swabs, collected from symptomatic and asymptomatic COVID-19 patients were subjected to real-time PCR followed by Next Generation Sequencing (NGS) to rule out the ambiguity of mutations in viruses isolated from the patients (n = 98). Using the phylogenetic association, the mutational patterns were used to corroborate clinico-demographic characteristics and disease severity among the patients.

    FINDINGS: Overall, we identified 43 mutations in the S gene across 98 sequences, of which two were novel mutations (A27S and T747I) that have not been reported previously with XBB sub-variants in the available literature. Additionally, the XBB sequences from our cohort had more mutations than omicron B.1.1.529. The phylogenetic analysis comprising six major branches clearly showed convergent evolution of XBB. Our data suggests that age, and underlying conditions (e.g., diabetes, hypertension, and cardiovascular disease) or secondary complications confers increased susceptibility to infection rather than vaccination status or prior exposure. Many vaccinated individuals showed evidence of a breakthrough infection, with XBB.3 being the predominant variant identified in the study population.

    INTERPRETATION: Our study indicates that the XBB variant is highly evasive from available vaccines and may be more transmissible, and potentially could emerge as the 'next' predominant variant, which likely could overwhelm the existing variants of SARS-CoV-2 omicron variants.

    FUNDING: National Health Mission (India), SIDASARC, VINNMER (Sweden), ORIP/NIH (USA).

  8. Selvavinayagam ST, Suvaithenamudhan S, Yong YK, Hemashree K, Rajeshkumar M, Kumaresan A, et al.
    J Med Virol, 2024 Feb;96(2):e29456.
    PMID: 38329187 DOI: 10.1002/jmv.29456
    A state-wide prospective longitudinal investigation of the genomic surveillance of the omicron B.1.1.529 SARS-CoV-2 variant and its sublineages in Tamil Nadu, India, was conducted between December 2021 and March 2023. The study aimed to elucidate their mutational patterns and their genetic interrelationship in the Indian population. The study identified several unique mutations at different time-points, which likely could attribute to the changing disease characteristics, transmission, and pathogenicity attributes of omicron variants. The study found that the omicron variant is highly competent in its mutating potentials, and that it continues to evolve in the general population, likely escaping from natural as well as vaccine-induced immune responses. Our findings suggest that continuous surveillance of viral variants at the global scenario is warranted to undertake intervention measures against potentially precarious SARS-CoV-2 variants and their evolution.
  9. Selvavinayagam ST, Aswathy B, Yong YK, Frederick A, Murali L, Kalaivani V, et al.
    medRxiv, 2023 Aug 09.
    PMID: 37609153 DOI: 10.1101/2023.08.07.23293767
    BACKGROUND: Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy.

    METHODS: We investigated whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. We also measured the plasma cytokines using a commercial Bio-Plex Pro Human Cytokine 17-plex assay.

    RESULTS: Increased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold.

    CONCLUSIONS: We postulated that CXCL8 and MCP-1 could be the surrogate biomarkers of LTBI, especially in resource-limited settings.

  10. Selvavinayagam ST, Sankar S, Yong YK, Murugesan A, Suvaithenamudhan S, Hemashree K, et al.
    medRxiv, 2024 Apr 19.
    PMID: 38699322 DOI: 10.1101/2024.04.16.24305882
    In December 2023, we observed a notable shift in the COVID-19 landscape, when the JN.1 emerged as a predominant SARS-CoV-2 variant with a 95% incidence. We characterized the clinical profile, and genetic changes in JN.1, an emerging SARS-CoV-2 variant of interest. Whole genome sequencing was performed on SARS-CoV-2 positive samples, followed by sequence analysis. Mutations within the spike protein sequences were analyzed and compared with the previous lineages and sublineages of SARS-CoV-2, to identify the potential impact of these unique mutations on protein structure and possible functionality. Several unique and dynamic mutations were identified herein. Our data provides key insights into the emergence of newer variants of SARS-CoV-2 in our region and highlights the need for robust and sustained genomic surveillance of SARS-CoV-2.
  11. Shankar EM, Velu V, Vignesh R, Vijayaraghavalu S, Rukumani DV, Sabet NS
    Microbiol. Immunol., 2012 Aug;56(8):497-505.
    PMID: 22900503 DOI: 10.1111/j.1348-0421.2012.00485.x
    Early defence mechanisms of innate immunity respond rapidly to infection against HIV-1 in the genital mucosa. Additionally, innate immunity optimises effective adaptive immune responses against persistent HIV infection. Recent research has highlighted the intrinsic roles of apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G, tripartite motif-containing protein 5, tetherin, sterile α-motif and histidine/aspartic acid domain-containing protein 1 in restricting HIV-1 replication. Likewise, certain endogenously secreted antimicrobial peptides, namely α/β/θ-defensins, lactoferrins, secretory leukocyte protease inhibitor, trappin-2/elafin and macrophage inflammatory protein-3α are reportedly protective. Whilst certain factors directly inhibit HIV, others can be permissive. Interferon-λ3 exerts an anti-HIV function by activating Janus kinase-signal transducer and activator of transcription-mediated innate responses. Morphine has been found to impair intracellular innate immunity, contributing to HIV establishment in macrophages. Interestingly, protegrin-1 could be used therapeutically to inhibit early HIV-1 establishment. Moreover, chloroquine inhibits plasmacytoid dendritic cell activation and improves effective T-cell responses. This minireview summarizes the recently identified targets for innate immunity-mediated therapies and outlines the challenges that lie ahead in improving treatment of HIV infection.
  12. Ansari AW, Ahmad F, Shankar EM, Kong YY, Tan HY, Jacobs R, et al.
    PMID: 32398557 DOI: 10.1097/QAI.0000000000002399
    BACKGROUND: We have previously shown an association of elevated co-inhibitory molecule 2B4 expression with iNKT cells alterations in HIV disease. Herein we show a comparative analysis of 2B4 expression on iNKT cells of HIV long-term non-progressors (LTNPs) and progressors.

    METHODS: Anti-retroviral therapy (ART) naïve HIV-seropositive individuals (progressors, n=16) and long-term non-progressors (LTNPs, n=10) were recruited for this study. We employed multi-color flow cytometry on frozen peripheral blood mononuclear cells (PBMCs) to determine iNKT subset frequencies, the levels of co-inhibitory 2B4 expression, and intracellular IFN-γ production. CD1d tetramer was used to characterize iNKT cells.

    RESULTS: We report significantly lower level of 2B4 expression on bulk LTNPs iNKT cells as well as on their CD4 subsets compared to HIV progressors. Furthermore, the iNKT cells from LTNPs produced higher amount of IFN-γ than HIV progressors as detected by intracellular cytokine staining. Interestingly, the frequency of 2B4iNKT cells of progressors but not LTNPs significantly correlates with CD4 T cell count, HIV viral load and IFNγ production by iNKT cells.

    CONCLUSION: Our results suggest that in addition to suppressed HIV replication, diminished 2B4 expression and associated co-inhibitory signaling, and substantial production of IFN-γ could contribute to preserved iNKT cell phenotype in LTNPs.

  13. Barathan M, Gopal K, Mohamed R, Ellegård R, Saeidi A, Vadivelu J, et al.
    Apoptosis, 2015 Apr;20(4):466-80.
    PMID: 25577277 DOI: 10.1007/s10495-014-1084-y
    Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(®) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.
  14. Saeidi A, Buggert M, Che KF, Kong YY, Velu V, Larsson M, et al.
    Cell Immunol, 2015 Nov-Dec;298(1-2):126-33.
    PMID: 26520669 DOI: 10.1016/j.cellimm.2015.10.009
    Understanding the mechanisms involved in cellular immune responses against control of human immunodeficiency virus (HIV) infection is key to development of effective immunotherapeutic strategies against viral proliferation. Clear insights into the regulation of cytotoxic CD8+ T cells is crucial to development of effective immunotherapeutic strategies due to their unique ability to eliminate virus-infected cells during the course of infection. Here, we reviewed the roles of transcription factors, co-inhibitory molecules and regulatory cytokines following HIV infection and their potential significance in regulating the cytotoxic potentials of CD8+ T cells.
  15. Saeidi A, Chong YK, Yong YK, Tan HY, Barathan M, Rajarajeswaran J, et al.
    Cell Immunol, 2015 Sep;297(1):19-32.
    PMID: 26071876 DOI: 10.1016/j.cellimm.2015.05.005
    The role of T-cell immunosenescence and functional CD8(+) T-cell responses in HIV/TB co-infection is unclear. We examined and correlated surrogate markers of HIV disease progression with immune activation, immunosenescence and differentiation using T-cell pools of HIV/TB co-infected, HIV-infected and healthy controls. Our investigations showed increased plasma viremia and reduced CD4/CD8 T-cell ratio in HIV/TB co-infected subjects relative to HIV-infected, and also a closer association with changes in the expression of CD38, a cyclic ADP ribose hydrolase and CD57, which were consistently expressed on late-senescent CD8(+) T cells. Up-regulation of CD57 and CD38 were directly proportional to lack of co-stimulatory markers on CD8(+) T cells, besides diminished expression of CD127 (IL-7Rα) on CD57(+)CD4(+) T cells. Notably, intracellular IFN-γ, perforin and granzyme B levels in HIV-specific CD8(+) T cells of HIV/TB co-infected subjects were diminished. Intracellular CD57 levels in HIV gag p24-specific CD8(+) T cells were significantly increased in HIV/TB co-infection. We suggest that HIV-TB co-infection contributes to senescence associated with chronic immune activation, which could be due to functional insufficiency of CD8(+) T cells.
  16. Saeidi A, Tien Tien VL, Al-Batran R, Al-Darraji HA, Tan HY, Yong YK, et al.
    PLoS One, 2015;10(4):e0124659.
    PMID: 25894562 DOI: 10.1371/journal.pone.0124659
    Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved antimicrobial MR1-restricted CD8(+) T cells co-expressing the semi-invariant TCR Vα7.2, and are numerous in the blood and mucosal tissues of humans. MAIT cells appear to undergo exhaustion in chronic viral infections. However, their role in human immunodeficiency virus type 1 (HIV-1) mono-infection and HIV/tuberculosis (TB) co-infection have seldom been elaborately investigated. We conducted a cross-sectional study to investigate the frequencies and phenotypes of CD161(++)CD8(+) T cells among anti-retroviral therapy (ART)/anti-TB therapy (ATT) treatment-naïve HIV/TB co-infected, ART/TB treated HIV/TB co-infected, ART naïve HIV-infected, ART-treated HIV-infected patients, and HIV negative healthy controls (HCs) by flow cytometry. Our data revealed that the frequency of MAIT cells was severely depleted in HIV mono- and HIV/TB co-infections. Further, PD-1 expression on MAIT cells was significantly increased in HIV mono- and HIV-TB co-infected patients. The frequency of MAIT cells did not show any significant increase despite the initiation of ART and/or ATT. Majority of the MAIT cells in HCs showed a significant increase in CCR6 expression as compared to HIV/TB co-infections. No marked difference was seen with expressions of chemokine co-receptor CCR5 and CD103 among the study groups. Decrease of CCR6 expression appears to explain why HIV-infected patients display weakened mucosal immune responses.
  17. Yong YK, Saeidi A, Tan HY, Rosmawati M, Enström PF, Batran RA, et al.
    Front Immunol, 2018;9:472.
    PMID: 29616020 DOI: 10.3389/fimmu.2018.00472
    Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.
  18. Yong YK, Tan HY, Saeidi A, Rosmawati M, Atiya N, Ansari AW, et al.
    Innate Immun, 2017 07;23(5):459-467.
    PMID: 28606013 DOI: 10.1177/1753425917714854
    Hepatitis B virus (HBV) infection is a major cause of chronic liver disease that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses represent the key determinants of HBV clearance or persistence. Here, we investigated the role of the early activation marker, CD69 and effector cytokines, granzyme B (GrB) and IFN-γ in the exhaustion of innate-like TCR Vα7.2+CD4+T cells, in 15 individuals with chronic HBV (CHB) infection where six were HBV DNA+ and nine were HBV DNA-. The percentage of cytokine-producing T cells and MAIT cells were significantly perturbed in HBV patients relative to healthy controls (HCs). The intracellular expression of GrB and IFN-γ was significantly reduced in MAIT cells derived from HBV-infected patients as compared to HCs, and the levels correlated with the percentage and levels [mean fluorescence intensity (MFI)] of CD69 expression. The total expression of CD69 (iMFI) was lower in CHB patients as compared to HCs. The frequency of CD69+ cells correlated with the levels of cytokine expression (MFI), particularly in CHB patients as compared to HCs. In summary, the polyfunctionality of peripheral T cells was significantly reduced among CHB patients, especially in the TCR Vα7.2+CD4+T cells, and the levels of cytokine expression correlated with functional cytokine levels.
  19. Barathan M, Mohamed R, Vadivelu J, Chang LY, Vignesh R, Krishnan J, et al.
    Cell Immunol, 2017 03;313:1-9.
    PMID: 28104239 DOI: 10.1016/j.cellimm.2016.12.002
    Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide-stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-β1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-α, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence.
  20. Yong YK, Tan HY, Saeidi A, Wong WF, Vignesh R, Velu V, et al.
    Front Microbiol, 2019;10:2789.
    PMID: 31921004 DOI: 10.3389/fmicb.2019.02789
    Tuberculosis (TB) treatment monitoring is paramount to clinical decision-making and the host biomarkers appears to play a significant role. The currently available diagnostic technology for TB detection is inadequate. Although GeneXpert detects total DNA present in the sample regardless live or dead bacilli present in clinical samples, all the commercial tests available thus far have low sensitivity. Humoral responses against Mycobacterium tuberculosis (Mtb) antigens are generally low, which precludes the use of serological tests for TB diagnosis, prognosis, and treatment monitoring. Mtb-specific CD4+ T cells correlate with Mtb antigen/bacilli burden and hence might serve as good biomarkers for monitoring treatment progress. Omics-based techniques are capable of providing a more holistic picture for disease mechanisms and are more accurate in predicting TB disease outcomes. The current review aims to discuss some of the recent advances on TB biomarkers, particularly host biomarkers that have the potential to diagnose and differentiate active TB and LTBI as well as their use in disease prognosis and treatment monitoring.
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