Systemic immune dysregulation in patients experiencing urogynaecological mesh failure

Objectives: This study aimed to investigate the systemic immune landscape in patients experiencing urogynaecological mesh failure. The use of urogynaecological mesh was paused in the UK following an independent safety review that found ~1 in 15 women required removal due to complications. However, the mechanisms underpinning mesh failure remain largely unknown, with few studies focussing on localised tissue responses and no reports characterising systemic immune dysregulation. Materials and methods: Serum samples collected from patients during mesh removal surgery were analysed for immunomodulatory protein content using enzyme-linked immunosorbent assay (ELISA) and multiplex Luminex Discovery Assay. Peripheral blood mononuclear cells (PBMCs) collected were cultured with or without exposure to pristine mesh, and immunomodulatory protein secretion was measured in the same way. Patient serum was also used as a migratory stimulus for healthy PBMCs to test the functionality of chemotactic proteins present. Results: Mesh patient serum had increased chemotactic protein levels, particularly CCL2, CXCL5, CCL12 and CCL4, which had a functional effect and induced significant cell migration. Mesh patient PBMCs also secreted immunomodulatory proteins including MMP-9 and CCL2. Future studies should focus on expanding cohort numbers and including a control group of mesh patients not experiencing complications to further determine both underlying biology and mesh responses. Conclusions: This study characterised an altered systemic immune landscape not previously investigated in mesh failure patients. Clinically, the ability to identify phenotypic factors or develop biomarkers which predict and monitor mesh responses would help guide clinicians and patients in shared decision making.