4.7 Article

Higher mucosal antibody concentrations in women with genital tract inflammation

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SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-021-02954-0

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资金

  1. USAID [FHI360]
  2. CONRAD
  3. South African Department of Science and Technology (DST)
  4. USAID through CONRAD [GPO-A-00-08-00005-00]
  5. PEPFAR, DST through the Technology Innovation Agency
  6. MACAIDS Fund through the Tides Foundation [TFR11-01545]
  7. Department of Science and Innovation (DSI)-National Research Foundation (NRF) Centre of Excellence in HIV Prevention [96354]
  8. South African Medical Research Council (SAMRC) Special Initiative [96151]
  9. S&F Scarce Skills Postdoctoral Fellowships [132714]
  10. NRF Research Career Advancement Fellowship award
  11. SANTHE Path to Independence award
  12. African Academy of Sciences
  13. Royal Society
  14. EDCTP Career Development Fellowship [TMA2016CDF-1582]
  15. NIH [5R01AI111936]
  16. SAMRC Self-Initiated Grant
  17. NRF of South Africa Thuthuka [TTK160517165310]
  18. NRF Research Career Advancement Fellowship [RCA13101656388]
  19. Polio Research Foundation of South Africa [PRF 17/02]
  20. EDCTP Senior Fellowship [TMA2017SF-1960]

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This study investigated the impact of genital inflammation on antibody isotypes and IgG subclasses in the female genital tract before HIV infection. It found that women with genital inflammation had significantly higher levels of IgM, IgG1, IgG3, IgG4 compared to those without. Pro-inflammatory cytokines were significantly correlated with higher levels of mucosal antibodies, suggesting a potential link between local inflammation and mucosal antibody profiles.
Inflammatory cytokines augment humoral responses by stimulating antibody production and inducing class-switching. In women, genital inflammation (GI) significantly modifies HIV risk. However, the impact of GI on mucosal antibodies remains undefined. We investigated the impact of GI, pre-HIV infection, on antibody isotypes and IgG subclasses in the female genital tract. Immunoglobulin (Ig) isotypes, IgG subclasses and 48 cytokines were measured prior to HIV infection in cervicovaginal lavages (CVL) from 66 HIV seroconverters (cases) and 66 matched HIV-uninfected women (controls) enrolled in the CAPRISA 004 and 008 1% tenofovir gel trials. Pre-HIV infection, cases had significantly higher genital IgM (4.13; IQR, 4.04-4.19) compared to controls (4.06; IQR, 3.90-4.20; p = 0.042). More than one-quarter of cases (27%) had GI compared to just over one-tenth (12%) in controls. Significantly higher IgG1, IgG3, IgG4 and IgM (all p < 0.05) were found in women stratified for GI compared to women without. Adjusted linear mixed models showed several pro-inflammatory, chemotactic, growth factors, and adaptive cytokines significantly correlated with higher titers of IgM, IgA and IgG subclasses (p < 0.05). The strong and significant positive correlations between mucosal antibodies and markers of GI suggest that GI may impact mucosal antibody profiles. These findings require further investigation to establish a plausible biological link between the local inflammatory milieu and its consequence on these genital antibodies.

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