Changes in Immune Activation During Pregnancy and the Postpartum Period in Treated HIV Infection.
3-dioxygenase-1
HIV
indoleamine 2
inflammation
kynurenine/tryptophan ratio
pregnancy
Journal
Open forum infectious diseases
ISSN: 2328-8957
Titre abrégé: Open Forum Infect Dis
Pays: United States
ID NLM: 101637045
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
15
02
2021
accepted:
12
05
2021
entrez:
23
6
2021
pubmed:
24
6
2021
medline:
24
6
2021
Statut:
epublish
Résumé
Pregnant women with HIV (PWWH) have high postpartum morbidity and mortality from infections like tuberculosis. Immunologic changes during pregnancy and postpartum periods may contribute to these risks, particularly the immunoregulatory kynurenine pathway of tryptophan catabolism, which contributes to both HIV and tuberculosis pathogenesis and increases in the early postpartum period. Women with HIV initiating antiretroviral therapy (ART) in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort who were pregnant at enrollment or became pregnant during observation were studied (n = 54). Plasma kynurenine/tryptophan (KT) ratio, soluble CD14 (sCD14), sCD163, sCD27, interferon-inducible protein 10 (IP-10), D-dimer, interleukin-6, and intestinal fatty-acid binding protein levels were assessed through the first year of ART and at 3-month intervals throughout pregnancy and 1 year postpartum. Biomarker changes were assessed with linear mixed models adjusted for ART duration. Hemoglobin concentration changes were used to estimate pregnancy-related changes in plasma volume. The median pre-ART CD4 count was 134. D-dimer increased through the third trimester before returning to baseline postpartum, while most other biomarkers declined significantly during pregnancy, beyond what would be expected from pregnancy-associated plasma volume expansion. IP-10 and sCD14 remained suppressed for at least 12 months postpartum. KT ratio was the only biomarker that increased above prepregnancy baseline postpartum (mean + 30%; Several immune activation markers decline during pregnancy and remain suppressed postpartum, but the kynurenine pathway of tryptophan catabolism increases above baseline for ≥9 months postpartum. The mechanisms underlying postpartum kynurenine pathway activity are incompletely understood but may contribute to increased tuberculosis risk in this setting.
Sections du résumé
BACKGROUND
BACKGROUND
Pregnant women with HIV (PWWH) have high postpartum morbidity and mortality from infections like tuberculosis. Immunologic changes during pregnancy and postpartum periods may contribute to these risks, particularly the immunoregulatory kynurenine pathway of tryptophan catabolism, which contributes to both HIV and tuberculosis pathogenesis and increases in the early postpartum period.
METHODS
METHODS
Women with HIV initiating antiretroviral therapy (ART) in the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort who were pregnant at enrollment or became pregnant during observation were studied (n = 54). Plasma kynurenine/tryptophan (KT) ratio, soluble CD14 (sCD14), sCD163, sCD27, interferon-inducible protein 10 (IP-10), D-dimer, interleukin-6, and intestinal fatty-acid binding protein levels were assessed through the first year of ART and at 3-month intervals throughout pregnancy and 1 year postpartum. Biomarker changes were assessed with linear mixed models adjusted for ART duration. Hemoglobin concentration changes were used to estimate pregnancy-related changes in plasma volume.
RESULTS
RESULTS
The median pre-ART CD4 count was 134. D-dimer increased through the third trimester before returning to baseline postpartum, while most other biomarkers declined significantly during pregnancy, beyond what would be expected from pregnancy-associated plasma volume expansion. IP-10 and sCD14 remained suppressed for at least 12 months postpartum. KT ratio was the only biomarker that increased above prepregnancy baseline postpartum (mean + 30%;
CONCLUSIONS
CONCLUSIONS
Several immune activation markers decline during pregnancy and remain suppressed postpartum, but the kynurenine pathway of tryptophan catabolism increases above baseline for ≥9 months postpartum. The mechanisms underlying postpartum kynurenine pathway activity are incompletely understood but may contribute to increased tuberculosis risk in this setting.
Identifiants
pubmed: 34159218
doi: 10.1093/ofid/ofab245
pii: ofab245
pmc: PMC8214017
doi:
Types de publication
Journal Article
Langues
eng
Pagination
ofab245Subventions
Organisme : NHLBI NIH HHS
ID : R38 HL143581
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH054907
Pays : United States
Organisme : NIAID NIH HHS
ID : K24 AI145806
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI078774
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI076174
Pays : United States
Organisme : NICHD NIH HHS
ID : R21 HD069194
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI027763
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI100765
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
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