Anti-Interferon-Inducible Protein 16 Antibodies Associate with Digital Gangrene in Patients with Scleroderma

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Abstract

Objective To examine the association between anti-interferon-inducible protein 16 (anti-IFI-16) antibodies and clinical features of scleroderma. Methods 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. Results 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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)1262-1271
Number of pages10
JournalArthritis and Rheumatology
Volume68
Issue number5
DOIs
StatePublished - May 1 2016

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Gangrene
Interferons
Antibodies
Proteins
Case-Control Studies
Limited Scleroderma
Regression Analysis
Matched-Pair Analysis
Raynaud Disease
Carbon Monoxide
Autoantibodies
Longitudinal Studies
Virulence
Biomarkers
Logistic Models
Smoking
Enzyme-Linked Immunosorbent Assay
Odds Ratio

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology

Cite this

@article{0370698ea728425cb564829e1991aca2,
title = "Anti-Interferon-Inducible Protein 16 Antibodies Associate with Digital Gangrene in Patients with Scleroderma",
abstract = "Objective To examine the association between anti-interferon-inducible protein 16 (anti-IFI-16) antibodies and clinical features of scleroderma. Methods 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. Results 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. Conclusion 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.",
author = "Zsuzsanna McMahan and Ami Shah and Dhananjay Vaidya and Fredrick Wigley and Antony Rosen and {Casciola Rosen}, {Livia A}",
year = "2016",
month = "5",
day = "1",
doi = "10.1002/art.39558",
language = "English (US)",
volume = "68",
pages = "1262--1271",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "5",

}

TY - JOUR

T1 - Anti-Interferon-Inducible Protein 16 Antibodies Associate with Digital Gangrene in Patients with Scleroderma

AU - McMahan, Zsuzsanna

AU - Shah, Ami

AU - Vaidya, Dhananjay

AU - Wigley, Fredrick

AU - Rosen, Antony

AU - Casciola Rosen, Livia A

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Objective To examine the association between anti-interferon-inducible protein 16 (anti-IFI-16) antibodies and clinical features of scleroderma. Methods 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. Results 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. Conclusion 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.

AB - Objective To examine the association between anti-interferon-inducible protein 16 (anti-IFI-16) antibodies and clinical features of scleroderma. Methods 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. Results 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. Conclusion 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.

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