Journal of Blood & Lymph

Silicone breast implants have been linked to the development of cancers such as Breast Implant Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL) and lesser understood conditions Breast Implant Illness (BII). The pathogenesis of BIA-ALCL has been linked to T-cell activation and proliferation in the capsule of textured breast implants. The effect of silicone breast implants on B cell-mediated immune reactions is not broadly understood. To cultivate a better understanding of how breast implants, affect B-cell mediated immune responses, both local in the capsule and potentially systemically, the authors performed a systematic review. After screening 1096 articles, 39 studies met inclusion criteria. Of the 39 studies meeting inclusion criteria, 23 studied human subjects, 14 studied animal models and 2 studied in vitro models. These studies focused on B cell-mediated immune responses on either a systemic level by examining antibody formation or on a local level by examining the breast implant capsule. Common results included the presence of anti-silicone antibodies and autoantibodies frequently implicated in autoimmune diseases. B lymphocytes found in the breast implant capsule were shown to form germinal centers and plasma cells, which secrete antibodies. Importantly, ten studies showed no indication that B cell-mediated immunity was significantly different in breast implant exposed subjects compared to those without implants. Exposure to silicone breast implants can result in B-cell mediated immune responses such as antibody formation. More research is needed to link these findings to the clinical manifestations of breast implant associated pathology.

Patients with severe uncontrolled asthma represent a distinct endotype with persistent airway inflammation and remodeling that is refractory to corticosteroid treatment. CD4⁺ T_H2 cells play a central role in regulating asthma pathogenesis, and biologic therapies targeting their cytokine pathways have had promising outcomes. However, not all patients respond well to such treatment, and their effects are not always durable nor reverse airway remodeling. This observation raises the possibility that other CD4⁺ T cell subsets and their effector molecules may drive airway inflammation and remodeling. We performed single-cell transcriptome analysis of >50,000 airway CD4⁺ T cells isolated from Bronchoalveolar Lavage (BAL) samples from 30 patients with mild and severe asthma. We observed striking heterogeneity in the nature of CD4⁺ T cells present in asthmatics' airways with Tissue-Resident Memory (T_RM ) cells making a dominant contribution. Notably, in severe asthmatics, a subset of CD4⁺ T_RM cells (CD103^-expressing) was significantly increased, comprising nearly 65% of all CD4⁺ T cells in the airways of male patients with severe asthma when compared to mild asthma (13%). This subset was enriched for transcripts linked to T Cell Receptor (TCR) activation (HLA-DRB1, HLA-DPA1) and cytotoxicity (GZMB, GZMA) and, following stimulation, expressed high levels of transcripts encoding for pro-inflammatory non-T_H2 cytokines (CCL3, CCL4, CCL5, TNF, LIGHT) that could fuel persistent airway inflammation and remodeling. Our findings indicate the need to look beyond the traditional T2 model of severe asthma to better understand the heterogeneity of this disease.