Clinical significance of serum growth differentiation factor-15 levels in systemic sclerosis: association with disease severity

Abstract

To determine serum growth differentiation factor-15 (GDF-15) levels and their clinical associations in patients with systemic sclerosis (SSc). Serum GDF-15 levels were examined by enzyme-linked immunosorbent assay in 61 patients with SSc and 24 healthy individuals. In a retrospective longitudinal study, sera from 14 patients with SSc were analyzed (duration of follow-up 1.2-7.2 years). Serum GDF-15 levels were significantly elevated in SSc patients (1340 ± 910 pg/ml) compared with healthy individuals (213 ± 79 pg/ml; P < 0.001). Among SSc patients, patients with diffuse cutaneous SSc (n = 31) had higher levels of serum GDF-15 (1609 ± 1069 pg/ml) than those with limited cutaneous SSc (n = 30; 1142 ± 646 pg/ml; P < 0.05). SSc patients with high GDF-15 levels (≥1000 pg/ml) had pulmonary fibrosis, decreased vital capacity, and decreased diffusion capacity for carbon monoxide more often than those with low GDF-15 levels (<1000 pg/ml). GDF-15 levels correlated positively with the extent of skin sclerosis and inversely with percentage vital capacity and diffusion capacity for carbon monoxide in patients with SSc. In a longitudinal study, serum GDF-15 levels were generally decreased during the follow-up. Serum GDF-15 levels were increased in patients with SSc and associated with the extent of skin sclerosis and the severity of pulmonary fibrosis. These results suggest that GDF-15 may play a role in the development of cutaneous and pulmonary fibrosis in SSc. Measurement of serum GDF-15 may be useful for risk stratification in early disease stage.