A Mycobacterium tuberculosis Specific IgG3 Signature of Recurrent Tuberculosis
South Africa has the highest prevalence of HIV and tuberculosis (TB) co-infection globally. Recurrent TB, caused by relapse or reinfection, makes up the majority of TB cases in South Africa, and HIV infected individuals have a greater likelihood of developing recurrent TB. Given that TB remains a le...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.729186/full |
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| author | Stephanie Fischinger Stephanie Fischinger Deniz Cizmeci Deniz Cizmeci Sally Shin Leela Davies Patricia S. Grace Aida Sivro Aida Sivro Nonhlanhla Yende-Zuma Nonhlanhla Yende-Zuma Hendrik Streeck Sarah M. Fortune Sarah M. Fortune Douglas A. Lauffenburger Kogieleum Naidoo Kogieleum Naidoo Galit Alter |
| author_facet | Stephanie Fischinger Stephanie Fischinger Deniz Cizmeci Deniz Cizmeci Sally Shin Leela Davies Patricia S. Grace Aida Sivro Aida Sivro Nonhlanhla Yende-Zuma Nonhlanhla Yende-Zuma Hendrik Streeck Sarah M. Fortune Sarah M. Fortune Douglas A. Lauffenburger Kogieleum Naidoo Kogieleum Naidoo Galit Alter |
| author_sort | Stephanie Fischinger |
| collection | DOAJ |
| description | South Africa has the highest prevalence of HIV and tuberculosis (TB) co-infection globally. Recurrent TB, caused by relapse or reinfection, makes up the majority of TB cases in South Africa, and HIV infected individuals have a greater likelihood of developing recurrent TB. Given that TB remains a leading cause of death for HIV infected individuals, and correlates of TB recurrence protection/risk have yet to be defined, here we sought to understand the antibody associated mechanisms of recurrent TB by investigating the humoral response in a longitudinal cohort of HIV co-infected individuals previously treated for TB with and without recurrent disease during follow-up, in order to identify antibody correlates of protection between individuals who do not have recurrent TB and individuals who do. We used a high-throughput, “systems serology” approach to profile biophysical and functional characteristics of antibodies targeting antigens from Mycobacterium tuberculosis (Mtb). Differences in antibody profiles were noted between individuals with and without recurrent TB, albeit these differences were largely observed close to the time of re-diagnosis. Individuals with recurrent TB had decreased Mtb-antigen specific IgG3 titers, but not other IgG subclasses or IgA, compared to control individuals. These data point to a potential role for Mtb-specific IgG3 responses as biomarkers or direct mediators of protective immunity against Mtb recurrence. |
| first_indexed | 2024-12-19T21:08:01Z |
| format | Article |
| id | doaj.art-8606591427d449929f59cab8b65734f8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T21:08:01Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-8606591427d449929f59cab8b65734f82022-12-21T20:05:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.729186729186A Mycobacterium tuberculosis Specific IgG3 Signature of Recurrent TuberculosisStephanie Fischinger0Stephanie Fischinger1Deniz Cizmeci2Deniz Cizmeci3Sally Shin4Leela Davies5Patricia S. Grace6Aida Sivro7Aida Sivro8Nonhlanhla Yende-Zuma9Nonhlanhla Yende-Zuma10Hendrik Streeck11Sarah M. Fortune12Sarah M. Fortune13Douglas A. Lauffenburger14Kogieleum Naidoo15Kogieleum Naidoo16Galit Alter17Ragon Institute of MGH, MIT and Harvard, Boston, MA, United StatesUniversity of Duisburg-Essen, Essen, GermanyRagon Institute of MGH, MIT and Harvard, Boston, MA, United StatesDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United StatesRagon Institute of MGH, MIT and Harvard, Boston, MA, United StatesRagon Institute of MGH, MIT and Harvard, Boston, MA, United StatesRagon Institute of MGH, MIT and Harvard, Boston, MA, United StatesCentre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South AfricaDepartment of Medical Microbiology, University of KwaZulu-Natal, Durban, South AfricaCentre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South AfricaMedical Research Council - Centre for the AIDS Programme of Research in South Africa (MRC-CAPRISA) HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South AfricaDepartment of Virology, University of Bonn, Bonn, GermanyRagon Institute of MGH, MIT and Harvard, Boston, MA, United StatesDepartment of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, United StatesDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United StatesCentre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South AfricaMedical Research Council - Centre for the AIDS Programme of Research in South Africa (MRC-CAPRISA) HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South AfricaRagon Institute of MGH, MIT and Harvard, Boston, MA, United StatesSouth Africa has the highest prevalence of HIV and tuberculosis (TB) co-infection globally. Recurrent TB, caused by relapse or reinfection, makes up the majority of TB cases in South Africa, and HIV infected individuals have a greater likelihood of developing recurrent TB. Given that TB remains a leading cause of death for HIV infected individuals, and correlates of TB recurrence protection/risk have yet to be defined, here we sought to understand the antibody associated mechanisms of recurrent TB by investigating the humoral response in a longitudinal cohort of HIV co-infected individuals previously treated for TB with and without recurrent disease during follow-up, in order to identify antibody correlates of protection between individuals who do not have recurrent TB and individuals who do. We used a high-throughput, “systems serology” approach to profile biophysical and functional characteristics of antibodies targeting antigens from Mycobacterium tuberculosis (Mtb). Differences in antibody profiles were noted between individuals with and without recurrent TB, albeit these differences were largely observed close to the time of re-diagnosis. Individuals with recurrent TB had decreased Mtb-antigen specific IgG3 titers, but not other IgG subclasses or IgA, compared to control individuals. These data point to a potential role for Mtb-specific IgG3 responses as biomarkers or direct mediators of protective immunity against Mtb recurrence.https://www.frontiersin.org/articles/10.3389/fimmu.2021.729186/fullrecurrent tuberculosisantibodiesIgG3Mycobacterium tuberculosisrecurrence |
| spellingShingle | Stephanie Fischinger Stephanie Fischinger Deniz Cizmeci Deniz Cizmeci Sally Shin Leela Davies Patricia S. Grace Aida Sivro Aida Sivro Nonhlanhla Yende-Zuma Nonhlanhla Yende-Zuma Hendrik Streeck Sarah M. Fortune Sarah M. Fortune Douglas A. Lauffenburger Kogieleum Naidoo Kogieleum Naidoo Galit Alter A Mycobacterium tuberculosis Specific IgG3 Signature of Recurrent Tuberculosis Frontiers in Immunology recurrent tuberculosis antibodies IgG3 Mycobacterium tuberculosis recurrence |
| title | A Mycobacterium tuberculosis Specific IgG3 Signature of Recurrent Tuberculosis |
| title_full | A Mycobacterium tuberculosis Specific IgG3 Signature of Recurrent Tuberculosis |
| title_fullStr | A Mycobacterium tuberculosis Specific IgG3 Signature of Recurrent Tuberculosis |
| title_full_unstemmed | A Mycobacterium tuberculosis Specific IgG3 Signature of Recurrent Tuberculosis |
| title_short | A Mycobacterium tuberculosis Specific IgG3 Signature of Recurrent Tuberculosis |
| title_sort | mycobacterium tuberculosis specific igg3 signature of recurrent tuberculosis |
| topic | recurrent tuberculosis antibodies IgG3 Mycobacterium tuberculosis recurrence |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.729186/full |
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