Human autoimmunity at single cell resolution in aplastic anemia before and after effective immunotherapy
Zhijie Wu (),
Shouguo Gao,
Xingmin Feng,
Haoran Li,
Nicolas Sompairac,
Shirin Jamshidi,
Desmond Choy,
Rita Antunes Dos Reis,
Qingyan Gao,
Sachiko Kajigaya,
Lemlem Alemu,
Diego Quinones Raffo,
Emma M. Groarke,
Shahram Kordasti,
Bhavisha A. Patel and
Neal S. Young
Additional contact information
Zhijie Wu: National Institutes of Health
Shouguo Gao: National Institutes of Health
Xingmin Feng: National Institutes of Health
Haoran Li: National Institutes of Health
Nicolas Sompairac: King’s College London
Shirin Jamshidi: King’s College London
Desmond Choy: King’s College London
Rita Antunes Dos Reis: King’s College London
Qingyan Gao: National Institutes of Health
Sachiko Kajigaya: National Institutes of Health
Lemlem Alemu: National Institutes of Health
Diego Quinones Raffo: National Institutes of Health
Emma M. Groarke: National Institutes of Health
Shahram Kordasti: King’s College London
Bhavisha A. Patel: National Institutes of Health
Neal S. Young: National Institutes of Health
Nature Communications, 2025, vol. 16, issue 1, 1-21
Abstract:
Abstract Severe immune aplastic anemia is a fatal disease due to the destruction of marrow hematopoietic cells by cytotoxic lymphocytes, serving as a paradigm for marrow failure syndromes and autoimmune diseases. To better understand its pathophysiology, we apply advanced single cell methodologies, including mass cytometry, single-cell RNA, and TCR/BCR sequencing, to patient samples from a clinical trial of immunosuppression and growth factor stimulation. We observe opposing changes in the abundance of myeloid cells and T cells, with T cell clonal expansion dominated by effector memory cells. Therapy reduces and suppresses cytotoxic T cells, but new T cell clones emerge hindering robust hematopoietic recovery. Enhanced cell-cell interactions including between hematopoietic cells and immune cells, in particular evolving IFNG and IFNGR, are noted in patients and are suppressed post-therapy. Hematologic recovery occurs with increases in the progenitor rather than stem cells. Genetic predispositions linked to immune activation genes enhances cytotoxic T cell activity and crosstalk with target cells.
Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60213-6
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DOI: 10.1038/s41467-025-60213-6
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