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A CD8+ T cell transcription signature predicts prognosis in autoimmune disease

Open access
McKinney, Eoin F, Lyons, Paul A, Carr, Edward J, Hollis, Jane L, Jayne, David R W, Willcocks, Lisa C, Koukoulaki, Maria, Brazma, Alvis, Jovanovic, Vojislav, Kemeny, D Michael, Pollard, Andrew J, MacAry, Paul A, Chaudhry, Afzal N, Smith, Kenneth G C·2010·Nature Medicine

Abstract

Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of potentially toxic immunosuppressive therapy. Gene expression–based biomarkers facilitating such tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice. We show that transcriptional profiling of purified CD8+ T cells, which avoids the confounding influences of unseparated cells, identifies two distinct subject subgroups predicting long-term prognosis in two autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium-sized and small blood vessels, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction. We show that the subset of genes defining the poor prognostic group is enriched for genes involved in the interleukin-7 receptor (IL-7R) pathway and T cell receptor (TCR) signaling and those expressed by memory T cells. Furthermore, the poor prognostic group is associated with an expanded CD8+ T cell memory population. These subgroups, which are also found in the normal population and can be identified by measuring expression of only three genes, raise the prospect of individualized therapy and suggest new potential therapeutic targets in autoimmunity.

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Metadata

Authors
McKinney, E. F., Lyons, P. A., Carr, E. J., Hollis, J. L., Jayne, D. R. W., Willcocks, L. C., Koukoulaki, M., Brazma, A., Jovanovic, V., Kemeny, D. M., Pollard, A. J., MacAry, P. A., Chaudhry, A. N., & Smith, K. G. C.
Venue
Nature Medicine
Published
2010-04-18
Volume
16
Issue
5
Pages
586-591
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2092644774
Cited by
370
References
5
FWCI
18.47
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. https://app.cochat.ai/papers/10.1038/nm.2130
The paper
McKinney, E. F., Lyons, P. A., Carr, E. J., Hollis, J. L., Jayne, D. R. W., Willcocks, L. C., Koukoulaki, M., Brazma, A., Jovanovic, V., Kemeny, D. M., Pollard, A. J., MacAry, P. A., Chaudhry, A. N., & Smith, K. G. C. (2010). A CD8+ T cell transcription signature predicts prognosis in autoimmune disease. Nature Medicine. https://doi.org/10.1038/nm.2130

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.