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Identification of activated cytokine pathways in the blood of systemic lupus erythematosus, myositis, rheumatoid arthritis, and scleroderma patients
Author(s) -
HIGGS Brandon W.,
ZHU Wei,
RICHMAN Laura,
FIORENTINO David F.,
GREENBERG Steven A.,
JALLAL Bahija,
YAO Yihong
Publication year - 2012
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/j.1756-185x.2011.01654.x
Subject(s) - medicine , immunology , rheumatoid arthritis , cytokine , dermatomyositis , polymyositis , tumor necrosis factor alpha , interleukin 23 , etanercept , interleukin
Aim: To develop genomic signatures of seven cytokines involved in the pathogenesis of rheumatic diseases such as systemic lupus erythematosus (SLE), dermatomyositis (DM), polymyositis (PM), rheumatoid arthritis (RA), or systemic scleroderma (SSc) that could potentially help identify patients likely to respond to therapies that target these individual cytokines.Methods: Over‐expressed transcripts in the whole blood (WB) were identified from 262 SLE, 44 DM, 33 PM, 38 SSc and 89 RA subjects and compared to 24 healthy subjects using Affymetrix arrays. Cytokine‐inducible gene signatures such as type I interferon (IFN), tumor necrosis factor alpha (TNF‐α), interleukin (IL)‐1β, IL‐10, IL‐13, IL‐17, and granulosyte–macrophage colony‐stimulating factor (GM‐CSF) were assessed in the WB of these subjects to identify subpopulations showing activation of specific cytokine pathways.Results: Significant activation of the type I IFN pathway in a population of five diseases studied was universally observed. The TNF‐α and IL‐1β pathways were activated in subgroups of PM and RA subjects, respectively, with another subgroup of RA subjects showing activation of the IL‐13 pathway. The GM‐CSF pathway was activated in a subgroup of SSc subjects and the IL‐17 pathway was activated in subgroups of all diseases except SLE.Conclusions: A novel gene expression measurement of activated cytokines in five different rheumatic diseases is presented. Characterizing the cytokine pathways most activated in specific patient subpopulations has the potential to help target the appropriate patient populations for corresponding anti‐cytokine therapies.