Transcriptome of capsular contracture around breast implants mimics allograft rejection: a matched case-control study

Background: Capsular contracture is a frequent and severe complication following breast implant surgery. Although several theories on the pathophysiology exist, the exact molecular mechanisms remain unclear. This study aimed to identify the specific genes, signaling pathways, and immune cells associated with capsular contracture. Methods: Breast implant capsule biopsies were collected from women undergoing implant replacement after breast augmentation. Patients with capsular contracture (Baker III/IV) and healthy controls (Baker I) were included in equal numbers and matched based on implant brand, surface, plane, and rupture status. Whole transcriptome RNA-sequencing was used for gene expression profiling. Results: We analyzed biopsies from 51 breasts of 50 women, revealing 1,500 differentially expressed genes based on capsular contracture status. Our findings revealed that capsular contracture signaling pathways mimic allograft rejection with activation of both the innate immune system (e.g., IL1A/B, CXCl9, TREML4, CR1) and the adaptive immune system (e.g., CD80 and IFN-γ). Capsular contracture was associated with increased expression of macrophages, CD4+ T cells, B cells, and plasma cells with upregulation of several immunoglobulin genes (e.g., IGHD/IGHE). Moreover, several fibrosis-related genes were significantly upregulated (e.g., MMP1, MMP1, MMP12) and downregulated (TIMP4) in breasts with capsular contracture. Conclusions: The results indicate that B cells play a more crucial role in the development of capsular contracture than previously assumed. The disease mechanism resembles allograft rejection, indicating that capsular contracture is a form of immunological rejection of the breast implant. Clinical Relevance Statement This study identified key genes associated with capsular contracture, suggesting new drug candidates e.g., MMP1 inhibitors to improve breast implant surgery outcomes. Synergizing research on allograft rejection and capsular contracture could also lead to new treatment strategies.