Mycobacterial antibody levels and immune restoration disease in HIV patients treated in South East Asia
Abstract
Aim: Immune restoration disease (IRD) associated with Mycobacterium tuberculosis parallels the reconstitution of a pathogen-specific Th1 response. However, it is not clear whether humoral responses to M. tuberculosis antigens also rise, or whether antibody levels predict IRD. Here, humoral immunity to M. tuberculosis antigens was investigated in four Asian cohorts. Methods: Plasma samples were obtained from longitudinal prospective studies of HIV patients beginning antiretroviral therapy (ART) in New Delhi (India), Kuala Lumpur (Malaysia), Jakarta (Indonesia) and Phnom Penh (Cambodia). IgG antibodies to purified protein derivative, lipoarabinomannan and 38-kDa antigens of M. tuberculosis were quantitated using in-house ELISAs. IRD was defined as exacerbated symptoms of tuberculosis in patients on anti-tuberculosis therapy or a novel presentation of tuberculosis on ART. Results: Pre-ART IgG levels to purified protein derivative, lipoarabinomannan and 38-kDa antigen were similar in the IRD and control groups from each site. Compared with non-IRD controls, a higher proportion of IRD patients had elevated IgG levels to lipoarabinomannan (defined as a greater than twofold increase) over 12 weeks of ART. However, this trend was not significant for the other antigens and longitudinal analyses did not reveal clear rises in antibody levels at the time of IRD. Conclusion: Levels of antibody to mycobacterial antigens do not predict IRD, but levels of antibody reactive with lipoarabinomannan rise during an IRD in some patients.
References
- 1 Lazarous DG, O’ Donnell AE. Pulmonary infections in the HIV-infected patient in the era of highly active antiretroviral therapy. An update. Curr. Infect. Dis. Rep.9(3),228–232 (2007).Crossref, Medline, Google Scholar
- 2 Blanc FX, Havlir DV, Onyebujoh PC, Thim S, Goldfeld AE, Delfraissy JF. Treatment strategies for HIV-infected patients with tuberculosis. Ongoing and planned clinical trials. J. Infect. Dis.196,46–51 (2007).Crossref, Medline, Google Scholar
- 3 Price P, Murdoch DM, Agarwal U, Lewin SR, Elliot JH, French MA. Immune restoration diseases reflect diverse immunopathological mechanisms. Clin. Microbiol. Rev.22,651–663 (2009).Crossref, Medline, Google Scholar
- 4 Meintjes GA, Lawn SD, Scano F et al. Tuberculosis immune reconstitution inflammatory syndrome. Case definitions for use in resource-limited settings. Lancet Infect. Dis.8(8),516–528 (2008).Crossref, Medline, Google Scholar
- 5 Bourgarit A, Carcelain G, Martinez V et al. Explosion of tuberculin-specific Th1-responses induces immune restoration syndrome in tuberculosis and HIV coinfected patients. AIDS20(2),F1–F7 (2006).Crossref, Medline, CAS, Google Scholar
- 6 French MA. Immune reconstitution inflammatory syndrome. A reappraisal. Clin. Infect. Dis.48,101–107 (2009).Crossref, Medline, Google Scholar
- 7 Tan DBA, Yong YK, Kamarulzaman A et al. Immunological profiles of immune restoration disease presenting as mycobacterial lymphadenitis and cryptococcal meningitis. HIV Med.9(5),307–316 (2008).Crossref, Medline, CAS, Google Scholar
- 8 Skolimowska K, Meintjes G, Wilkinson KA et al. Effect of steroids on T-cell expansions in HIV-tuberculosis immune reconstitution inflammatory syndrome. Presented at: 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Cape Town, South Africa 19–22 July 2009 (Abstract TUPEB146).Google Scholar
- 9 Stone SF, Lee S, Keane NM, Price P, French MA. Association of increased hepatitis C virus (HCV)-specific IgG and soluble CD26 dipeptidyl peptidase IV enzyme activity with hepatotoxicity after highly active antiretroviral therapy in human immunodeficiency virus-HCV-coinfected patients. J. Infect. Dis.186(10),1498–1502 (2002).Crossref, Medline, CAS, Google Scholar
- 10 Stone SF, Price P, Tay-Kearney ML, French MA. Cytomegalovirus (CMV) retinitis immune restoration disease occurs during highly active antiretroviral therapy-induced restoration of CMV-specific immune responses within a predominant Th2 cytokine environment. J. Infect. Dis.185(12),1813–1817 (2002).Crossref, Medline, CAS, Google Scholar
- 11 Yunihastuti E, Lee S, Gani RA, et al. Antibody and markers of T-cell activation illuminate the pathogenesis of HCV immune restoration disease in HIV/HCV co-infected patients commencing ART. Clin. Immunol.139,32–39 (2011).Crossref, Medline, CAS, Google Scholar
- 12 Simonney N, Dewulf G, Hermann JL et al. Anti-PGL-Tb1 responses as an indicator of the immune restoration syndrome in HIV-TB patients. Tuberculosis88(5),453–461 (2008).Crossref, Medline, CAS, Google Scholar
- 13 Chatterjee D, Hunter SW, McNeil M, Brennan PJ. Lipoarabinomannan. Multiglycosylated form of the mycobacterial mannosylphosphotidylinositols. J. Biol. Chem.267,6228–6233 (1992).Crossref, Medline, CAS, Google Scholar
- 14 Hunter SW, Gaylord H, Brennan PJ. Structure and antigenicity of the phosphorylated lipopolysaccharide antigens from the leprosy and tubercle bacilli. J. Biol. Chem.261,12345–12351 (1986).Crossref, Medline, CAS, Google Scholar
- 15 Chan J, Fan X, Hunter SW, Brennan PJ, Bloom BR. Lipoarabinomannan, a possible virulence factor involved in persistence of Mycobacterium tuberculosis within macrophages. Infect. Immun.59(5),1755–1761 (1991).Crossref, Medline, CAS, Google Scholar
- 16 Da Fonseca DPA J, Joosten D, van der Zee R et al. Identification of new cytotoxic T-Cell epitopes on the 38 kilodalton lipoglycoprotein of Mycobacterium tuberculosis by using lipopeptides. Infect. Immun.66(7),3190–3197 (1998).Crossref, Medline, CAS, Google Scholar
- 17 Abebe F, Holm-Hanset C, Wiker HG, Bjune G. Progress in serodiagnosis of Mycobacterium tuberculosis infection. Scand. J. Immunol.66,176–191 (2007).Crossref, Medline, CAS, Google Scholar
- 18 Boggian K, Fierz W, Vernazza PL. Infrequent detection of lipoarabinomannan in human immunodeficiency virus-associated mycobacterial disease. Swiss HIV cohort study. J. Clin. Microbiol.34(7),1854–1855 (1996).Crossref, Medline, CAS, Google Scholar
- 19 Perkins MD, Cunningham J. Facing the crisis. Improving the diagnosis of tuberculosis in the HIV era. J. Infect. Dis.196(1),15–27 (2007).Crossref, Medline, Google Scholar
- 20 French MA, Price P, Stone SF. Immune restoration disease after antiretroviral therapy. AIDS18(12),1615–1627 (2004).Crossref, Medline, CAS, Google Scholar
- 21 Beyene D, Franken Kl, Yamuah L et al. Serodiagnosis of tuberculous lymphadenitis using a combination of antigens. J. Infect. Dev. Ctries4(2),96–102 (2010).Crossref, Medline, CAS, Google Scholar
- 22 Mahon RN, Rojas RE, Fulton SA, Franko JL, Harding CV, Boom WH. Mycobacterium tuberculosis cell wall glycolipids directly inhibit CD4+ T-cell activation by interfering with proximal T-cell-receptor signaling. Infect. Immun.77(10),4574–4583 (2009).Crossref, Medline, CAS, Google Scholar
- 23 Sousa AO, Henry S, Maroja FM et al. IgG subclass distribution of antibody responses to protein and polysaccharide mycobacterial antigens in leprosy and tuberculosis patients. Clin. Exp. Immunol.111(1),49–55 (1998).Crossref, Google Scholar
- 24 Demkow U, Filewska M, Michalowska-Mitczuk D et al. Heterogeneity of antibody response to mycobacterial antigens in different clinical manifestations of pulmonary tuberculosis. J. Physiol. Pharmacol.58(5),117–127 (2007).Medline, Google Scholar
- 101 World Health Organization. Management of tuberculosis and HIV coinfection. Clinical protocol for the WHO European region (2008). www.euro.who.int/document/SHA/e90840_chapter_4.pdfGoogle Scholar
