Serum IFI16 and anti-IFI16 antibodies in psoriatic arthritis.

Nuclear interferon-inducible protein 16 (IFI16) and anti-IFI16 antibodies have been detected in subjects with several rheumatic diseases, often correlating with disease severity, and in this study we investigated their prevalence and clinical associations in psoriatic arthritis (PsA) compared to psoriasis (Pso). We tested sera and synovial fluids of patients with PsA for IFI16 protein levels by capture enzyme-linked immunosorbent assay (ELISA) and for anti-IFI16 immunoglobulin (Ig)G and IgA by ELISA, protein radio-immunoprecipitation and immunoprecipitation-Western blot of IgG. Sera from patients with Pso and healthy subjects were used as controls, and in a subgroup of patients with PsA we also studied sera after treatment with etanercept. IFI16 was detectable in the sera of 66% of patients with Pso, 46% with PsA and 19% of controls. Among PsA cases, 51% of IFI16-positive cases had elevated levels of C-reactive protein (CRP) compared to 31% of patients with undetectable IFI16. Anti-IFI16 of both IgG and IgA isoforms were detected with significantly higher frequency in PsA and Pso compared to healthy controls, with higher IgG titres in patients with elevated C-reactive protein (CRP) (P = 0·015). Immunoprecipitation confirmed the presence of anti-IFI16 IgG antibodies and these preferentially recognized epitopes outside the N-terminus of the protein. Lastly, IFI16 was detected in one of seven and anti-IFI16 in three of seven synovial fluids from patients with PsA. Therefore, IFI16 and anti-IFI16 are detectable in serum and synovial fluid of PsA patients, especially in cases of elevated CRP.

Interferon gamma-inducible protein 16 (IFI16) and anti-IFI16 antibodies in primary Sjögren's syndrome: findings in serum and minor salivary glands.

The interferon (IFN) signature, namely the overexpression of IFN-inducible genes is a crucial aspect in the pathogenesis of primary Sjögren's syndrome (pSS). The IFN-inducible IFI16 protein, normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders including pSS. This leads to tolerance breaking to this self-protein and development of anti-IFI16 antibodies. The aim of this study was to identify pathogenic and clinical significance of IFI16 and anti-IFI16 autoantibodies in pSS. IFI16 and anti-IFI16 were assessed in the serum of 30 pSS patients and one-hundred healthy donors (HD) by ELISA. IFI16 was also evaluated in 5 minor salivary glands (MSGs) of pSS patients and 5 MSGs of non-pSS patients with sicca symptoms by immunohistochemistry. Normal MSGs do not constitutively express IFI16. Conversely, in pSS-MSGs a marked expression and cytoplasmic mislocalization of IFI16 by epithelial cells was observed with infiltrations in lymphocytes and peri/ intra-lesional endothelium. pSS patients display higher serum levels of both IFI16 and anti-IFI16 autoantibodies compared to HD. Our data suggest that IFI16 protein may be involved in the initiation and perpetuation of glandular inflammation occurring in pSS.

Anti-IFI16 antibodies and their relation to disease characteristics in systemic lupus erythematosus.

OBJECTIVE: Several studies have shown the presence of anti-IFI16 antibodies in systemic lupus erythematosus (SLE), Sjögren Syndrome (SjS), systemic sclerosis (SSc) and other autoimmune diseases. However, the significance of anti-IFI16 antibodies in SLE has not been fully characterized. The aim of this study was to investigate associations between anti-IFI16 antibodies and clinical and serologic parameters of SLE. METHODS: An enzyme-linked immunosorbent assay (ELISA) kit was used to measure anti-IFI16 antibodies in the sera of 168 SLE patients, 46 patients with any type of primary glomerulonephritis (GN) and 182 healthy controls (HCs). Associations between anti-IFI16 antibodies and clinical and serologic parameters of SLE were statistically evaluated using both univariate and multivariate analysis. RESULTS: Significantly higher anti-IFI16 titres were observed in SLE patients compared to both non-SLE GN and HCs (median levels: 270.1 U/ml vs 132.1 U/ml, p = 0.001, and 52.9 U/ml, p < 0.0001, respectively). With cut-off levels corresponding to the 95th percentile of the control population (113 U/ml), 63% of the SLE patients tested positive for anti-IFI16 autoantibodies, compared to just 24% of patients with primary non-SLE GN and 5% of HCs. The presence of anti-IFI16 antibodies inversely correlated with proteinuria (univariate analysis) and C3 hypocomplementaemia (univariate and multivariate analyses). CONCLUSIONS: The inverse correlations observed between anti-IFI16 positivity, proteinuria and C3 hypocomplementaemia suggest that anti-IFI16 antibodies do not contribute to renal inflammation in SLE; indeed they may even prevent complement consumption. Anti-IFI16 antibodies hold the potential to serve as a new biomarker of disease activity in SLE.