PB1950: MASS CYTOMETRY ANALYSIS IDENTIFIES T CELL IMMUNE SIGNATURE FOR APLASTIC ANEMIA AND PREDICTS RESPONSE TO CYCLOSPORINE

Abstract

Background: Aplastic anemia (AA) is a bone marrow failure syndrome attacked by autologous T cells. Cyclosporine is often taken for non-severe AA which is accounting for 80% of AA. Although effective, the response rate to cyclosporine is only around 50%. Emerging data support that T cell subpopulations, expression of transcription factors and immune checkpoint molecules are critical to regulate pathophysiology of AA. It’s also verified that T cell egress and activation play an important role in autoimmune diseases. Aims: We hypothesis that defining T cell immune signature will facilitate the development of predicting cyclosporine response and exploring novel immune-based therapeutics. Methods: Here, we performed mass cytometry for phenotypic and functional immune analysis on clinical samples from AA patients receiving cyclosporine treatment and demonstrated a significant heterogeneity on expression of inhibitory molecules, T cell trafficking and cytokines. Results: T-cell expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) was upregulated following response to cyclosporine and a lower level of CTLA-4 on CD8+ T cells was correlated to better treatment response. Moreover, higher expression of sphingosine-1-phospharylation receptor 1 (S1P1) on naïve T cells and higher level of interleukin-9 (IL-9) on T helpers predicted a worse response to cyclosporine. Therefore, this immune signature has a strong predictive value for clinical response. Summary/Conclusion: Collectively, our study suggests that immune-based analysis may predict clinical response to cyclosporine and provide a therapeutic strategy to improve the treatment of AA.