PMID- 20400961
OWN - NLM
STAT- MEDLINE
DCOM- 20100702
LR  - 20220408
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 16
IP  - 5
DP  - 2010 May
TI  - A CD8+ T cell transcription signature predicts prognosis in autoimmune disease.
PG  - 586-91, 1p following 591
LID - 10.1038/nm.2130 [doi]
AB  - 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.
FAU - McKinney, Eoin F
AU  - McKinney EF
AD  - Department of Medicine, University of Cambridge School of Clinical Medicine, 
      Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, UK.
FAU - Lyons, Paul A
AU  - Lyons PA
FAU - Carr, Edward J
AU  - Carr EJ
FAU - Hollis, Jane L
AU  - Hollis JL
FAU - Jayne, David R W
AU  - Jayne DR
FAU - Willcocks, Lisa C
AU  - Willcocks LC
FAU - Koukoulaki, Maria
AU  - Koukoulaki M
FAU - Brazma, Alvis
AU  - Brazma A
FAU - Jovanovic, Vojislav
AU  - Jovanovic V
FAU - Kemeny, D Michael
AU  - Kemeny DM
FAU - Pollard, Andrew J
AU  - Pollard AJ
FAU - Macary, Paul A
AU  - Macary PA
FAU - Chaudhry, Afzal N
AU  - Chaudhry AN
FAU - Smith, Kenneth G C
AU  - Smith KG
LA  - eng
GR  - 079895/WT_/Wellcome Trust/United Kingdom
GR  - G0400929/MRC_/Medical Research Council/United Kingdom
GR  - 083650/WT_/Wellcome Trust/United Kingdom
GR  - 16305/ARC_/Arthritis Research UK/United Kingdom
GR  - G0400929(71747)/MRC_/Medical Research Council/United Kingdom
GR  - 083650/Z/07/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100418
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Antibodies, Antineutrophil Cytoplasmic)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-7)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
CIN - Nat Rev Rheumatol. 2010 Jul;6(7):380. PMID: 20614501
MH  - Antibodies, Antineutrophil Cytoplasmic/immunology
MH  - Autoimmune Diseases/*drug therapy/*immunology
MH  - Autoimmunity/immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cohort Studies
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression
MH  - Humans
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Inflammation/drug therapy/immunology
MH  - Interleukin-7/immunology
MH  - Lupus Erythematosus, Systemic/drug therapy/immunology
MH  - Prognosis
MH  - Receptors, Antigen, T-Cell/immunology
MH  - Signal Transduction/immunology
MH  - T-Lymphocytes/*immunology
MH  - Vasculitis/drug therapy/immunology
PMC - PMC3504359
MID - EMS29061
OID - NLM: EMS29061
EDAT- 2010/04/20 06:00
MHDA- 2010/07/03 06:00
PMCR- 2012/11/22
CRDT- 2010/04/20 06:00
PHST- 2009/07/08 00:00 [received]
PHST- 2010/03/05 00:00 [accepted]
PHST- 2010/04/20 06:00 [entrez]
PHST- 2010/04/20 06:00 [pubmed]
PHST- 2010/07/03 06:00 [medline]
PHST- 2012/11/22 00:00 [pmc-release]
AID - nm.2130 [pii]
AID - 10.1038/nm.2130 [doi]
PST - ppublish
SO  - Nat Med. 2010 May;16(5):586-91, 1p following 591. doi: 10.1038/nm.2130. Epub 2010 
      Apr 18.