Toll interacting protein (TOLLIP) serum concentration in patients with systemic sclerosis (SSc), with and without...

Single nucleotide polymorphisms (SNPs) within Toll interacting protein (TOLLIP) coding gene have been associated with progression, prognosis and treatment response in idiopathic pulmonary fibrosis (IPF). These SNPs seem to influence mRNA expression and serum levels of TOLLIP. The aim of this study was to investigate TOLLIP serum concentrations in a previously genotyped cohort of patients with systemic sclerosis (SSc) with and without interstitial lung disease (ILD).

106 consecutive patients with SSc (77 female) with (n=53) and without ILD (n=53) and 60 healthy controls (HCs) were included. TOLLIP concentrations were measured using a commercially available ELISA kit (Cloud-Clone, USA) in serum samples from patients and HC previously genotyped for two SNPs within TOLLIP (rs3750920, rs5743890).

Patients with SSc had tendentially lower TOLLIP serum concentrations than HC (0.111 (95% CI 0.101 to 0.123) vs 0.141 (95% CI 0.104 to 0.191) ng/µL, p=0.076). Patients with SSc-ILD showed significantly higher TOLLIP levels than patients with SSc without ILD (0.126 (95% CI 0.106 to 0.151) vs 0.098 (95% CI 0.091 to 0.105) ng/µL, p=0.010). At a cut-off value of ≥0.1135 ng/µL serum TOLLIP yielded a 71% sensitivity and 74% specificity for identifying ILD (AUC=0.74, 95% CI 0.593 to 0.889, p=0.007). Serum TOLLIP concentrations did not differ significantly across rs3750920 or rs5743890 genotypes. TOLLIP concentration inversely correlated with age (r=-0.256, p<0.001), whereas no significant associations with gender, body mass index, C-reactive protein, forced vital capacity or diffusing capacity of the lung for carbon monoxide at time of sampling were observed.

Patients with SSc show lower TOLLIP serum concentrations than HC, while patients with SSc-ILD exhibit higher TOLLIP levels than those without. TOLLIP might serve as a biomarker of ILD in patients with SSc.