A22-16 Characterisation of the Role of Mucosal-associated Invariant T Cells and Association With Clinical Features in Lymphangioleiomyomatosis

Abstract Rationale Lymphangioleiomyomatosis (LAM) is a rare, slow growing neoplasm, characterised by development of diffuse cystic lung disease. It affects women of child-bearing age predominantly, with lung parenchymal infiltration by abnormal LAM cells. LAM cells and their interaction with immune cells is poorly understood, with evidence of evasion of detection through mechanistic target of rapamycin (mTOR) dependent pathways. Innate T cell function may play a role, with infiltrated T cells surrounding lung LAM nodules. A subset, Mucosal-associated invariant T (MAIT) cells, potentially play a role in the LAM microenvironment. The aim of our study is to characterise MAIT cell function and examine correlation with markers of disease progression. Methods LAM patient and healthy control serum was collected for processing and analysis by flow cytometry. An immune cell panel consisting of CD45, Siglec8, CD14, CD15, CD19, CD3 and TCRva7.2 antibodies was used to identify MAIT cell populations. Further characterisation was carried out with a panel including TCRva7.2, CD161, CD4 and CD8 antibodies. Pulmonary function, VEGF-D levels and clinical characteristics, including treatment status, were collected for LAM cases. Statistical analysis was performed using GraphPad Prism, following application of a gating strategy to identify cell populations with FlowJo software. Results Reduced TCRva7.2 positive MAIT cells (p = 0.002) were evident in peripheral blood in LAM cases (n = 17) vs control (n = 14). Findings were maintained (p = 0.004) in untreated cases (n = 10). Investigation of MAIT cell CD4 and CD8 subsets for correlation with lung function was carried out. Associations between loss of both FEV1/ml (r2=0.527) and DLCO percentage (r2=0.423) over time with reduced CD4 MAIT cell counts, as well as loss of DLCO percentage (r2=0.429) over time with elevated CD8 MAIT cell counts were identified. MAIT cell CD4/CD8 ratio displayed an association with reduced ratios and loss of both FEV1/ml (r2=0.516) and DLCO percentage (r2=0.523) over time. LAM cases with elevated CD8 positive MAIT cells were more likely to be premenopausal (p = 0.048). In the untreated group MAIT cell CD4/CD8 subset profiles were similarly associated with lung function decline, while the treated subgroup did not reveal significant associations. Conclusions Reductions in peripheral MAIT cell counts are evident in LAM, with associations between LAM MAIT cell CD4/CD8 ratio and disease severity. Subpopulations of interest include untreated LAM and the predominance of lung function decline, as well as CD8 MAIT cell elevation in premenopausal cases, providing insights into populations exhibiting the greatest immune dysregulation. This abstract is funded by: None