Single-cell analysis of aplastic anemia reveals a convergence of NK and NK-like CD8 T cells with a disease-associated TCR signature

S Lundgren; J Huuhtanen; M Keränen; X Feng; BA Patel; GL Ryland; LC Fox; C Bravo-Perez; M Clemente; C Kerr; G Walldin; O Dufva; Y Zaimoku; T Tuononen; M Myllymäki; F Ebeling; E Jokinen; M Heinonen; T Kasanen; J Klievink; H Lähteenmäki; T Jaatinen; S Kytölä; S Siitonen; A Dulau-Florea; R Braylan; M Heinäniemi; S Nakao; E Hellström-Lindberg; JP Maciejewski; P Blombery; NS Young; H Lähdesmäki; S Mustjoki

Journal article

Single-cell analysis of aplastic anemia reveals a convergence of NK and NK-like CD8 T cells with a disease-associated TCR signature

S Lundgren, J Huuhtanen, M Keränen, X Feng, BA Patel, GL Ryland, LC Fox, C Bravo-Perez, M Clemente, C Kerr, G Walldin, O Dufva, Y Zaimoku, T Tuononen, M Myllymäki, F Ebeling, E Jokinen, M Heinonen, T Kasanen, J Klievink Show all

Science Translational Medicine | American Association for the Advancement of Science | Published : 2025

DOI: 10.1126/scitranslmed.adl6758

Abstract

Immune aplastic anemia (AA) is a life-threatening bone marrow failure disorder driven by an autoimmune T cell attack against hematopoietic stem and progenitor cells (HSPCs). However, the exact autoantigen targets and role of other immune cells in the pathogenesis of AA are unknown. Here, we analyzed a cohort of 218 patients with AA using single-cell RNA and T cell receptor (TCR) αβ sequencing, TCRβ sequencing, flow cytometry, and plasma cytokine profiling. We identified natural killer (NK) cells and CD8+ terminally differentiated effector T (TEMRA) cells expressing NK receptors with AA-associated TCRβ motifs as the most dysregulated immune cell populations in AA bone marrow. Functional cocul..

View full abstract