Biofilm-derived oxylipin 10-HOME–mediated immune response in women with breast implants
Imran Khan, … , Marshall E. Kadin, Mithun Sinha
Imran Khan, … , Marshall E. Kadin, Mithun Sinha
Published November 30, 2023
Citation Information: J Clin Invest. 2024;134(3):e165644. https://doi.org/10.1172/JCI165644.
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Research Article Immunology Inflammation

Biofilm-derived oxylipin 10-HOME–mediated immune response in women with breast implants

Abstract

This study investigates a mechanistic link of bacterial biofilm–mediated host-pathogen interaction leading to immunological complications associated with breast implant illness (BII). Over 10 million women worldwide have breast implants. In recent years, women have described a constellation of immunological symptoms believed to be related to their breast implants. We report that periprosthetic breast tissue of participants with symptoms associated with BII had increased abundance of biofilm and biofilm-derived oxylipin 10-HOME compared with participants with implants who are without symptoms (non-BII) and participants without implants. S. epidermidis biofilm was observed to be higher in the BII group compared with the non-BII group and the normal tissue group. Oxylipin 10-HOME was found to be immunogenically capable of polarizing naive CD4+ T cells with a resulting Th1 subtype in vitro and in vivo. Consistently, an abundance of CD4+Th1 subtype was observed in the periprosthetic breast tissue and blood of people in the BII group. Mice injected with 10-HOME also had increased Th1 subtype in their blood, akin to patients with BII, and demonstrated fatigue-like symptoms. The identification of an oxylipin-mediated mechanism of immune activation induced by local bacterial biofilm provides insight into the possible pathogenesis of the implant-associated immune symptoms of BII.

Authors

Imran Khan, Robert E. Minto, Christine Kelley-Patteson, Kanhaiya Singh, Lava Timsina, Lily J. Suh, Ethan Rinne, Bruce W. Van Natta, Colby R. Neumann, Ganesh Mohan, Mary Lester, R. Jason VonDerHaar, Rana German, Natascia Marino, Aladdin H. Hassanein, Gayle M. Gordillo, Mark H. Kaplan, Chandan K. Sen, Marshall E. Kadin, Mithun Sinha

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Figure 2

Increased abundance of biofilm-derived 10-HOME in participants with BII.

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Increased abundance of biofilm-derived 10-HOME in participants with BII....
(A) Schematic of formation of 10-HOME from oleic acid. (B–D). Increased abundance of 10-HOME in implant-associated tissue of participants with BII. (B) Chromatograms of 10-HOME from non-BII and BII tissues using LC-MS/MS targeted analyses. (C) Data presented as mean ± SEM, n = 6 (non-BII), n = 17 (BII), t test was used to determine BII versus non-BII (P < 0.0001). (D) Receiver operating characteristic (ROC) curve analysis to determine specificity and sensitivity of 10-HOME detection. (E) Increased abundance of bacteria associated with 10-HOME detected from the implant-associated tissue of participants with BII. (F) Increased abundance of Staphylococcus epidermidis associated with 10-HOME detected from the implant-associated tissue of participants with BII. (G) Synthesis of 10-HOME by S. epidermidis in vitro upon using oleic acid as carbon source. Gas chromatography-mass spectrometry analyses for detection of 10-HOME derivatized both as trimethylsilyl ethers and methyl estersoleic acid standard, 10-HOME standard, S. epidermidis with glucose as carbon source, S. epidermidis with oleic acid as carbon source, quantification of 10-HOME abundance. n = 4. t test was used to determine glucose versus oleic acid (P < 0.0001).