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; Neal S Young

doi:10.1038/s41467-025-60213-6

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, Neal S Young

Comprehensive Cancer Centre

Research output: Contribution to journal › Article › peer-review

16 Downloads (Pure)

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.

Original language	English
Article number	5048
Journal	Nature Communications
Volume	16
Issue number	1
Early online date	30 May 2025
DOIs	https://doi.org/10.1038/s41467-025-60213-6
Publication status	E-pub ahead of print - 30 May 2025

Keywords

Humans
Anemia, Aplastic/immunology
Autoimmunity/immunology
Single-Cell Analysis/methods
Immunotherapy/methods
T-Lymphocytes, Cytotoxic/immunology
Female
Myeloid Cells/immunology
Male
Interferon-gamma/immunology
Adult
Hematopoietic Stem Cells/immunology

Access to Document

10.1038/s41467-025-60213-6Licence: CC BY

Human autoimmunity at single_WU_Publishedonline30May2025_GOLD_VoR (CC BY)Final published version, 4.02 MBLicence: CC BY

Cite this

Wu, Z., Gao, S., Feng, X., Li, H., Sompairac, N., Jamshidi, S., Choy, D., Reis, R. A. D., Gao, Q., Kajigaya, S., Alemu, L., Raffo, D. Q., Groarke, E. M., Kordasti, S., Patel, B. A., & Young, N. S. (2025). Human autoimmunity at single cell resolution in aplastic anemia before and after effective immunotherapy. Nature Communications, 16(1), Article 5048. Advance online publication. https://doi.org/10.1038/s41467-025-60213-6

@article{d00ac4ee7f7f49bdbb40eac7c9039e95,

title = "Human autoimmunity at single cell resolution in aplastic anemia before and after effective immunotherapy",

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.",

keywords = "Humans, Anemia, Aplastic/immunology, Autoimmunity/immunology, Single-Cell Analysis/methods, Immunotherapy/methods, T-Lymphocytes, Cytotoxic/immunology, Female, Myeloid Cells/immunology, Male, Interferon-gamma/immunology, Adult, Hematopoietic Stem Cells/immunology",

author = "Zhijie Wu and Shouguo Gao and Xingmin Feng and Haoran Li and Nicolas Sompairac and Shirin Jamshidi and Desmond Choy and Reis, {Rita Antunes Dos} and Qingyan Gao and Sachiko Kajigaya and Lemlem Alemu and Raffo, {Diego Quinones} and Groarke, {Emma M} and Shahram Kordasti and Patel, {Bhavisha A} and Young, {Neal S}",

note = "Publisher Copyright: {\textcopyright} This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2025.",

year = "2025",

month = may,

day = "30",

doi = "10.1038/s41467-025-60213-6",

language = "English",

volume = "16",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

TY - JOUR

T1 - Human autoimmunity at single cell resolution in aplastic anemia before and after effective immunotherapy

AU - Wu, Zhijie

AU - Gao, Shouguo

AU - Feng, Xingmin

AU - Li, Haoran

AU - Sompairac, Nicolas

AU - Jamshidi, Shirin

AU - Choy, Desmond

AU - Reis, Rita Antunes Dos

AU - Gao, Qingyan

AU - Kajigaya, Sachiko

AU - Alemu, Lemlem

AU - Raffo, Diego Quinones

AU - Groarke, Emma M

AU - Kordasti, Shahram

AU - Patel, Bhavisha A

AU - Young, Neal S

N1 - Publisher Copyright: © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2025.

PY - 2025/5/30

Y1 - 2025/5/30

N2 - 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.

AB - 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.

KW - Humans

KW - Anemia, Aplastic/immunology

KW - Autoimmunity/immunology

KW - Single-Cell Analysis/methods

KW - Immunotherapy/methods

KW - T-Lymphocytes, Cytotoxic/immunology

KW - Female

KW - Myeloid Cells/immunology

KW - Male

KW - Interferon-gamma/immunology

KW - Adult

KW - Hematopoietic Stem Cells/immunology

UR - http://www.scopus.com/inward/record.url?scp=105006903413&partnerID=8YFLogxK

U2 - 10.1038/s41467-025-60213-6

DO - 10.1038/s41467-025-60213-6

M3 - Article

C2 - 40447607

SN - 2041-1723

VL - 16

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5048

ER -

Human autoimmunity at single cell resolution in aplastic anemia before and after effective immunotherapy

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this