Idiopathic inflammatory myopathies, signified by distinctive peripheral cytokines, chemokines and the TNF family members B-cell activating factor and a proliferation inducing ligand

Peter Szodoray, Philip Alex, Nicholas Knowlton, Michael Centola, Igor Dozmorov, Istvan Csipo, Annamaria T. Nagy, Tamas Constantin, Andrea Ponyi, Britt Nakken, Katalin Danko

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Objective. Serum cytokines play an important role in the pathogenesis of myositis by initiating and perpetuating various cellular and humoral autoimmune processes. The aim of the present study was to describe a broad spectrum of T-and B-cell cytokines, growth factors and chemokines in patients with idiopathic inflammatory myopathies (IIMs) and healthy individuals.Methods. A protein array system, denoted as multiplex cytokine assay was utilized to measure simultaneously the levels of 24 circulating cytokines, including B-cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) of patients with IIMs and healthy individuals. Additionally, correlational clustering and discriminant function analysis (DFA), two multivariate, supervised analysis methods were employed to identify a subset of biomarkers in order to describe potential functional interrelationships among these pathological cytokines. Results. Univariate analysis demonstrated that a complex set of immune and inflammatory modulating cytokines are significantly up-regulated in patients with IIMs relative to unaffected controls including IL-10, IL-13, IFN-α, epidermal growth factor (EGF), VEGF, fibroblast growth factor (FGF), CCL3 [macrophage inflammatory protein (MIP-1α)], CCL4 (MIP-1β) and CCL11 (eotaxin), whereas G-CSF was significantly reduced in IIM patients. Correlational clustering was able to discriminate between, and hence sub-classify patients with IIMs. DFA identified EGF, IFN-α, VEGF, CCL3 (MIP-1α) and IL-12p40, as analytes with the strongest discriminatory power among various myositis patients and controls.Conclusions. Our findings suggest that these factors modulate myositis pathology and help to identify differences between subsets of the disease.

Original languageEnglish (US)
Article numberkeq151
Pages (from-to)1867-1877
Number of pages11
JournalRheumatology
Volume49
Issue number10
DOIs
StatePublished - Jun 29 2010

Keywords

  • A proliferation inducing ligand
  • B-cell activating factor
  • Circulating cytokines
  • Idiopathic inflammatory myopathies

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

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