Browsing by Author "Lester, Mary"

Now showing 1 - 6 of 6
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    Biofilm Derived Oxylipin Mediated Autoimmune Response in Breast Implant Subjects
    (medRxiv, 2020-11-20) Khan, Imran; Minto, Robert E.; Kelley-Patteson, Christine; Natta, Bruce W. Van; Neumann, Colby R.; Suh, Lily J.; Singh, Kanhaiya; Lester, Mary; VonDerHaar, R. Jason; Gordillo, Gayle M.; Hassanein, Aladdin H.; Sen, Chandan K.; Kadin, Marshall E.; Sinha, Mithun; Chemistry and Chemical Biology, School of Science
    Over 10 million women worldwide have breast implants for breast cancer/prophylactic reconstruction or cosmetic augmentation. In recent years, a number of patients have described a constellation of symptoms that are believed to be related to their breast implants. This constellation of symptoms has been named Breast Implant Illness (BII). The symptoms described include chronic fatigue, joint pain, muscle pain and a host of other manifestations often associated with autoimmune illnesses. In this work, we report that bacterial biofilm is associated with BII. We postulate that the pathogenesis of BII is mediated via a host-pathogen interaction whereby the biofilm bacteria Staphylococcus epidermidis interacts with breast lipids to form the oxylipin 10-HOME. The oxylipin 10-HOME was found to activate CD4+ T cells to Th1 subtype. An increased abundance of CD4+Th1 was observed in the breast tissue of BII subjects. The identification of a mechanism of immune activation associated with BII via a biofilm enabled pathway provides insight into the pathogenesis for implant-associated autoimmune symptoms.
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    Biofilm-derived oxylipin 10-HOME–mediated immune response in women with breast implants
    (ASCI, 2024-02) Khan, Imran; Minto, Robert E.; Kelley-Patteson, Christine; Singh, Kanhaiya; Timsina, Lava; Suh, Lily J.; Rinne, Ethan; Van Natta, Bruce W.; Neumann, Colby R.; Mohan, Ganesh; Lester, Mary; VonDerHaar, R. Jason; German, Rana; Marino, Natascia; Hassanein, Aladdin H.; Gordillo, Gayle M.; Kaplan, Mark H.; Sen, Chandan K.; Kadin, Marshall E.; Sinha, Mithun; Chemistry, School of Science
    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.
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    Biofilm-derived oxylipin 10-HOME–mediated immune response in women with breast implants
    (The American Society for Clinical Investigation, 2023-11-30) Khan, Imran; Minto, Robert E.; Kelley-Patteson, Christine; Singh, Kanhaiya; Timsina, Lava; Suh, Lily J.; Rinne, Ethan; Van Natta, Bruce W.; Neumann, Colby R.; Mohan, Ganesh; Lester, Mary; VonDerHaar, R. Jason; German, Rana; Marino, Natascia; Hassanein, Aladdin H.; Gordillo, Gayle M.; Kaplan, Mark H.; Sen, Chandan K.; Kadin, Marshall E.; Sinha, Mithun; Surgery, School of Medicine
    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.
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    Immediate Lymphatic Reconstruction to Prevent Breast Cancer-Related Lymphedema: A Systematic Review
    (Liebert, 2022-04) Cook, Julia A.; Sinha, Mithun; Lester, Mary; Fisher, Carla S.; Sen, Chandan K.; Hassanein, Aladdin H.; Medicine, School of Medicine
    Significance: Lymphedema is chronic limb swelling from lymphatic dysfunction. The condition affects up to 250 million people worldwide. In breast cancer patients, lymphedema occurs in 30% who undergo axillary lymph node dissection (ALND). Recent Advances: Immediate lymphatic reconstruction (ILR), also termed Lymphatic Microsurgical Preventing Healing Approach (LyMPHA), is a method to decrease the risk of lymphedema by performing prophylactic lymphovenous anastomoses at the time of ALND. The objective of this study is to assess the risk reduction of ILR in preventing lymphedema. Critical Issues: Lymphedema has significant effects on the quality of life and morbidity of patients. Several techniques have been described to manage lymphedema after development, but prophylactic treatment of lymphedema with ILR may decrease risk of development to 6.6%. Future Directions: Long-term studies that demonstrate efficacy of ILR may allow for prophylactic management of lymphedema in the patient undergoing lymph node dissection.
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    Immunomodulatory Effects of Oxylipin 10-HOME Produced by Biofilm Results in Host-Biofilm Interaction in Breast Implant Illness
    (Wolters Kluwer, 2022) Khan Mohammed, Imran; Minto, Robert; Kelley-Patteson, Christine; Timsina, Lava; Singh, Kanhaiya; Van Natta, Bruce W.; Mohan, Ganesh; Chauhan, Ruvi; Lester, Mary; Hassanein, Al; Gordillo, Gayle M.; Sen, Chandan; Kadin, Marshall; Sinha, Mithun; Surgery, School of Medicine
    PURPOSE: The spread of biofilms on medical implants represents one of the principal triggers of persistent and chronic infections in clinical settings. Nearly 300,000 women annually have breast implant surgery in the United States, for reasons including post-mastectomy breast reconstruction, revision of prior augmentation/ reconstruction, cosmetic augmentation, and gender affirmation. There has been increased identification of patients experiencing a constellation of symptoms related to their implants termed as breast implant illness (BII). In this work, we report that bacterial biofilm associated with breast implant, metabolize fatty acid oleic acid present in the breast tissue milieu to oxylipins, one such oxylipin identified from this study is (E)-10-hydroxy-8-octadecenoic acid (10-HOME). We hypothesize that immunomodulatory effects of oxylipin 10-HOME produced by biofilm present on the implant could be a possible etiology for BII pathogenesis. METHOD: Implants, peri-prosthetic tissues and blood was collected from BII subjects (n=46) and two control groups, group I, (non-BII, n=34) patients with breast implants, no BII symptoms. Group II (normal tissue, n = 20), patients without an implant, whose breast tissue was removed due to surgical procedures. A questionnaire developed based on epidemiological studies on BII screened for the commonly reported symptoms associated with BII. Predictive variables included age, diabetes status, co-morbidities, type (smooth/textured) and duration of implant. Scanning electron microscopy (SEM), 16S rRNA (genomic) next generation sequencing (NGS) were used for bacterial biofilm identification. 10-HOME was quantitated through targeted and untargeted lipidomic analyses using LC-MS-MS. RNA-Seq analysis was performed on peri-prosthetic breast tissues. Flow cytometry and mass cytometry (CyToF) were conducted to investigate the role of immune cells. RESULTS: Bacterial biofilm was detected through SEM and 16SrRNA NGS. Bivariate analysis using cross-tabulation was performed between presence of biofilm and the study groups. Using the two-sample test of proportions with z-tests, Staphylococcus epidermidis colonization was observed to be higher in the BII group (73.33%) compared to non-BII group (16.67%, p=0.018) and the normal group (10%, p=0.036). The BII group was 2.4 times more likely to have S. epidermidis colonization compared to the non-BII group (Odds Ratio=2.4). Similarly, when comparing with normal group, the BII group was 3.4 times more likely to have S. epidermidis. Elevated levels of 10-HOME in BII compared to non-BII samples, (p<0.0001) were observed through mass spectrometry. Positive correlation was observed between bacterial abundance and concentration of 10-HOME in BII subjects (R2=0.88). RNA-Seq analysis on peri-prosthetic tissue and flow/ mass cytometry analyses from peripheral blood derived lymphocytes showed increased abundance of CD4+ Th1 cells. Th1 cells have been reported to be activated in auto-immune diseases. No significant difference was observed in the abundance of other Th subtypes (Th2, Th9 and Th22). Oxylipin 10-HOME polarized CD4+ naïve T cells to Th1 subtype in vitro. CONCLUSION: This study investigated the biofilm hypothesis of BII through a biofilm derived immunogenic metabolite. Through a systematic cause-effect based studies, the work shows activation of Th1 cells in presence of 10-HOME. The study provides the first evidence of a possible etiology of BII mediated via bacterial biofilm derived 10-HOME.
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    QS9: Host Biofilm Interaction In Breast Implant Illness
    (Wolters Kluwer, 2021-07) Khan, Imran; Minto, Robert E.; Kelley-Patteson, Christine; Van Natta, Bruce; Mohan, Ganesh; Suh, Lily; Singh, Kanhaiya; Lester, Mary; VonDerHaar, R. Jason; Gordillo, Gayle M.; Hassanein, Aladdin; Sen, Chandan K.; Kadin, Marshall E.; Sinha, Mithun; Surgery, School of Medicine
    Purpose: Breast Implant Illness (BII) is patient-described constellation of symptoms that are believed to be related to their breast implant. The symptoms described include fibromyalgia, chronic fatigue and a host of other symptoms that are often associated with autoimmune illnesses. In this work, we report that bacterial biofilm associated with breast implant, metabolize fatty acid oleic acid present in the breast tissue milieu to oxylipins, one such oxylipin identified from this study is (10S)-hydroxy-(8E)-octadecenoic acid (10-HOME). We hypothesize that immunomodulatory effects of oxylipin 10-HOME produced by biofilm present on the implant could be correlated with BII pathogenesis. Methods: Capsulectomy and breast implants from clinically indicated procedures for patients requesting prosthetic removal were collected using clinical parameters outlined in previous studies, and questionnaire screened for the commonly reported symptoms associated with BII. Predictive variables included age, diabetes status, co-morbidities, nature and duration of implant. Scanning electron microscopy (SEM), Wheat Germ Agglutinin (WGA) and 16SrRNA sequencing were used for bacterial biofilm bacterial identification. 10-HOME was quantitated through targeted and untargeted lipidomic analyses using LC-MS-MS. Results: Sixty eight Implant, associated capsules and breast tissue specimen were collected for BII (n=46) and two control groups, group I, (non-BII, n=14) patients with breast implants, no BII symptoms. Group II (normal tissue, n = 8), patients without an implant, whose breast tissue was removed due to surgical procedures. Bacterial biofilm was detected through SEM in both BII and non BII cohorts. However, WGA analysis (quantitative analysis) indicated increased abundance of biofilm in the BII cohort (n=7, p=0.0036). 16SrRNA (genomic) sequencing identified increased abundance of Staphylococcus epidermidis (Fisher’s exact test, p<0.001) in the BII group (63.04%) compared to non-BII group (14.3%) and the normal group. The BII group was 9.8 times significantly more likely to have Staphylococcus epidermidis colonization compared to the non-BII group (p=0.003, logistic regression), compared to normal, it is 17.4 times significantly more likely to have Staphylococcus epidermidis (p=0.0021). Elevated levels of 10-HOME BII compared to non-BII samples, (p < 0.0001) were observed through mass spectrometry. Positive correlation was observed between bacterial abundance and concentration of 10-HOME in BII subjects (R2=0.88). Similar correlation was observed in BII subjects with Staphylococcus epidermidis (R2=0.77). Conclusion: This study investigated the biofilm hypothesis of breast implant illness through a host-pathogen interaction. The breast microenvironment led to formation of biofilm derived 10-HOME from host oleic acid. The study provides the first evidence of a possible correlation between bacterial biofilm and biofilm derived 10-HOME in the context of 10-HOME. In consideration of reports of biofilm association with other metal implants, the findings of this study can possibly explain autoimmune response associated with those implants.