The circulating interferon-inducible protein IFI16 correlates with clinical and serological features in rheumatoid arthritis

OBJECTIVE: The IFN-inducible protein 16 (IFI16) has been detected in sera from patients with autoimmune/inflammatory diseases but not in healthy subjects. This leaking leads to loss of tolerance towards this self-protein and the development of autoantibodies. In this study, clinical significance of both IFI16 protein and anti-IFI16 antibodies (Abs) in rheumatoid arthritis (RA) was investigated. METHODS: IFI16 protein and anti-IFI16 Abs levels were assessed by ELISA in serum samples from 154 RA patients and 182 healthy controls (HC), and in synovial fluid (SF) samples from 21 RA patients and 25 patients with osteoarthritis (OA). RESULTS: Mean serum levels for both IFI16 and anti-IFI16 Abs were higher in RA than in HC with a direct correlation between IFI16 concentration and anti-IFI16 Abs titer. The majority of RA patients with detectable circulating IFI16 protein were also positive for RF/ACPA. The latter group was found positive for anti-IFI16 Abs as well. The mean SF concentrations of both IFI16 protein and anti-IFI16 Abs were higher in RA when compared with control OA. Interestingly, the presence of circulating IFI16 protein, but not anti-IFI16 Abs, significantly correlated with RA-associated pulmonary disease. This correlation was not dependent on the presence of anti-IFI16 Abs, gender and smoking habit. CONCLUSION: Our data demonstrate that the high levels of circulating IFI16 in RA are more frequent in RF/ACPA-positive RA patients and significantly associated with pulmonary involvement. The relevance of circulating IFI16 protein as new clinical biomarker of RA should be verified with additional studies.