Risk of Digital Vascular Events in Scleroderma Patients Who Have Both Anticentromere and Anti–Interferon-Inducible Protein 16 Antibodies

Objective: To evaluate whether scleroderma patients who are double-positive for anti–interferon-inducible protein 16 (anti–IFI-16) antibodies and anticentromere (anti-CENP) antibodies are at increased risk for significant digital vascular events relative to patients positive for anti-CENP antibodies alone. Methods: Sera from 165 scleroderma patients who tested positive for anti-CENP antibodies upon clinical evaluation were reassayed for both anti-CENP and anti–IFI-16 antibodies using enzyme-linked immunosorbent assay testing. Patients who were positive for anti-CENP antibodies alone were then compared to patients who were double-positive for both anti–IFI-16 and anti-CENP antibodies. The association between a history of significant digital vascular events (digital pits, ischemic digital ulcers, and/or gangrene) and double-positive antibody status was examined using chi-square tests. After completion of univariate analysis, multivariable analyses were done to adjust for clinically relevant covariates. Results: Of the 165 anti–CENP antibody positive patients, 21 (12.7%) also had anti–IFI-16 antibodies. Patients who were double-positive for anti-CENP and anti-IFI-16 antibodies were more likely to have had digital pits, ischemic digital ulcers, and/or gangrene (P = 0.03). After adjustment for clinically relevant covariates (age, cutaneous subtype, disease duration, and smoking), double-positive patients remained at significantly higher odds of having severe Raynaud's phenomenon (odds ratio 3.5 [95% confidence interval 1.1–11.1]; P = 0.03). Conclusion: Scleroderma patients who are double-positive for antibodies recognizing CENP and IFI-16 are significantly more likely to have significant digital vascular events during the course of their disease. This study provides further evidence that anti-CENP and anti–IFI-16 antibodies are disease biomarkers that may be used for risk stratification of vascular events in scleroderma.