IL-10, IL-13, Eotaxin and IL-10/IL-6 ratio distinguish breast implant-associated anaplastic large-cell lymphoma from all types of benign late seromas

Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is an uncommon peripheral T cell lymphoma usually presenting as a delayed peri-implant effusion. Chronic inflammation elicited by the implant has been implicated in its pathogenesis. Infection or implant rupture may also be responsible for late seromas. Cytomorphological examination coupled with CD30 immunostaining and eventual T-cell clonality assessment are essential for BI-ALCL diagnosis. However, some benign effusions may also contain an oligo/monoclonal expansion of CD30 + cells that can make the diagnosis challenging. Since cytokines are key mediators of inflammation, we applied a multiplexed immuno-based assay to BI-ALCL seromas and to different types of reactive seromas to look for a potential diagnostic BI-ALCL-associated cytokine profile. We found that BI-ALCL is characterized by a Th2-type cytokine milieu associated with significant high levels of IL-10, IL-13 and Eotaxin which discriminate BI-ALCL from all types of reactive seroma. Moreover, we found a cutoff of IL10/IL-6 ratio of 0.104 is associated with specificity of 100% and sensitivity of 83% in recognizing BI-ALCL effusions. This study identifies promising biomarkers for initial screening of late seromas that can facilitate early diagnosis of BI-ALCL

Etiology of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL): Current Directions in Research

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a CD30-positive, anaplastic lymphoma kinase-negative T-cell lymphoma. Where implant history is known, all confirmed cases to date have occurred in patients with exposure to textured implants. There is a spectrum of disease presentation, with the most common occurring as a seroma with an indolent course. A less common presentation occurs as locally advanced or, rarely, as metastatic disease. Here we review the immunological characteristics of BIA-ALCL and potential triggers leading to its development. BIA-ALCL occurs in an inflammatory microenvironment with significant lymphocyte and plasma cell infiltration and a prominent Th1/Th17 phenotype in advanced disease. Genetic lesions affecting the JAK/STAT signaling pathway are commonly present. Proposed triggers for the development of malignancy include mechanical friction, silicone implant shell particulates, silicone leachables, and bacteria. Of these, the bacterial hypothesis has received significant attention, supported by a plausible biologic model. In this model, bacteria form an adherent biofilm in the favorable environment of the textured implant surface, producing a bacterial load that elicits a chronic inflammatory response. Bacterial antigens, primarily of Gram-negative origin, may trigger innate immunity and induce T-cell proliferation with subsequent malignant transformation in genetically susceptible individuals. Although much remains to be elucidated regarding the multifactorial origins of BIA-ALCL, future research should focus on prevention and treatment strategies, recognizing susceptible populations, and whether decreasing the risk of BIA-ALCL is possible

QS9: Host Biofilm Interaction In Breast Implant Illness

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

Biofilm Derived Oxylipin Mediated Autoimmune Response in Breast Implant Subjects

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

The JWST Early Release Science Program for Direct Observations of Exoplanetary Systems. IV. NIRISS Aperture Masking Interferometry Performance and Lessons Learned

We present a performance analysis for the aperture masking interferometry (AMI) mode on board the James Webb Space Telescope Near Infrared Imager and Slitless Spectrograph (JWST/NIRISS). Thanks to self-calibrating observables, AMI accesses inner working angles down to and even within the classical diffraction limit. The scientific potential of this mode has recently been demonstrated by the Early Release Science (ERS) 1386 program with a deep search for close-in companions in the HIP 65426 exoplanetary system. As part of ERS 1386, we use the same data set to explore the random, static, and calibration errors of NIRISS AMI observables. We compare the observed noise properties and achievable contrast to theoretical predictions. We explore possible sources of calibration errors and show that differences in charge migration between the observations of HIP 65426 and point-spread function calibration stars can account for the achieved contrast curves. Lastly, we use self-calibration tests to demonstrate that with adequate calibration NIRISS F380M AMI can reach contrast levels of ∼9–10 mag at ≳λ/D. These tests lead us to observation planning recommendations and strongly motivate future studies aimed at producing sophisticated calibration strategies taking these systematic effects into account. This will unlock the unprecedented capabilities of JWST/NIRISS AMI, with sensitivity to significantly colder, lower-mass exoplanets than lower-contrast ground-based AMI setups, at orbital separations inaccessible to JWST coronagraphy