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The immune response to sub-clinical mastitis is impaired in HIV-infected women

The immune response to sub-clinical mastitis is impaired in HIV-infected women
The immune response to sub-clinical mastitis is impaired in HIV-infected women

Background: Subclinical mastitis (SCM) is relatively common in lactating women and may be associated with HIV shedding in breast milk. The potential association between HIV infection and breast milk immunologic factors and immune response to SCM needs to be addressed. Methods: In this cross-sectional study, SCM (Na/K ratio > 1) was tested in 165 mature breast milk samples collected from 40 HIV-infected women who didn't transmit HIV to their child by breastfeeding and 43 HIV-uninfected women enrolled in an interventional cohort in South-Africa (Vertical Transmission Study). The level of 33 immune markers related to Th1/Th2 related response, inflammation and bacterial exposure were compared in ART-naive HIV-infected versus HIV-uninfected women. The associations between HIV infection and SCM on the concentration of immune factors were tested separately by Wilcoxon rank-sum test and corrected for false discovery rate. To control for potential confounder effects and take into account the clustering of breast milk samples from a single woman, multivariate mixed linear models adjusted on child age at the time of sampling were performed for each immune factor. Results: Subclinical mastitis was detected in 15 (37.5%) HIV-infected women and 10 (23.3%) HIV-uninfected women. In the absence of SCM, the breast milk levels of IP-10 and MIG were higher and IL1-RA lower in HIV-infected women than in HIV-uninfected women (respectively p < 0.001, p = 0.001, p = 0.045). In HIV-uninfected women, SCM was characterized by a robust immune response with higher concentrations of a broad panel of Th1 and inflammatory related immune markers than in samples without SCM. By contrast, in HIV-infected women a limited number of immune markers were increased and lower increases were observed in samples with SCM than without SCM. Conclusion: HIV infection in ART-naïve women was associated with elevated breast milk levels of IP-10 and MIG, which areTh1-related cytokines induced by IFN-γ. During SCM, a lower and narrower immune response was observed in HIV-infected than HIV-uninfected women, suggesting that HIV infection affects the capacity of the mammary gland to respond to SCM.

Breast milk, Cytokines, HIV, Subclinical mastitis
1479-5876
Schaub, Roxane
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Badiou, Stéphanie
e79a2c63-eb42-4536-8e96-4347e25eeebe
Viljoen, Johannes
a8699901-f83e-40c7-bc1b-460c9364e0f1
Dujols, Pierre
11b26893-d324-451b-9bd0-a7f311dcaf85
Bolloré, Karine
dd00e36b-fd11-4587-9185-245b9c3ac559
Van De Perre, Philippe
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Newell, Marie Louise
c6ff99dd-c23b-4fef-a846-a221fe2522b3
Bland, Ruth
8b24b75b-b7a3-4a7a-b79a-1d32ecc88667
Nagot, Nicolas
90e1e7dc-7b4f-4d92-b585-93a6f05e89ae
Tuaillon, Edouard
e1ffed65-ec67-4957-9c9b-1c262b93a39d
Schaub, Roxane
a9656033-92bf-4d59-9a22-c4de14020458
Badiou, Stéphanie
e79a2c63-eb42-4536-8e96-4347e25eeebe
Viljoen, Johannes
a8699901-f83e-40c7-bc1b-460c9364e0f1
Dujols, Pierre
11b26893-d324-451b-9bd0-a7f311dcaf85
Bolloré, Karine
dd00e36b-fd11-4587-9185-245b9c3ac559
Van De Perre, Philippe
602f078a-b13d-4d40-b191-304c547d7148
Newell, Marie Louise
c6ff99dd-c23b-4fef-a846-a221fe2522b3
Bland, Ruth
8b24b75b-b7a3-4a7a-b79a-1d32ecc88667
Nagot, Nicolas
90e1e7dc-7b4f-4d92-b585-93a6f05e89ae
Tuaillon, Edouard
e1ffed65-ec67-4957-9c9b-1c262b93a39d

Schaub, Roxane, Badiou, Stéphanie, Viljoen, Johannes, Dujols, Pierre, Bolloré, Karine, Van De Perre, Philippe, Newell, Marie Louise, Bland, Ruth, Nagot, Nicolas and Tuaillon, Edouard (2018) The immune response to sub-clinical mastitis is impaired in HIV-infected women. Journal of Translational Medicine, 16 (1), [296]. (doi:10.1186/s12967-018-1667-4).

Record type: Article

Abstract

Background: Subclinical mastitis (SCM) is relatively common in lactating women and may be associated with HIV shedding in breast milk. The potential association between HIV infection and breast milk immunologic factors and immune response to SCM needs to be addressed. Methods: In this cross-sectional study, SCM (Na/K ratio > 1) was tested in 165 mature breast milk samples collected from 40 HIV-infected women who didn't transmit HIV to their child by breastfeeding and 43 HIV-uninfected women enrolled in an interventional cohort in South-Africa (Vertical Transmission Study). The level of 33 immune markers related to Th1/Th2 related response, inflammation and bacterial exposure were compared in ART-naive HIV-infected versus HIV-uninfected women. The associations between HIV infection and SCM on the concentration of immune factors were tested separately by Wilcoxon rank-sum test and corrected for false discovery rate. To control for potential confounder effects and take into account the clustering of breast milk samples from a single woman, multivariate mixed linear models adjusted on child age at the time of sampling were performed for each immune factor. Results: Subclinical mastitis was detected in 15 (37.5%) HIV-infected women and 10 (23.3%) HIV-uninfected women. In the absence of SCM, the breast milk levels of IP-10 and MIG were higher and IL1-RA lower in HIV-infected women than in HIV-uninfected women (respectively p < 0.001, p = 0.001, p = 0.045). In HIV-uninfected women, SCM was characterized by a robust immune response with higher concentrations of a broad panel of Th1 and inflammatory related immune markers than in samples without SCM. By contrast, in HIV-infected women a limited number of immune markers were increased and lower increases were observed in samples with SCM than without SCM. Conclusion: HIV infection in ART-naïve women was associated with elevated breast milk levels of IP-10 and MIG, which areTh1-related cytokines induced by IFN-γ. During SCM, a lower and narrower immune response was observed in HIV-infected than HIV-uninfected women, suggesting that HIV infection affects the capacity of the mammary gland to respond to SCM.

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Accepted/In Press date: 17 October 2018
e-pub ahead of print date: 25 October 2018
Published date: 25 October 2018
Keywords: Breast milk, Cytokines, HIV, Subclinical mastitis

Identifiers

Local EPrints ID: 425976
URI: http://eprints.soton.ac.uk/id/eprint/425976
ISSN: 1479-5876
PURE UUID: 6edd173f-10b7-4f0f-baea-708ff7364d68
ORCID for Marie Louise Newell: ORCID iD orcid.org/0000-0002-1074-7699

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Date deposited: 08 Nov 2018 17:30
Last modified: 06 Jun 2024 01:52

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Contributors

Author: Roxane Schaub
Author: Stéphanie Badiou
Author: Johannes Viljoen
Author: Pierre Dujols
Author: Karine Bolloré
Author: Philippe Van De Perre
Author: Ruth Bland
Author: Nicolas Nagot
Author: Edouard Tuaillon

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