Objective The interferon-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 toward this self-protein and the development of autoantibodies. In this study, clinical significance of both IFI16 protein and anti-IFI16 antibodies in rheumatoid arthritis (RA) was investigated. Methods IFI16 protein and anti-IFI16 antibody levels were assessed by enzyme-linked immunosorbent assay in serum samples from 154 RA patients and 182 healthy controls, 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 antibodies were higher in RA patients than in healthy controls, with a direct correlation between IFI16 concentration and anti-IFI16 antibody titer. The majority of RA patients with detectable circulating IFI16 protein were also positive for rheumatoid factor (RF)/anti-cyclic citrullinated peptide antibody (anti-CCP). The latter group was found to be positive for anti-IFI16 antibodies as well. The mean SF concentrations of both IFI16 protein and anti-IFI16 antibodies were higher in RA patients when compared with control OA patients. Interestingly, the presence of circulating IFI16 protein, but not anti-IFI16 antibodies, significantly correlated with RA-associated pulmonary disease. This correlation was not dependent on the presence of anti-IFI16 antibodies, sex, and smoking habit. Conclusion Our data demonstrate that the high levels of circulating IFI16 in RA are more frequent in RF/anti-CCP-positive RA patients and significantly associated with pulmonary involvement. The relevance of circulating IFI16 protein as a new clinical biomarker of RA should be verified with additional studies.
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