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

Rheumatology (Oxford). 2010 Oct;49(10):1867-77. doi: 10.1093/rheumatology/keq151. Epub 2010 Jun 29.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • B-Cell Activating Factor / immunology*
  • Chemokines / immunology*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cytokines / immunology*
  • European Continental Ancestry Group
  • Female
  • Humans
  • Ligands
  • Male
  • Middle Aged
  • Models, Immunological
  • Myositis / immunology*
  • Tumor Necrosis Factor-alpha
  • Young Adult

Substances

  • B-Cell Activating Factor
  • Chemokines
  • Cytokines
  • Ligands
  • Tumor Necrosis Factor-alpha