Idiopathic inflammatory myopathies, signified by distinctive peripheral cytokines, chemokines and the TNF family members B-cell activating factor and a proliferation inducing ligand.
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.
Szodoray
Peter
P
Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway. szodoray@gmail.com
Alex
Philip
P
Knowlton
Nicholas
N
Centola
Michael
M
Dozmorov
Igor
I
Csipo
Istvan
I
Nagy
Annamaria T
AT
Constantin
Tamas
T
Ponyi
Andrea
A
Nakken
Britt
B
Danko
Katalin
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D053264:B-Cell Activating Factor / Q000276:immunology*; D018925:Chemokines / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D018448:Models, Immunological; D009220:Myositis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha; D044465:White People; D055815:Young Adult
D053264:B-Cell Activating Factor; D018925:Chemokines; D016207:Cytokines; D008024:Ligands; D014409:Tumor Necrosis Factor-alpha