IFI16 Autoantibodies

IFI16 belongs to the interferon (IFN)-inducible HIN-200/Ifi-200 gene family, which encodes evolutionary related human (IFI16, IFIX, MNDA, and AIM2) and murine (Ifi202a, Ifi202b, Ifi203, Ifi204, Ifi205/D3, and Ifi206) nuclear phosphoproteins. To detect anti-IFI16 antibodies in the sera from patients affected by autoimmune disorders, a semiquantitative enzyme-linked immunosorbent assay (ELISA) was generated and characterized using a recombinant purified IFI16 protein as antigen. Anti-IFI16 titers above the 95^th percentile for control subjects were observed in more than 50% of systemic lupus erythematosus (SLE) patients, 30% of systemic sclerosis (SSc) patients, and 25% of Sjögren syndrome (SjS) patients versus 6% of healthy donors. Anti-IFI16 antibodies were detected in 30% of the SSc patients who tested negative for both anticentromere (ACA) and anti-topo I (anti-Scl 70) antibodies. In this subgroup of patients, anti-IFI16 were significantly associated with the limited cutaneous form of SSc with a sensitivity of 40% and a specificity of 81%. Moreover, analysis of the distribution of anti-RNAP II antibodies versus anti-IFI16 in the same SSc population showed that they were mutually exclusive. Finally, anti-IFI16 were also significantly associated with heart involvement. In SLE patients, the prevalence and titers of anti-IFI16 antibodies were significantly higher in patients without renal involvement than in patients with glomerulonephritis (63% and 24%, respectively). Anti-IFI16 antibodies inversely correlated with proteinuria at univariate analysis and with C3 hypocomplementemia at univariate and multivariate analysis, including SLEDAI and anti-double-stranded deoxyribonucleic acid (dsDNA) as measures of disease activity. Although further studies are needed to clarify the exact mechanisms of the function of anti-IFI16 antibodies, these antibodies may serve as a new biomarker to be used in the diagnosis and assessment of disease activity in patients with SSc or SLE, with or without renal involvement.