title: Divergent gene activation in peripheral blood and tissues of patients with rheumatoid arthritis, psoriatic arthritis and psoriasis following infliximab therapy.
abstract: OBJECTIVE
  The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases.
  
  
  METHODS
  Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment. Paired synovial (n=3, RA, PsA) and skin biopsies (n=5, Ps) were also collected. Gene expression was analyzed by microarrays.
  
  
  RESULTS
  26 out of 31 subjects responded to IFX. The transcriptional response of CD14+ cells to IFX was unique for the three diseases, with little overlap (<25%) in significantly changed gene lists (with PsA having the largest number of changed genes). In Ps, altered gene expression was more pronounced in lesional skin (relative to paired, healthy skin) compared to blood (relative to healthy controls). Marked suppression of up-regulated genes in affected skin was noted 2 weeks after therapy but the expression patterns differed from uninvolved skin. Divergent patterns of expression were noted between the blood cells and skin or synovial tissues in individual patients. Functions that promote cell differentiation, proliferation and apoptosis in all three diseases were enriched. RA was enriched in functions in CD14- cells, PsA in CD14+ cells and Ps in both CD14+ and CD14- cells, however, the specific functions showed little overlap in the 3 disorders.
  
  
  CONCLUSIONS
  Divergent patterns of altered gene expression are observed in RA, PsA and Ps patients in blood cells and target organs in IFX responders. Differential gene expression profiles in the blood do not correlate with those in target organs.
authors.affiliation: Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Rosenberg
authors.affiliation: Janssen Research and Development LLC, Spring House, PA, United States of America.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Fan
authors.affiliation: Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, United States of America.
authors.forename: Yahui G
authors.initials: YG
authors.lastname: Chiu
authors.affiliation: Janssen Research and Development LLC, Spring House, PA, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bolce
authors.affiliation: Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, United States of America.
authors.forename: Darren
authors.initials: D
authors.lastname: Tabechian
authors.affiliation: Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, United States of America.
authors.forename: Rick
authors.initials: R
authors.lastname: Barrett
authors.affiliation: Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, United States of America.
authors.forename: Sharon
authors.initials: S
authors.lastname: Moorehead
authors.affiliation: Janssen Research and Development LLC, Spring House, PA, United States of America.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baribaud
authors.affiliation: Janssen Research and Development LLC, Spring House, PA, United States of America.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Janssen Research and Development LLC, Spring House, PA, United States of America.
authors.forename: Nancy
authors.initials: N
authors.lastname: Peffer
authors.affiliation: Janssen Research and Development LLC, Spring House, PA, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Shealy
authors.affiliation: The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, United States of America.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
authors.affiliation: Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, United States of America; The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, United States of America.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Ritchlin
mesh_terms: D000328:Adult; D015535:Arthritis, Psoriatic / Q000235:genetics* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D014644:Genetic Variation; D006801:Humans; D000069285:Infliximab / Q000009:adverse effects*; D008875:Middle Aged; D014176:Protein Biosynthesis; D011565:Psoriasis / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab