Association of serum interferon alpha-2a levels with disease severity and prognosis in systemic sclerosis.

OBJECTIVE

To determine serum type I IFN (IFN-α2a) concentrations in SSc patients, explore its association with cytokine/chemokine expressions and evaluate correlation with the phenotype including the predictive value for interstitial lung disease (ILD) progression.

METHODS

Serum samples were obtained from 200 SSc patients and 29 healthy controls. IFN-α2a levels were measured by ultrasensitive electrochemiluminescence assay. Pro-inflammatory and chemokine panels were determined by Luminex® Discovery Assay multiplex kit. Baseline SSc disease characteristics were recorded together with longitudinal data for determining ILD progression after 2 years.

RESULTS

IFN-α2a concentrations were higher in SSc patients compared with controls, although not reaching significance [means ± SD of 49.20 ± 156.8 fg/ml vs 9.606 ± 4.399 fg/ml, respectively (P = 0.158)]. Using the cut-off of 15.9 fg/ml, we identified 62 patients as having a type 1 (T1) IFN signature in their circulation. Patients with an IFN signature had significantly higher levels of chemokines (CCL8, CCL19, CXCL10, CXCL11) and the cytokine IL-1α compared with those without an IFN signature. IFN-α2a concentrations strongly correlated with a T1 IFN-related chemokine score supporting activation of this pathway. Phenotyping association queries revealed association between IFN values and both skin and ILD involvements at baseline. Longitudinal data did not identify IFN as a predictive marker for ILD progression.

CONCLUSION

Using serum determinations, the activation of the T1 IFN pathway showed strong correlations with inflammatory mediators and associations with clinical manifestations, especially skin fibrosis and ILD in SSc patients. However, activated IFN pathway was not predictive of ILD progression.