Difference in Markers of Microbial Translocation and Cell Apoptosis in HIV Monoinfected and HIV/HCV Coinfected Patients

Madelāne, Monta; Krūmiņa, Angelika; Sīmanis, Raimonds; Šķenders, Ģirts; Ivanovs, Andrejs; Stūre, Gunta; Vīksna, Ludmila

doi:10.2478/prolas-2019-0048

Abstract

Immune activation in human immunodeficiency virus (HIV) infection is driven by microbial translocation and in HIV patients is one of the contributors to faster progression of liver disease along with increased cell apoptosis. The aim of the study was to compare microbial translocation and apoptosis markers in HIV monoinfected and HIV/hepatitis C virus (HCV) coinfected patients, depending on HIV immune status and antiretroviral treatment (ART). We analysed data for 78 HIV monoinfected and 105 HIV/HCV coinfected patients from the Rīga East University Hospital. Lipopolysaccharide (LPS), endotoxin core antibodies (EndoCAb), cytokeratin 18 (CK18) and cyto-chrome c (Cyt-c) levels were measured. No significant difference in LPS, EndoCAb, Cyt-c levels between HIV and HIV/HCV patients was found. The CK18 level was higher in the HIV/HCV group. Correlation between CD4+ cell count and EndoCAb antibodies was found in HCV positive patients. There was a significant effect of ART on markers for EndoCAb IgA and EndoCAb IgM antibodies in the HIV monoinfected group. Correlation between CD4+ cell count and EndoCAb antibodies and LPS was found in HIV/HCV patients on ART. Coinfection with HCV can lead to more pronounced response in EndoCAb antibody production and higher levels of cell apoptosis markers, despite similar LPS levels. ART has a positive effect on immune activation.

References

Abad-Fernandez, M., Vallejo, A., Hernandez-Novoa, B., Diaz, L., Gutierrez, C., Madrid, N., Angeles Munoz, M., Moreno, S. (2013). Correlation between different methods to measure microbial translocation and its association with immune activation in long-term supressed HIV-1 infected individuals. J. Acquir. Immune Defic. Syndr., 64, 149–153.10.1097/QAI.0b013e31829a2f1224047967
Search in Google Scholar Back to article
Albillos, A., de la Hera, A., Gonzalez, M., Moya, J.-L., Calleja, J.-L., Monserrat, J., Riuz-del-Arbol, L., Alvarez-Mon, M. (2003). Increased lipopolysaccharide binding protein in cirrhotic patients with marked immune and hemodynamic derangement. Hepatology, 37 (1), 208–217.10.1053/jhep.2003.5003812500206
Search in Google Scholar Back to article
Balagopal, A., Phil, F. H., Astemborski, J., Block, T. M., Mehta, A., Long, R., Kirk, G. D., Mehta, S. H., Cox, A. L., Thomas, D. L., Ray, S. C. (2008). Human immunodeficiency virus-related microbial translocation and progression of hepatitis C. Gastroenterology, 135 (1), 226–233.10.1053/j.gastro.2008.03.022264490318457674
Search in Google Scholar Back to article
Balagopal, A., Gama, L., Franco, V., Russell, J. N., Quinn, J., Higgins, Y., Smeaton, L. M., Clements, J. E., Thomas, D. L., Gupta, A. (2012). Detection of microbial translocation in HIV and SIV infection using the Limulus amebocyte lysate assay is masked by serum and plasma. PLoS ONE, 7 (8), 1–8.10.1371/journal.pone.0041258340985222870212
Search in Google Scholar Back to article
Brenchley, J. M., Price, D. A., Schacker, T. W., Asher, T. E., Silvestri, G., Rao, S., Kazzaz, Z., Bornstein, E., Lambotte, O., Altmann, D., Blazar, B. R., Rodriguez, B., Teixeira-Johnson, L., Landay, A., Martin, J. N., Hecht, F. M., Picker, L. J., Lederman, M. M., Deeks, S. G., Douek, D. C. (2006). Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nature Med., 12, 1365–1371.10.1038/nm151117115046
Search in Google Scholar Back to article
Caradonna, L., Mastronardi, M. L., Magrone, T., Cozzolongo, R., Cuppone, R., Manghisi, O. G., Caccavo, D., Pellegrino, N. M., Amoroso, A., Jirillo, E., Amati, L. (2002). Biological and clinical significance of entotoxemia in the course of hepatitis C virus infection. Curr. Pharmaceut. Des., 8, 995–1005.10.2174/138161202460698311945146
Search in Google Scholar Back to article
Chan, C. C., Hwang, S. J., Lee, F. Y., Wang, S. S., Chang, F. Y., Li, C. P., Chu, C. J., Lu, R. H., Lee, S. D. (1997). Prognostic value of plasma endotoxin levels in patients with cirrhosis. Scand. J. Gastroenterol., 32 (9), 942–945.10.3109/003655297090112069299675
Search in Google Scholar Back to article
Crane, M., Iser, D., Lewin, S. R. (2012). Human immunodeficiency virus infection and the liver. World J. Hepatol., 4 (3), 91–98.10.4254/wjh.v4.i3.91332149522489261
Search in Google Scholar Back to article
Dinh, D. M., Volpe, G. E., Duffalo, C., Bhalchandra, S., Tai, A. K., Kane, A. V., Wanke, C. A., Ward, H. D. (2015). Intestinal microbiota, microbial translocation, and systemic inflammation in chronic HIV infection. J. Infect. Dis., 211, 19–27.10.1093/infdis/jiu409432631625057045
Search in Google Scholar Back to article
Epeldegui, M., Magpantay, L., Guo, Y., Halec, G., Cumberland, W. G., Yen, P. K., Macatangay, B., Margolick, J. B., Fositch, A. F., Wolinsky, S., Martinez-Maza, O., Hussain, S. K. (2018). A prospective study of serum microbial translocation biomarkers and risk of AIDS- related non- Hodgkin lymphoma. AIDS, 32 (7), 945–954.10.1097/QAD.0000000000001771586910929424776
Search in Google Scholar Back to article
Epple, H.-J., Schneider, T., Troeger, H., Kunkel, D., Allers, K., Moos, V., Amasheh, M., Loddenkemper, C., Fromm, M., Zeitz, M., Schulzke, J.-D. (2009). Impairment of the intestinal barrier is evident in untreated but absent in suppressively treated HIV- infected patients. Gut, 58, 220–227.10.1136/gut.2008.15042518936106
Search in Google Scholar Back to article
French, A., Evans, C. T., Agniel, D. M., Cohen, M. H., Peters, M., Landay, A. L., Desai, S. N. (2013). Microbial translocation and liver disease progression in women coinfected with HIV and hepatitis C virus. J. Infect. Dis., 208, 679–689.10.1093/infdis/jit225371990723687224
Search in Google Scholar Back to article
Hansjee, N., Kaufmann, G. R., Strub, C., Weber, R., Battegay, M., Erb, P. (2004). Persistent apoptosis in HIV-1-infected individuals receiving potent antiretroviral therapy is associated with poor recovery of CD4 T lymphocytes. J. Acquir. Immune Defic. Syndr., 36, 671–677.10.1097/00126334-200406010-0000315167285
Search in Google Scholar Back to article
Hatano, H. (2013). Immune activation and HIV persistence: Considerations for novel therapeutic interventions. AIDS, 8 (3), 211–216.10.1097/COH.0b013e32835f9788404148823454864
Search in Google Scholar Back to article
Jiang, W., Lederman, M. M., Hunt, P., Sieg, S. F., Haley, K., Rodriguez, B., Landay, A., Martin, J., Sinclair, E., Asher, A. I., Deeks, S. G., Douek, D. C., Brenchley, J. M. (2009). Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. J. Infect. Dis., 199 (8), 1177–1185.10.1086/597476272862219265479
Search in Google Scholar Back to article
Jirillo, E., Amati, L., Caradonna, L., Greco, B., Cozzolongo, R., Cuppone, R., Piazzolla, G., Caccavo, D., Antonaci, S., Manghisi, O. G. (1998). Soluble (s) CD14 and plasmatic lipopolysaccharides (LPS) in patients with chronic hepatitis C before and after treatment with interferon (IFN)-α. Immunopharmacol. Immunotoxicol., 20 (1), 1–14.10.3109/089239798090348059543696
Search in Google Scholar Back to article
Kronenberger, B., von Wagner, M., Herrmann, E., Mihm, U., Piiper, A., Sarrazin, C., Zeuzem, S. (2005). Apoptotic cytokeratin 18 neoepitopes in serum of patients with chronic hepatitis C. J. Viral Hepat.,12, 307–314.10.1111/j.1365-2893.2005.00594.x15850472
Search in Google Scholar Back to article
Lopez-Cortes, L. F., Trujillo-Rodriguez, M., Baez-Palomo, A., Benmarzouk-Hidalgo, O. J., Dominguez-Molina, B., Milanes-Guisado, Y., Espinosa, N., Viciana, P., Gutierrez-Valencia, A. (2018). Eradication of hepatitis C virus (HCV) reduces immune activation, microbial trans-location, and the HIV DNA level in HIV/HCV-coinfected patients. J. Infect. Dis., 218 (4), 624–632.10.1093/infdis/jiy13629986086
Search in Google Scholar Back to article
Macias, J., Japon, M. A., Saez, C., Palacios, R. B., Mira, J. A., Garcia-Garcia, J. A., Merchante, N., Vergara, S., Lozano, F., Gomez-Mateos, J., Pineda, J. A. (2005). Increased hepatocyte Fas expression and apoptosis in HIV and hepatitis C virus infection. J. Infect. Dis., 192, 1566–1576.10.1086/49173616206071
Search in Google Scholar Back to article
Marchetti, G., Bellistri, G. M., Borghi, E., Tincati, C., Ferramosca, S., La Francesca, M., Morace, G., Gori, A., d`Arminio Monforte, A. (2008). Microbial translocation is associated with sustained failure in CD+ T-cell reconstitution in HIV-infected patients on long-term highly active anti-retroviral therapy. AIDS, 22, 2035–2044.10.1097/QAD.0b013e3283112d2918784466
Search in Google Scholar Back to article
Marchetti, G., Cozzi-Lepri, A., Merlini, E., Bellistri, G. M., Castagna, A., Galli, M., Verrucchi, G., Antinori, A., Costantini, A., Giacometti, A., di Caro, A., D’arminio Monforte, A. (2011). Microbial translocation predicts disease progression of HIV- infected antiretroviral- naïve patients with high CD4+ cell count. AIDS, 25, 1385–1394.10.1097/QAD.0b013e3283471d1021505312
Search in Google Scholar Back to article
Marchetti, G., Tincati, C., Silvestri, G. (2013). Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin. Microbiol. Rev., 26, 2–18.10.1128/CMR.00050-12355366823297256
Search in Google Scholar Back to article
Marquez, M., Romero-Cores, P., Montes-Oca, M., Martin-Aspas, A., Soto-Cardenas, M.-J., Guerrero, F., Fernandez-Gutierrez, C., Giron-Gonzalez, J.-A. (2015). Immune activation response in chronic HIV-infected patients: Influence of hepatitis C virus coinfection. PLoS ONE, 10 (3), 1–15.10.1371/journal.pone.0119568436159725775475
Search in Google Scholar Back to article
Marks, M. A., Rabkin, C. S., Engels, E. A., Busch, E., Kopp, W., Rager, H., Goedert, J. J., Chaturvedi, A. K. (2012). Markers of microbial translocation and risk of AIDS-related lymphoma. AIDS, 27, 469–474.10.1097/QAD.0b013e32835c133323169327
Search in Google Scholar Back to article
Mhawej, M.-J., Brunet-Francois, C., Fonteneau, R., Ernst, D., Ferre, V., Stan, G.-B., Raffi, F., Moog, C. H. (2009). Apoptosis characterizes immunological failure of HIV infected patients. Control Eng. Practice, 17, 798–804.10.1016/j.conengprac.2009.01.001
Search in Google Scholar Back to article
Nien, H.-C., Hsu, S.-J., Su, T.-H., Yang, P.-J., Sheu, J.-C., Wang, J.-T., Chow, L.-P., Chen, C.-L., Kao, J.-H., Yang, W.-S. (2017). High serum lipopolysaccharide-binding protein level in chronic hepatitis C viral infection is reduced by anti-viral treatments. PLoS ONE, 12 (1), 1–11.10.1371/journal.pone.0170028524920628107471
Search in Google Scholar Back to article
Novati, S., Sacchi, P., Cima, S., Zuccaro, V., Columpsi, P., Pagani, L., Filice, G., Bruno, R. (2015). General issues on microbial translocation in HIV-infected patients. Eur. Rev. Med. Pharmacol. Sci,, 19, 866–878.
Search in Google Scholar Back to article
de Oliveira Pinto, L. M., Lecoeur, H., Ledru, E., Rapp, C., Patey, O., Gougeon, M.-L. (2002). Lack of control of T cell apoptosis under HAART. Influence of therapy regimen in vivo and in vitro. AIDS, 16, 329–339.10.1097/00002030-200202150-0000311834943
Search in Google Scholar Back to article
Parfieniuk-Kowerda, A., Lapinski T. W., Rogalska-Plonska, M., Swiderska, M., Panasiuk, A., Jaroszewicz, J., Flisika, R. (2013). Serum cytochrome c and m30-neoepitope of cytokeratin-18 in chronic hepatitis C. Liver Int., 34, 544–550.10.1111/liv.1229723981197
Search in Google Scholar Back to article
Roger, P.-M., Breittmayer, J.-P., Durant, J., Sanderson, F., Ceppi, C., Brignone, C., Cua, E., Clevenbergh, P., Fuzibet, J.-G., Pesce, A., Bernard, A., Dellamonica, P. (2002). Early CD4+ T cell recovery in human immunodeficiency virus-infected patients receiving effective therapy is related to a down-regulation of apoptosis and not to proliferation. J. Infect. Dis.,185, 463–470.10.1086/33857311865398
Search in Google Scholar Back to article
Rohrbach, J., Stickel, F., Schmid, P., Thormann, W., Kovari, H., Scherrer, A., Gunthard, H. F., Vuichard, D., Cavassini, M., Ambrosioni, J., Bernasconi, E., Furrer, H., Rauch, A. (2013). Changes in biomarkers of liver disease during successful combination antiretroviral therapy in HIV-HCV-coinfected individuals. Antiviral Ther., 19, 149–159.10.3851/IMP268624036684
Search in Google Scholar Back to article
Sandler, N. G., Wand, H., Roque, A., Law, M., Nason, M. C., Nixon, D. E., Pedersen, C., Ruxrungtham, K., Lewin, S. R., Emery, S., Neaton, J. D., Brenchley, J. M., Deeks, S. G., Sereti, I., Douek, D. C. (2011). Plasma levels of soluble CD14 independently predict mortality in HIV patients. J. Infect. Dis.,203, 780–790.10.1093/infdis/jiq118307112721252259
Search in Google Scholar Back to article
Sandler, N. G., Douek, D. C. (2012). Microbial translocation in HIV infection: Causes, consequences and treatment opportunities. Nature Rev. Microbiol., 10, 655–666.10.1038/nrmicro284822886237
Search in Google Scholar Back to article
Seidel, N., Volkmann, X., Langer, F., Flemming, P., Manns, M. P., Schulze-Osthoff, K., Bantel, H. (2005). The extent of liver steatosis in chronic hepatitis C virus infection is mirrored by caspase activity in serum. Hepatology, 42, 113–120.10.1002/hep.2074715920717
Search in Google Scholar Back to article
Vassallo, M., Mercie, P., Cottalorda, J., Ticchioni, M., Dellamonica, P. (2012). The role of lipopolysaccharide as a marker of immune activation in HIV-1 infected patients: A systematic literature review. Virology J., 9 (174), 1–8.10.1186/1743-422X-9-174349584822925532
Search in Google Scholar Back to article

Difference in Markers of Microbial Translocation and Cell Apoptosis in HIV Monoinfected and HIV/HCV Coinfected Patients

Abstract

Paradigm

My account