Skip to main content
Top
Published in: Annals of Hematology 3/2023

21-01-2023 | Aplastic Anemia | Original Article

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

Authors: Lele Zhang, Jin Mao, Yu Lian, Qian Liang, Weiwang Li, Jingyu Zhao, Hong Pan, Zhen Gao, Liwei Fang, Weiping Yuan, Yajing Chu, Jun Shi

Published in: Annals of Hematology | Issue 3/2023

Login to get access

Abstract

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 (S1P1) 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, S1P1, 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.
Appendix
Available only for authorised users
Literature
4.
go back to reference Camitta BM, Rappeport JM, Parkman R, Nathan DG (1975) Selection of patients for bone marrow transplantation in severe aplastic anemia. Blood 45(3):355–363CrossRefPubMed Camitta BM, Rappeport JM, Parkman R, Nathan DG (1975) Selection of patients for bone marrow transplantation in severe aplastic anemia. Blood 45(3):355–363CrossRefPubMed
24.
go back to reference Holbrook ST, Ohls RK, Schibler KR, Yang YC, Christensen RD (1991) Effect of interleukin-9 on clonogenic maturation and cell-cycle status of fetal and adult hematopoietic progenitors. Blood 77(10):2129–2134CrossRefPubMed Holbrook ST, Ohls RK, Schibler KR, Yang YC, Christensen RD (1991) Effect of interleukin-9 on clonogenic maturation and cell-cycle status of fetal and adult hematopoietic progenitors. Blood 77(10):2129–2134CrossRefPubMed
29.
go back to reference Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC, British Society for Standards in H (2016) Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol 172(2):187–207. https://doi.org/10.1111/bjh.13853CrossRefPubMed Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC, British Society for Standards in H (2016) Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol 172(2):187–207. https://​doi.​org/​10.​1111/​bjh.​13853CrossRefPubMed
31.
go back to reference Lengline E, Drenou B, Peterlin P, Tournilhac O, Abraham J, Berceanu A, Dupriez B, Guillerm G, Raffoux E, de Fontbrune FS, Ades L, Balsat M, Chaoui D, Coppo P, Corm S, Leblanc T, Maillard N, Terriou L, Socié G, de Latour RP (2018) Nationwide survey on the use of eltrombopag in patients with severe aplastic anemia: a report on behalf of the French Reference Center for Aplastic Anemia. Haematologica 103(2):212–220. https://doi.org/10.3324/haematol.2017.176339CrossRefPubMedPubMedCentral Lengline E, Drenou B, Peterlin P, Tournilhac O, Abraham J, Berceanu A, Dupriez B, Guillerm G, Raffoux E, de Fontbrune FS, Ades L, Balsat M, Chaoui D, Coppo P, Corm S, Leblanc T, Maillard N, Terriou L, Socié G, de Latour RP (2018) Nationwide survey on the use of eltrombopag in patients with severe aplastic anemia: a report on behalf of the French Reference Center for Aplastic Anemia. Haematologica 103(2):212–220. https://​doi.​org/​10.​3324/​haematol.​2017.​176339CrossRefPubMedPubMedCentral
54.
go back to reference Gerlach K, Hwang Y, Nikolaev A, Atreya R, Dornhoff H, Steiner S, Lehr HA, Wirtz S, Vieth M, Waisman A, Rosenbauer F, McKenzie AN, Weigmann B, Neurath MF (2014) TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells. Nat Immunol 15(7):676–686. https://doi.org/10.1038/ni.2920CrossRefPubMed Gerlach K, Hwang Y, Nikolaev A, Atreya R, Dornhoff H, Steiner S, Lehr HA, Wirtz S, Vieth M, Waisman A, Rosenbauer F, McKenzie AN, Weigmann B, Neurath MF (2014) TH9 cells that express the transcription factor PU.1 drive T cell-mediated colitis via IL-9 receptor signaling in intestinal epithelial cells. Nat Immunol 15(7):676–686. https://​doi.​org/​10.​1038/​ni.​2920CrossRefPubMed
Metadata
Title
Mass cytometry analysis identifies T cell immune signature of aplastic anemia and predicts the response to cyclosporine
Authors
Lele Zhang
Jin Mao
Yu Lian
Qian Liang
Weiwang Li
Jingyu Zhao
Hong Pan
Zhen Gao
Liwei Fang
Weiping Yuan
Yajing Chu
Jun Shi
Publication date
21-01-2023
Publisher
Springer Berlin Heidelberg
Keyword
Aplastic Anemia
Published in
Annals of Hematology / Issue 3/2023
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-023-05097-6

Other articles of this Issue 3/2023

Annals of Hematology 3/2023 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Webinar | 06-02-2024 | 20:00 (CET)

Mastering chronic pancreatitis pain: A multidisciplinary approach and practical solutions

Severe pain is the most common symptom of chronic pancreatitis. In this webinar, experts share the latest insights in pain management for chronic pancreatitis patients. Experts from a range of disciplines discuss pertinent cases and provide practical suggestions for use within clinical practice.

Sponsored by: Viatris

Developed by: Springer Healthcare