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Circulating Reticulocalbin 1 and Reticulocalbin 3 in Systemic Sclerosis Patients: Results of a Case Control Study
Insights
Serum levels of reticulocalbin 1 (RCN1) and reticulocalbin 3 (RCN3) were not significantly different in systemic sclerosis (Ssc) patients versus controls. However, RCN1 correlated with Ssc disease activity and may stratify patients with specific clinical features.
Area of Science:
- Rheumatology
- Proteomics
- Biomarker Discovery
Background:
- Systemic sclerosis (Ssc) requires validated biomarkers for patient management.
- Previous studies indicated elevated reticulocalbin 1 (RCN1) and reticulocalbin 3 (RCN3) in Ssc dermal fibroblasts.
- Circulating RCN1 and RCN3 require evaluation as potential Ssc biomarkers.
Purpose of the Study:
- To assess circulating RCN1 and RCN3 levels in systemic sclerosis (Ssc).
- To determine if RCN1 and RCN3 can serve as biomarkers for Ssc clinical expression.
Main Methods:
- Serum samples from 40 Ssc patients and 20 healthy controls were analyzed.
- Commercial ELISA kits were used to quantify RCN1 and RCN3 levels.
Main Results:
- No significant difference in serum RCN1 or RCN3 between Ssc patients and controls.
- Serum RCN1 and RCN3 showed significant correlation in both groups.
- Serum RCN1 positively correlated with Ssc disease activity (EUSTAR score) and remained significant after multivariate analysis.
- Elevated RCN1 in 15% of Ssc patients was associated with digital ulcers, higher disease activity, and specific Ssc subtypes.
Conclusions:
- Circulating RCN1 and RCN3 levels do not differ significantly between Ssc patients and healthy individuals.
- RCN1 shows association with disease activity score (EUSTAR), suggesting its potential as a stratification biomarker.
- High RCN1 levels may indicate a distinct clinical pattern in Ssc patients, aiding in patient stratification.
Background:
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.
Methods:
40 consecutive Ssc patients and 20 gender and age matched controls were included. Serum RCN1 and RCN3 was evaluated using commercial ELISA kits.
Results:
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.
Conclusions:
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.

