title: CD8+ T Cells Specific to Apoptosis-Associated Antigens Predict the Response to Tumor Necrosis Factor Inhibitor Therapy in Rheumatoid Arthritis.
abstract: CD8+ T cells specific to caspase-cleaved antigens derived from apoptotic T cells (apoptotic epitopes) represent a principal player in chronic immune activation, which is known to amplify immunopathology in various inflammatory diseases. The purpose of the present study was to investigate the relationship involving these autoreactive T cells, the rheumatoid arthritis immunopathology, and the response to tumor necrosis factor-α inhibitor therapy. The frequency of autoreactive CD8+ T cells specific to various apoptotic epitopes, as detected by both enzyme-linked immunospot assay and dextramers of major histocompatibility complex class I molecules complexed with relevant apoptotic epitopes, was longitudinally analyzed in the peripheral blood of rheumatoid arthritis patients who were submitted to etanercept treatment (or other tumor necrosis factor inhibitors as a control). The percentage of apoptotic epitope-specific CD8+ T cells was significantly higher in rheumatoid arthritis patients than in healthy donors, and correlated with the disease activity. More important, it was significantly more elevated in responders to tumor necrosis factor-α inhibitor therapy than in non-responders before the start of therapy; it significantly dropped only in the former following therapy. These data indicate that apoptotic epitope-specific CD8+ T cells may be involved in rheumatoid arthritis immunopathology through the production of inflammatory cytokines and that they may potentially represent a predictive biomarker of response to tumor necrosis factor-α inhibitor therapy to validate in a larger cohort of patients.
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Citro
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Scrivo
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Helene
authors.initials: H
authors.lastname: Martini
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Martire
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: De Marzio
authors.affiliation: Dipartimento di Sanità Pubblica e Malattie Infettive, Sapienza Università di Roma, Rome, Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Vestri
authors.affiliation: La Jolla Institute for Allergy and Immunology, San Diego, California 92121, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.affiliation: La Jolla Institute for Allergy and Immunology, San Diego, California 92121, United States of America.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Viale del Policlinico 155, 00161 Rome, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti, 00185 Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barnaba
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
mesh_terms: D000941:Antigens / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000068800:Etanercept / Q000627:therapeutic use*; D006801:Humans; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000941:Antigens; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept