Systemic Inflammation in Pregnant Women With Latent Tuberculosis Infection

Abstract

BackgroundRecent studies in adults have characterized differences in systemic inflammation between adults with and without latent tuberculosis infection (LTBI+ vs. LTBI−). Potential differences in systemic inflammation by LTBI status has not been assess in pregnant women.MethodsWe conducted a cohort study of 155 LTBI+ and 65 LTBI− pregnant women, stratified by HIV status, attending an antenatal clinic in Pune, India. LTBI status was assessed by interferon gamma release assay. Plasma was used to measure systemic inflammation markers using immunoassays: IFNβ, CRP, AGP, I-FABP, IFNγ, IL-1β, soluble CD14 (sCD14), sCD163, TNF, IL-6, IL-17a and IL-13. Linear regression models were fit to test the association of LTBI status with each inflammation marker. We also conducted an exploratory analysis using logistic regression to test the association of inflammatory markers with TB progression.ResultsStudy population was a median age of 23 (Interquartile range: 21–27), 28% undernourished (mid-upper arm circumference (MUAC) <23 cm), 12% were vegetarian, 10% with gestational diabetes and 32% with HIV. In multivariable models, LTBI+ women had significantly lower levels of third trimester AGP, IL1β, sCD163, IL-6 and IL-17a. Interestingly, in exploratory analysis, LTBI+ TB progressors had significantly higher levels of IL1β, IL-6 and IL-13 in multivariable models compared to LTBI+ non-progressors.ConclusionsOur data shows a distinct systemic immune profile in LTBI+ pregnant women compared to LTBI− women. Data from our exploratory analysis suggest that LTBI+ TB progressors do not have this immune profile, suggesting negative association of this profile with TB progression. If other studies confirm these differences by LTBI status and show a causal relationship with TB progression, this immune profile could identify subsets of LTBI+ pregnant women at high risk for TB progression and who can be targeted for preventative therapy.

Longitudinal Variations of M. tuberculosis-Induced IFN-γ Responses in HIV-Negative Pregnant Women Exposed to Tuberculosis

“…While our study seems to confirm this global decline in the IFN-g responses observed from other longitudinal studies in pregnant women (7,20), the additional parallel comparison of the IFN-g response with that of control non-pregnant women of similar age in our study showed that this IFN-g response is strongly requested following an exposition to M. tuberculosis in pregnant women. Similar immune responses with a strong IFN-g production were observed among LTBI+ pregnant women in India after the comparison with LTBI-pregnant women (10). This strong activation of IFN-g following an exposition to M. tuberculosis and observations made on the antiviral immune response in pregnant woman seems to confirm the fact that pregnancy is not a period of immunosuppression notably for Th1 but a temporary attenuation in immune responses characterized by a strengthening of innate immune barriers and a concomitant reduction in pro-inflammatory immunity that is resumed when exposed to infections (21,22).…”

“…Second, we have not investigated other TB-specific cytokines. There are changes among other cytokines that are specific to pregnancy ( 10 ). The next steps for this study would be to better understand the impact of these variations by assessing other cytokines and biomarkers of LTBI and/or progression to active TB.…”

“…Interferon-gamma release assays (IGRAs) are immunoassays based on the measure of the production of IFN-γ produced after T cell ex vivo stimulation by M. tuberculosis -specific antigens also used to assess for a previous exposure or infection to M. tuberculosis . Recent studies on the IFN-γ response changes in M. tuberculosis latently infected pregnant women (pLTBI+) using IGRAs suggested a slight increase of the Th1 pro-inflammatory response to a concentration sufficient to contain the latent infection in these pregnant women ( 7 – 9 and 10 ). However, few data are available on this IFN-γ immune response status in pregnant women with active TB disease.…”

Association of Maternal Inflammation During Pregnancy With Birth Outcomes and Infant Growth Among Women With or Without HIV in India

“…We conducted a longitudinal cohort study of pregnant women (PRACHITi [Pregnancy Associated Changes in Tuberculosis Immunology] study) in Pune, India, from June 27, 2016, to December 9, 2019. 7 We enrolled adult pregnant women aged 18 to 40 years and between 13 and 34 weeks of gestation (confirmed by early pregnancy ultrasonography) who were receiving antenatal care at Byramjee Jeejeebhoy Government Medical College, a tertiary care hospital that serves primarily low-income populations and is a referral center for HIV care. The study excluded pregnant women with active tuberculosis or severe anemia at entry, as well as women who were taking antibiotics for more than 14 days, had a history of an autoimmune or immunosuppressive disease, or were taking immunosuppressive medication.…”

Tuberculosis infection and stillbirth in Ethiopia—A prospective cohort study

“…Interestingly, elevated levels of biomarkers of systemic inflammation have also been reported in persons with LTBI [ 42 – 45 ], and a recent study revealed differences in peripheral blood cytokine profiles among Indian pregnant women with LTBI compared to TB-uninfected women [ 46 ]. Furthermore, recent observational studies have suggested associations between LTBI and myocardial infarction and atherosclerosis [ 47 , 48 ], which has been suggested to be linked to chronic low-grade inflammation.…”