title: A CD8+ T cell transcription signature predicts prognosis in autoimmune disease.
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.
authors.affiliation: Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Eoin F
authors.initials: EF
authors.lastname: McKinney
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lyons
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Carr
authors.forename: Jane L
authors.initials: JL
authors.lastname: Hollis
authors.forename: David R W
authors.initials: DR
authors.lastname: Jayne
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Willcocks
authors.forename: Maria
authors.initials: M
authors.lastname: Koukoulaki
authors.forename: Alvis
authors.initials: A
authors.lastname: Brazma
authors.forename: Vojislav
authors.initials: V
authors.lastname: Jovanovic
authors.forename: D Michael
authors.initials: DM
authors.lastname: Kemeny
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
authors.forename: Paul A
authors.initials: PA
authors.lastname: Macary
authors.forename: Afzal N
authors.initials: AN
authors.lastname: Chaudhry
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014657:Vasculitis / Q000188:drug therapy / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D007166:Immunosuppressive Agents; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell
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