Interferon Gamma and Soluble MICA as A New Biomarker for Immunological Severity Detection in HIV Infected Patients Undergoing Retroviral Therapy
Abstract
Objective: Variations in immune responses to viral particles and antiretroviral drugs show interference of the cluster of differentiation number 4 T cell monitoring methods, leading to an inaccurate evaluation for human immunodeficiency virus infected patients receiving antiretroviral therapy. Other biological markers; such as cytokine; especially interferon gamma (IFN-γ) and soluble molecules of major histocompatibility complex class I chain related molecule A (sMICA), were designed as a novel severity marker.
Material and Methods: Levels of IFN-γ and sMICA were evaluated for 69 patients, who presented with HIV infection; with no other diseases or inflammation. The candidates were classified into four groups, depending on their CD4 T cell count. The IFN-γ and sMICA serum content of the patients was detected in triplicate, using enzyme-linked immunosorbent assay.
Results: Mean value of IFN-γ in each severity group was 49.1±9.7, 69.1±21.8, 63.0±12.8, and 69.4±18.4 picograms/ milliliter for none, mild, advanced, and severe cases, respectively. sMICA was detected at 36.8±19.6, 134.7±122.5, 33.6±12.4, and 83.9±40.0 international unit/milliliter, respectively. A significant association between IFN-γ and CD4 cells of normal anti-retroviral treatment response, defined by CD4 cells and viral loads, was observed using Spearman correlation, with p-values 0.033, r -0.434, 0.026 and -0.321, respectively.
Conclusion: IFN-γ and sMICA were found to be associated with the CD4 count in the normal responses to antiretroviral treatment. This suggested that IFN-γ could be used as a biological marker for monitoring of immunological severity during anti-retroviral responses.
Keywords
Full Text:
PDFReferences
Lodi S, Fisher M, Phillips A, De Luca A, Ghosn J, Malyuta R, et al. Symptomatic illness and low CD4 cell count at HIV seroconversion as markers of severe primary HIV infection. PLoS One 2013;14:8.
Highleyman L. Inflammation, immune activation, and HIV. Winter-Spring 2010;22:12-26.
Catalfamo M, Le Saout C, Lane HC. The role of cytokines in the pathogenesis and treatment of HIV infection. Cytokine Growth Factor Rev 2012;23:207-14.
Satyakiran GV, Bavle RM, Alexander G, Rao S, Venugopal R, Hosthor SS. A relationship between CD4 count and oral manifestations of human immunodeficiency virus-infected patients on highly active antiretroviral therapy in urban population. J Oral Maxillofac Pathol 2016;20:419-26.
Hamanishi J, Mandai M, Matsumura N, Abiko K, Baba T, Konishi I. PD-1/PD-L1 blockade in cancer treatment: perspectives and issues. Int J Clin Oncol 2016;21:462-73.
Song Y, Zhuang Y, Zhai S, Huang D, Zhang Y, Kang W, et al. Increased expression of TLR7 in CD8(+) T cells leads to TLR7- mediated activation and accessory cell-dependent IFNgamma production in HIV type 1 infection. AIDS Res Hum Retroviruses 2009;25:1287-95.
Munhoz LGC, Garcia Spina F, Machado DM, Gouvea A, Succi RCM, Diaz RS, et al. Prolonged Antiretroviral Therapy in Adolescents With Vertical HIV Infection Leads to Different Cytokine Profiles Depending on Viremia Persistence. Pediatr Infect Dis J 2019;38:1115-20.
Yue FY, Cohen JC, Ho M, Rahman AKMN, Liu J, Mujib S, et al. HIV-Specific Granzyme B-Secreting but Not Gamma Interferon-Secreting T Cells Are Associated with Reduced Viral Reservoirs in Early HIV Infection. J Virol 2017;91:e02233-16.
Schlenke P, Tapernon K, Ahlke C, Mertens A, Sibrowski W. The Impact of the German Tissue Act on the Manufacturing of Autologous and Allogeneic Stem Cell Preparations. Transfus Med Hemother 2008;35:446-52.
Leal FE, Premeaux TA, Abdel-Mohsen M, Ndhlovu LC. Role of Natural Killer Cells in HIV-Associated Malignancies. Front Immunol 2017;8:315.
Weiss ID, Wald O, Wald H, Beider K, Abraham M, Galun E, et al. IFN-gamma treatment at early stages of influenza virus infection protects mice from death in a NK cell-dependent manner. J Interferon Cytokine Res 2010;30:439-49.
Mikulak J, Oriolo F, Zaghi E, DI Vito C, Mavilio D. Natural killer cells in HIV-1 infection and therapy. Aids 2017;31:2317-30.
Jiang Y, Zhou F, Tian Y, Zhang Z, Kuang R, Liu J, et al. Higher NK cell IFN-γ production is associated with delayed HIV disease progression in LTNPs. J Clin Immunol 2013;33:1376- 85.
Pai M, Denkinger CM, Kik SV, Rangaka MX, Zwerling A, Oxlade O, et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev 2014;27:3-20.
Department of Diseases control. Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2017. Bangkok: Co-opthai Press; 2017.
World Health Organization. WHO Case definition of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. Geneva: WHO; 2007.
Patrikar S, Basannar DR, Bhatti VK, Kotwal A, Gupta RM, Grewal RS. Rate of decline in CD4 count in HIV patients not on antiretroviral therapy. Med J Armed Forces India 2014;70: 134-8.
Rareongjai S, Pongtassanaham O. Genetically Association of Duffy Blood Groups Antigens in HIV Infection and Severity. Srinagarind Med J 2018;33:301-7.
Watanabe D, Uehira T, Suzuki S, Matsumoto E, Ueji T, Hirota K, et al. Clinical characteristics of HIV-1-infected patients with high levels of plasma interferon-γ: a multicenter observational study. BMC Infect Dis 2019;19:11.
Zhang QW, Song JY, Yu JH, Sun MZ, Tang SY, Yang SZ, et al. Polymorphism of IFN-γ +874T/A associated with production of IFN-γ affects human papillomavirus susceptibility in rural women from Luohe, Henan, China. Onco Targets Ther 2018; 11:4339-44.
Rao PV, Ramanavelan S, Rajasekaran S, Raja A. Natural-killer cell-derived cytolytic molecules in HIV-associated pulmonary tuberculosis-role of exogenous interleukins. J Clin Immunol 2010;30:393-401.
Schoenborn JR, Wilson CB. Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol 2007;96:41-101.
de Jager W, Bourcier K, Rijkers GT, Prakken BJ, Seyfert-Margolis V. Prerequisites for cytokine measurements in clinical trials with multiplex immunoassays. BMC Immunol 2009;10:52.
Chettimada S, Lorenz DR, Misra V, Dillon ST, Reeves RK, Manickam C, et.al. Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy. Sci Rep 2018;8:7227.
Mercurio V, Fitzgerald W, Molodtsov I, Margolis L. Persistent Immune Activation in HIV-1-Infected Ex Vivo Model Tissues Subjected to Antiretroviral Therapy: Soluble and Extracellular Vesicle-Associated Cytokines. J Acquir Immune Defic Syndr 2020;84:45-53.
Sun J, Zhao Y, Peng Y, Han Z, Liu G, Qin L, et al. Multiple T-cell responses are associated with better control of acute HIV-1 infection: An observational study. Medicine (Baltimore) 2016;95:e4429.
Mahmoud Sadeghi, Caner Süsal, Volker Daniel, Cord Naujokat, Rainer Zimmermann, Angela Huth-Kühne, Gerhard Opelz. Short communication: decreasing soluble CD30 and increasing IFN-gamma plasma levels are indicators of effective highly active antiretroviral therapy. AIDS Res Hum Retroviruses 2007;23:886-90.
J Vecchiet, M Dalessandro, F Travasi, K Falasca, A Di Iorio, C Schiavone, P Zingariello, E Di Ilio, E Pizzigallo, R Paganelli. Interleukin-4 and interferon-gamma production during HIV-1 infection and changes induced by antiretroviral therapy. Int J Immunopathol Pharmacol 2003;16:157-66.
Yunhai Y, Yan L, Yan H, Yuhuang Zh, Quan Zh, Huaying Zh, et al. The effect of a year of highly active antiretroviral therapy on immune reconstruction and cytokines in HIV/AIDS patients. AIDS Res Hum Retroviruses 2013;29:691-7.
Erica G, Lia V, Silvia DC, Vincenzo M, Maria GD, Massimo A, et al. NK cells of HIV-1-infected patients with poor CD4 + T-cell reconstitution despite suppressive HAART show reduced IFN-γ production and high frequency of autoreactive CD56 bright cells. Immunol Lett 2017;190:185-93.
Lee S, Hirohama M, Noguchi M, Nagata K, Kawaguchi A. Influenza A Virus Infection Triggers Pyroptosis and Apoptosis of Respiratory Epithelial Cells through the Type I Interferon Signaling Pathway in a Mutually Exclusive Manner. J Virol 2018;92:1-11.
Leal FE, Premeaux TA, Abdel-Mohsen M, Ndhlovu LC. Role of Natural Killer Cells in HIV-Associated Malignancies. Front Immunol 2017;8:315.
Mahoney KM, Freeman GJ, McDermott DF. The Next ImmuneCheckpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma. Clin Ther 2015;37:764-82.
Rodríguez-García M, Porichis F, de Jong OG, Levi K, Diefenbach TJ, Lifson JD, et al. Expression of PD-L1 and PD-L2 on human macrophages is up-regulated by HIV-1 and differentially modulated by IL-10. J Leukoc Biol 2011;89:507- 15.
Zingoni A, Vulpis E, Cecere F, Amendola MG, Fuerst D, Saribekyan T, et al. MICA-129 Dimorphism and Soluble MICA Are Associated With the Progression of Multiple Myeloma. Front Immunol 2018;9:926.
Onyeaghala G, Lane J, Pankratz N, Nelson HH, Thyagarajan B, Walcheck B, et al. Association between MICA polymorphisms, s-MICA levels, and pancreatic cancer risk in a populationbased case-control study. PLoS ONE 2019;14:e0217868.
Yanyan X, Nicole Sh Jie L, Wei L, Sushmita R, Samir KG, et al. MMPs/TIMPs imbalances in the peripheral blood and cerebrospinal fluid are associated with the pathogenesis of HIV-1- associated neurocognitive disorders. Brain Behav Immun 2017;65:161-72.
Li L, Dufour AP. Using IFN-gamma as a biomarker for detecting exposure to viral pathogens. Curr Microbiol 2008; 56:84-8.
Aichelburg MC, Tittes J, Breitenecker F, Reiberger T, Kohrgruber N, Rieger A. Prognostic value of indeterminate IFN-γ release assay results in HIV-1 infection. J Clin Microbiol 2012;50: 2767-9.
Dhillon NK, Murphy WJ, Filla MB, Crespo AJ, Latham HA, O'Brien-Ladner A. Down modulation of IFN-gamma signaling in alveolar macrophages isolated from smokers. Toxicol Appl Pharmacol 2009;237:22-8.
Refbacks
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.