A CD8 T cell transcription signature predicts prognosis in autoimmune disease

Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of the potentially toxic immunosuppressive therapy required for their control. Gene expression-based biomarkers facilitating individual tailori...

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Main Authors:	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.
Format:	Online
Language:	English
Published:	2010
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504359/

id	pubmed-3504359
recordtype	oai_dc
spelling	pubmed-35043592012-11-22 A CD8 T cell transcription signature predicts prognosis in autoimmune disease 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. Article Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of the potentially toxic immunosuppressive therapy required for their control. Gene expression-based biomarkers facilitating individual tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice1,2. We show that transcriptional profiling of purified CD8 T cells, which avoids the confounding influences of unseparated cells3,4, identifies two distinct patient subgroups predicting long-term prognosis in two different autoimmune diseases, anti-neutrophil cytoplasmic antibody (ANCA) – associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium and small blood vessels5, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction6. We show that genes defining the poor prognostic group are enriched for genes of the IL7R pathway, TCR signalling 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 novel potential therapeutic targets in autoimmunity. 2010-04-18 2010-05 /pmc/articles/PMC3504359/ /pubmed/20400961 http://dx.doi.org/10.1038/nm.2130 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	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.
spellingShingle	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. A CD8 T cell transcription signature predicts prognosis in autoimmune disease
author_facet	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.
author_sort	McKinney, Eoin F.
title	A CD8 T cell transcription signature predicts prognosis in autoimmune disease
title_short	A CD8 T cell transcription signature predicts prognosis in autoimmune disease
title_full	A CD8 T cell transcription signature predicts prognosis in autoimmune disease
title_fullStr	A CD8 T cell transcription signature predicts prognosis in autoimmune disease
title_full_unstemmed	A CD8 T cell transcription signature predicts prognosis in autoimmune disease
title_sort	cd8 t cell transcription signature predicts prognosis in autoimmune disease
description	Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of the potentially toxic immunosuppressive therapy required for their control. Gene expression-based biomarkers facilitating individual tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into clinical practice1,2. We show that transcriptional profiling of purified CD8 T cells, which avoids the confounding influences of unseparated cells3,4, identifies two distinct patient subgroups predicting long-term prognosis in two different autoimmune diseases, anti-neutrophil cytoplasmic antibody (ANCA) – associated vasculitis (AAV), a chronic, severe disease characterized by inflammation of medium and small blood vessels5, and systemic lupus erythematosus (SLE), characterized by autoantibodies, immune complex deposition and diverse clinical manifestations ranging from glomerulonephritis to neurological dysfunction6. We show that genes defining the poor prognostic group are enriched for genes of the IL7R pathway, TCR signalling 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 novel potential therapeutic targets in autoimmunity.
publishDate	2010
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504359/
_version_	1611934664693383168

A CD8 T cell transcription signature predicts prognosis in autoimmune disease

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