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A Mycobacterium tuberculosis Specific IgG3 Signature of Recurrent Tuberculosis

  • Fischinger, Stephanie1, 2
  • Cizmeci, Deniz1, 3
  • Shin, Sally1
  • Davies, Leela1
  • Grace, Patricia S.1
  • Sivro, Aida4, 5
  • Yende-Zuma, Nonhlanhla4, 6
  • Streeck, Hendrik7
  • Fortune, Sarah M.1, 8
  • Lauffenburger, Douglas A.3
  • Naidoo, Kogieleum4, 6
  • Alter, Galit1
  • 1 Ragon Institute of MGH, MIT and Harvard, Boston, MA , (United States)
  • 2 University of Duisburg-Essen, Essen , (Germany)
  • 3 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA , (United States)
  • 4 Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban , (South Africa)
  • 5 Department of Medical Microbiology, University of KwaZulu-Natal, Durban , (South Africa)
  • 6 Medical 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 Africa)
  • 7 Department of Virology, University of Bonn, Bonn , (Germany)
  • 8 Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA , (United States)
Published Article
Frontiers in Immunology
Frontiers Media SA
Publication Date
Sep 22, 2021
DOI: 10.3389/fimmu.2021.729186
PMCID: PMC8493041
PubMed Central
  • Immunology
  • Original Research


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.

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