Circulating Reticulocalbin 1 and Reticulocalbin 3 in Systemic Sclerosis Patients: Results of a Case Control Study

Proteomic candidate biomarkers for systemic sclerosis (Ssc) useful for appropriate patient evaluation and follow-up were identified in mass-spectrometry studies; however, most of these biomarkers were not evaluated and confirmed on independent patient samples. Up-regulation of reticulocalbin 1 (RCN1) and reticulocalbin 3 (RCN3) in the dermal fibroblast secretome originating from Ssc patients was previously described. The aim of the study was to evaluate circulating RCN1 and RCN3 as candidate biomarkers for Ssc clinical expression.40 consecutive Ssc patients and 20 gender and age matched controls were included. Serum RCN1 and RCN3 was evaluated using commercial ELISA kits.Serum RCN1 and RCN3 were not statistically significant different between Ssc patients and healthy controls. Serum RCN1 and RCN3 were correlated in both Ssc and healthy control groups (p < 0.001). Serum RCN1 was positively correlated with Ssc disease activity score (EUSTAR, p = 0.02) and remained associated with EUSTAR after adjusting for disease duration in multivariate analysis. 6 Ssc patients (15%) had elevated RCN1 values compared to reference values obtained from healthy control samples. These patients had higher prevalence of digital ulcers, higher disease activity scores, and tended to have esophageal hypomotility, calcinosis, telangiectasia, and diffuse Ssc subtype.RCN1 and RCN3 expression was not statistically significantly different to healthy controls. However, RCN1 was associated with disease activity score and could be used as a stratification biomarker for Ssc patients, as patients with high RCN1 shared a particular disease pattern.