THE EXPANDING POTENTIAL OF GROWTH DIFFERENTIATION FACTOR-15 AS A BIOMARKER: CAN THE CYTOKINE AID TO IDENTIFY MYOSITIS OF AUTOIMMUNE ORIGIN?
- Boel De Paepe, Belgium
Abstract
Background and Aims
Distinguishing autoimmune myositis from other muscle disorders with prominent intramuscular inflammation such as muscular dystrophies, is often not easy yet highly relevant for guiding therapeutic decisions and for offering founded prognoses. We investigated the biomarker potential of growth differentiation factor-15 (GDF-15), a cytokine associated with inflammation, to differentiate myositis of autoimmune origin.
Methods
Sera from 35 myositis patients were collected, who had been diagnosed with immune-mediated necrotizing myopathy (n=21), sporadic inclusion body myositis (n=10), polymyositis (n=3), and dermatomyositis (n=1). GDF-15 protein levels were determined using a commercial enzyme-linked immunosorbent assay, and compared with the levels in sera from healthy controls (n=10), and patients with limb girdle muscular dystrophy or mitochondrial myopathies (n=8). Muscle tissue GDF-15 expression patterns were studied using double immunofluorescent staining.
Results
Serum levels of GDF-15 were significantly higher in myositis patients (625±358 pg/ml) than in healthy controls (326±204 pg/ml) (Mann-Whitney U test p=0.01), with no difference between patient subgroups (p=0.1). No correlation was found between GDF-15 levels and blood CK values (p=0.2). Patients with dystrophies displayed substantially lower levels (127±41 pg/ml), while patients with mitochondrial disease displayed the highest mean levels (1312±1393 pg/ml). GDF-15 could be localized to skeletal muscle fibers, with strong sarcoplasmic staining observed in subsets of small CD56 positive regenerating or denervated fibers, and in the inclusions present in sporadic inclusion body myositis fibers.
Conclusions
GDF-15 serum levels could represent a potential biomarker for myositis, with expression by skeletal muscle fibers being a probable source of the cytokine.