TY - JOUR
T1 - Idiopathic inflammatory myopathies, signified by distinctive peripheral cytokines, chemokines and the TNF family members B-cell activating factor and a proliferation inducing ligand
AU - Szodoray, Peter
AU - Alex, Philip
AU - Knowlton, Nicholas
AU - Centola, Michael
AU - Dozmorov, Igor
AU - Csipo, Istvan
AU - Nagy, Annamaria T.
AU - Constantin, Tamas
AU - Ponyi, Andrea
AU - Nakken, Britt
AU - Danko, Katalin
N1 - Funding Information:
Funding: This work was supported by: NIH Ruth L. Kirschstein National Research Service Award, National Institutes of Health (NIH) grants 5U19AI062629, P20RR15577 and from Hungary the National Scientific Research Fund: TO46931 and Medical Research Council: 1F1KC00004/320.
PY - 2010/6/29
Y1 - 2010/6/29
N2 - 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.
AB - 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.
KW - A proliferation inducing ligand
KW - B-cell activating factor
KW - Circulating cytokines
KW - Idiopathic inflammatory myopathies
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U2 - 10.1093/rheumatology/keq151
DO - 10.1093/rheumatology/keq151
M3 - Article
C2 - 20591831
AN - SCOPUS:77956857329
SN - 1462-0324
VL - 49
SP - 1867
EP - 1877
JO - Rheumatology
JF - Rheumatology
IS - 10
M1 - keq151
ER -