Mass cytometry analysis identifies T cell immune signature of aplastic anemia and predicts the response to cyclosporine

Aplastic anemia (AA) is an auto-activated T cell–mediated bone marrow failure. Cyclosporine is often used to treat non-severe AA, which demonstrates a more heterogeneous condition than severe AA. The response rate to cyclosporine is only around 50% in non-severe AA. To better predict response to cyclosporine and pinpoint who is the appropriate candidate for cyclosporine, we performed phenotypic and functional T cell immune signature at single cell level by mass cytometry from 30 patients with non-severe AA. Unexpectedly, non-significant differences of T cell subsets were observed between AA and healthy control or cyclosporine-responder and non-responders. Interestingly, when screening the expression of co-inhibitory molecules, T cell trafficking mediators, and cytokines, we found an increase of cytotoxic T lymphocyte antigen 4 (CTLA-4) on T cells in response to cyclosporine and a lower level of CTLA-4 on CD8(+) T cells was correlated to hematologic response. Moreover, a decreased expression of sphingosine-1-phosphate receptor 1 (S1P(1)) on naive T cells and a lower level of interleukin-9 (IL-9) on T helpers also predicted a better response to cyclosporine, respectively. Therefore, the T cell immune signature, especially in CTAL-4, S1P(1), and IL-9, has a predictive value for response to cyclosporine. Collectively, our study implies that immune signature analysis of T cell by mass cytometry is a useful tool to make a strategic decision on cyclosporine treatment of AA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00277-023-05097-6.