title: Anti-Interferon-Inducible Protein 16 Antibodies Associate With Digital Gangrene in Patients With Scleroderma.
abstract: To examine the association between anti-interferon-inducible protein 16 (anti-IFI-16) antibodies and clinical features of scleroderma.
  
  
  
  Sera from a discovery sample of 94 patients with scleroderma and 47 healthy controls were assayed for anti-IFI-16 antibodies by enzyme-linked immunosorbent assay, and associations were examined using regression analyses. Since anti-IFI-16 autoantibodies were found to be strongly associated with digital gangrene in the discovery sample, a subsequent case-control study (with subjects matched 1:1 on disease duration) was designed for further exploration. Cases were patients with scleroderma and digital gangrene, while controls were patients with scleroderma and Raynaud's phenomenon alone (n = 39 matched pairs). Nonparametric, unadjusted matched pairs analysis as well as univariate and multivariable conditional logistic regression analyses were performed.
  
  
  
  In the discovery sample, anti-IFI-16 antibodies were more prevalent in patients with scleroderma than in healthy controls (18% versus 2%; P = 0.01). Patients with anti-IFI-16 antibodies, compared to anti-IFI-16 antibody-negative patients, were more likely to have limited scleroderma (77% versus 46%; P = 0.03), a longer disease duration (median 15.2 years [interquartile range 10.6-18.3] versus 6.0 years [interquartile range 3.4-13.8]; P < 0.01), digital gangrene (24% versus 4%; P = 0.02), and a low diffusing capacity for carbon monoxide (DLco) (P < 0.01). In the case-control study, 35 (45%) of 78 patients were anti-IFI-16 antibody positive. Anti-IFI-16 antibody levels were significantly higher in cases with digital gangrene than in matched controls (P = 0.02). In analyses adjusted for age, cutaneous scleroderma subtype, smoking, and DLco, high anti-IFI-16 antibody levels were associated with the presence of digital gangrene (adjusted odds ratio 2.3, 95% confidence interval 1.0-5.6, P = 0.05). The odds of having digital gangrene increased with higher anti-IFI-16 antibody titers, in a dose-dependent manner.
  
  
  
  Anti-IFI-16 antibodies are associated with digital gangrene in patients with scleroderma. Longitudinal prospective studies exploring anti-IFI-16 antibodies as a disease biomarker, and biologic studies investigating the pathogenicity of these antibodies, are warranted.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Zsuzsanna H
authors.initials: ZH
authors.lastname: McMahan
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ami A
authors.initials: AA
authors.lastname: Shah
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Vaidya
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Fredrick M
authors.initials: FM
authors.lastname: Wigley
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Antony
authors.initials: A
authors.lastname: Rosen
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Livia
authors.initials: L
authors.lastname: Casciola-Rosen
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005385:Fingers / Q000473:pathology*; D005734:Gangrene / Q000276:immunology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology*; D011928:Raynaud Disease / Q000276:immunology*; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D009687:Nuclear Proteins; D010750:Phosphoproteins; C076700:IFI16 protein, human