Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patients
Abstract Background Little is known regarding the restoration of the specific immune response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) therapy introduction among TB-HIV patients. In this study, we examined the immune response of TB-HIV patients to Mycobacterium tubercu...
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| Format: | Article |
| Language: | English |
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BMC
2017-09-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | http://link.springer.com/article/10.1186/s12879-017-2700-6 |
| _version_ | 1818502373415321600 |
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| author | Tatiana Pereira da Silva Carmem Beatriz Wagner Giacoia-Gripp Carolina A. Schmaltz Flavia Marinho Sant’Anna Maria Helena Saad Juliana Arruda de Matos Julio Castro Alves de Lima e Silva Valeria Cavalcanti Rolla Mariza Gonçalves Morgado |
| author_facet | Tatiana Pereira da Silva Carmem Beatriz Wagner Giacoia-Gripp Carolina A. Schmaltz Flavia Marinho Sant’Anna Maria Helena Saad Juliana Arruda de Matos Julio Castro Alves de Lima e Silva Valeria Cavalcanti Rolla Mariza Gonçalves Morgado |
| author_sort | Tatiana Pereira da Silva |
| collection | DOAJ |
| description | Abstract Background Little is known regarding the restoration of the specific immune response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) therapy introduction among TB-HIV patients. In this study, we examined the immune response of TB-HIV patients to Mycobacterium tuberculosis (Mtb) antigens to evaluate the response dynamics to different antigens over time. Moreover, we also evaluated the influence of two different doses of efavirenz and the factors associated with immune reconstitution. Methods This is a longitudinal study nested in a clinical trial, where cART was initiated during the baseline visit (D0), which occurred 30 ± 10 days after the introduction of anti-TB therapy. Follow-up visits were performed at 30, 60, 90 and 180 days after cART initiation. The production of IFN-γ upon in vitro stimulation with Mtb antigens purified protein derivative (PPD), ESAT-6 and 38 kDa/CFP-10 using ELISpot was examined at baseline and follow-up visits. Results Sixty-one patients, all ART-naïve, were selected and included in the immune reconstitution analysis; seven (11.5%) developed Immune Reconstitution Inflammatory Syndrome (IRIS). The Mtb specific immune response was higher for the PPD antigen followed by 38 kDa/CFP-10 and increased in the first 60 days after cART initiation. In multivariate analysis, the variables independently associated with increased IFN-γ production in response to PPD antigen were CD4+ T cell counts <200 cells/mm3 at baseline, age, site of tuberculosis, 800 mg efavirenz dose and follow-up CD4+ T cell counts. Moreover, the factors associated with the production of IFN-γ in response to 38 kDa/CFP-10 were detectable HIV viral load (VL) and CD4+ T cell counts at follow-up visits of ≥200 cells/mm3. Conclusions These findings highlight the differences in immune response according to the specificity of the Mtb antigen, which contributes to a better understanding of TB-HIV immunopathogenesis. IFN-γ production elicited by PPD and 38 kDa/CFP-10 antigens have a greater magnitude compared to ESAT-6 and are associated with different factors. The low response to ESAT-6, even during immune restoration, suggests that this antigen is not adequate to assess the immune response of immunosuppressed TB-HIV patients. |
| first_indexed | 2024-12-10T21:09:23Z |
| format | Article |
| id | doaj.art-c5628fbd36ce4a2a8bd885dd9f93db18 |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-10T21:09:23Z |
| publishDate | 2017-09-01 |
| publisher | BMC |
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| series | BMC Infectious Diseases |
| spelling | doaj.art-c5628fbd36ce4a2a8bd885dd9f93db182022-12-22T01:33:32ZengBMCBMC Infectious Diseases1471-23342017-09-0117111010.1186/s12879-017-2700-6Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patientsTatiana Pereira da Silva0Carmem Beatriz Wagner Giacoia-Gripp1Carolina A. Schmaltz2Flavia Marinho Sant’Anna3Maria Helena Saad4Juliana Arruda de Matos5Julio Castro Alves de Lima e Silva6Valeria Cavalcanti Rolla7Mariza Gonçalves Morgado8Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute, Fundação Oswaldo Cruz (FIOCRUZ)Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute, Fundação Oswaldo Cruz (FIOCRUZ)Clinical Research Laboratory on Mycobacteria - National Institute of Infectious Diseases Evandro Chagas (FIOCRUZ)Clinical Research Laboratory on Mycobacteria - National Institute of Infectious Diseases Evandro Chagas (FIOCRUZ)Laboratory of Cellular Microbiology, Oswaldo Cruz Institute, Fundação Oswaldo Cruz (FIOCRUZ)Clinical Research Laboratory on Health Surveillance and Immunization - National Institute of Infectious Diseases Evandro Chagas (FIOCRUZ)Platform for Clinical Research - National Institute of Infectious Diseases Evandro Chagas (FIOCRUZ)Clinical Research Laboratory on Mycobacteria - National Institute of Infectious Diseases Evandro Chagas (FIOCRUZ)Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute, Fundação Oswaldo Cruz (FIOCRUZ)Abstract Background Little is known regarding the restoration of the specific immune response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) therapy introduction among TB-HIV patients. In this study, we examined the immune response of TB-HIV patients to Mycobacterium tuberculosis (Mtb) antigens to evaluate the response dynamics to different antigens over time. Moreover, we also evaluated the influence of two different doses of efavirenz and the factors associated with immune reconstitution. Methods This is a longitudinal study nested in a clinical trial, where cART was initiated during the baseline visit (D0), which occurred 30 ± 10 days after the introduction of anti-TB therapy. Follow-up visits were performed at 30, 60, 90 and 180 days after cART initiation. The production of IFN-γ upon in vitro stimulation with Mtb antigens purified protein derivative (PPD), ESAT-6 and 38 kDa/CFP-10 using ELISpot was examined at baseline and follow-up visits. Results Sixty-one patients, all ART-naïve, were selected and included in the immune reconstitution analysis; seven (11.5%) developed Immune Reconstitution Inflammatory Syndrome (IRIS). The Mtb specific immune response was higher for the PPD antigen followed by 38 kDa/CFP-10 and increased in the first 60 days after cART initiation. In multivariate analysis, the variables independently associated with increased IFN-γ production in response to PPD antigen were CD4+ T cell counts <200 cells/mm3 at baseline, age, site of tuberculosis, 800 mg efavirenz dose and follow-up CD4+ T cell counts. Moreover, the factors associated with the production of IFN-γ in response to 38 kDa/CFP-10 were detectable HIV viral load (VL) and CD4+ T cell counts at follow-up visits of ≥200 cells/mm3. Conclusions These findings highlight the differences in immune response according to the specificity of the Mtb antigen, which contributes to a better understanding of TB-HIV immunopathogenesis. IFN-γ production elicited by PPD and 38 kDa/CFP-10 antigens have a greater magnitude compared to ESAT-6 and are associated with different factors. The low response to ESAT-6, even during immune restoration, suggests that this antigen is not adequate to assess the immune response of immunosuppressed TB-HIV patients.http://link.springer.com/article/10.1186/s12879-017-2700-6TuberculosisAIDSImmune responseELISpotIRIS |
| spellingShingle | Tatiana Pereira da Silva Carmem Beatriz Wagner Giacoia-Gripp Carolina A. Schmaltz Flavia Marinho Sant’Anna Maria Helena Saad Juliana Arruda de Matos Julio Castro Alves de Lima e Silva Valeria Cavalcanti Rolla Mariza Gonçalves Morgado Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patients BMC Infectious Diseases Tuberculosis AIDS Immune response ELISpot IRIS |
| title | Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patients |
| title_full | Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patients |
| title_fullStr | Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patients |
| title_full_unstemmed | Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patients |
| title_short | Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patients |
| title_sort | risk factors for increased immune reconstitution in response to mycobacterium tuberculosis antigens in tuberculosis hiv infected antiretroviral naive patients |
| topic | Tuberculosis AIDS Immune response ELISpot IRIS |
| url | http://link.springer.com/article/10.1186/s12879-017-2700-6 |
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