Circulating Interferon‐Inducible Protein IFI16 Correlates With Clinical and Serological Features in Rheumatoid Arthritis

Abstract

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-CCPpositive 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.

Serum IFI16 and anti-IFI16 antibodies in psoriatic arthritis

“…The inflammatory context in which an intracellular protein is released is thought to be one of the mechanisms leading to the breakdown of tolerance and the recognition of self‐antigens; this hypothesis could explain the antibody response against IFI16 observed in PsA and Pso, particularly with the intriguing observation of a prevalent IgA response compared to IgG response in PsO versus PsA. As previously mentioned, and different from PsA (with anti‐IFI16 IgG titres slightly increased in subjects with elevated CRP levels), anti‐IFI16 antibodies are not correlated to RA activity, but rather with serum autoantibody positivity, while no association between anti‐IFI16 and disease activity or erosions has been found . In SLE, anti‐IFI16 antibodies were first reported to be associated with anti‐double‐stranded DNA antibodies , but this was not confirmed by our group .…”

Association between anti-citrullinated alpha enolase antibodies and clinical features in a cohort of patients with rheumatoid arthritis: a pilot study

“…Furthermore, smoking is strongly associated with the development of ILD. Therefore, smokers are more likely to be seropositive and more often develop RA-ILD (23,24). However, it is conceivable that other mechanisms could be responsible for aberrant peptide citrullination, otherwise the presence of ACPA in non-smokers could not be explained.…”

Relevance of Interferon‐Inducible Protein‐16 Rather than Anti–Interferon‐Inducible Protein‐16 Autoantibodies as a Clinical and Pathogenic Biomarker in Primary Sjögren's Syndrome: Comment on the Article by Baer et al

“…Some studies, in fact, suggested a protective rather than proinflammatory role of anti-IFI16 autoantibodies (8,9). On the contrary, there is consistent evidence for a pathogenic role of IFI16 protein in triggering and perpetuating inflammation in some chronic inflammatory and autoimmune rheumatic disorders (10).…”