Biomarkers Predict Digital Vascular Events in Scleroderma

The likelihood of digital vascular pits, ulcers, or gangrene is increased in patients with scleroderma who are double-positive for anti-interferon-inducible protein 16 and anticentromere autoantibodies.

Particularly high anti-interferon-inducible protein 16 levels were found in patients with scleroderma who had active ischemic ulcers or gangrene.

Measuring anti-interferon-inducible protein 16 levels in patients with scleroderma and anticentromere antibody positivity may help stratify those at high risk for significant digital vascular events.

Early intervention could improve outcomes in patients with scleroderma, making risk stratification important. Zsuzsanna McMahan and colleagues at Johns Hopkins University suggest that early aggressive treatment of progressive vascular disease in patients with scleroderma could help prevent peripheral vascular complications.

“Identifying the patients who are at the highest risk of serious vascular complications is important but clinically challenging,” they said.

Patients with scleroderma who are positive for anticentromere antibodies are known to be at higher risk for vascular complications. But it is not known whether double positivity with anti-interferon-inducible protein 16 confers even greater risk.

The authors presented the findings of their study examining double positivity with anticentromere antibodies and anti-interferon-inducible protein 16 as biomarkers for increased vascular events in patients with scleroderma in a recent Arthritis Care & Research article.

The study

The authors conducted a retrospective cross-sectional study that included 165 patients with scleroderma who were anticentromere antibody positive.

Specifically, 2 groups were compared, those with both anticentromere antibodies and anti-interferon-inducible protein 16 and those with only anticentromere antibodies.

The results

• Of the 165 patients with scleroderma and anticentromere antibodies, 12.7% also were positive for anti-interferon-inducible protein 16.

• 42 patients had digital pits, 39 had digital ulcers, and 15 had digital gangrene.

• Of the 21 (12.7%) subjects who were double-positive for anti-interferon-inducible protein 16 and anti-centromere antibodies, 85.7% were women, 90% were Caucasian, 10% were African American, and 90.5% had the limited cutaneous subtype of scleroderma.

• The presence of calcinosis, a condition related to vascular hypoxia, was higher, although not significantly, in the double-positive group (71% versus 56%; P=0.17).

• Digital pits, ulcers, and gangrene were significantly more common in patients with double-positive antibody status when compared with those who had only anticentromere antibody positivity (81% versus 56%; P=0.03).

• The loss of a digit was more common in the double-positive antibody group (29% versus 17%; P=0.19).

• Higher levels of anti-interferon-inducible protein 16 were significantly associated with digital loss (odds ratio, 2.67, 95% confidence interval, 1.15-6.22; P=0.01).

• After all adjustments, double-positive patients remained at higher risk for significant digital vascular events when compared with patients who had only anticentromere antibody positivity (odds ratio, 3.55, 95% confidence interval, 1.1-11.3: P=0.03).

Implications for physicians

• Patients with positivity for both anticentromere antibodies and anti-interferon-inducible protein 16 are at 3.5 times higher risk for clinically significant digital vascular events than those who have only anticentromere antibody positivity.

• Combining the anticentromere antibody and anti-interferon-inducible protein 16 assays in patients with scleroderma may identify patients at higher risk for digital vascular events and lead to earlier treatment.

• High levels of anti-interferon-inducible protein 16 in patients with scleroderma who have anticentromere antibody positivity are associated with loss of digits.

Disclosures:

The Rheumatology Research Foundation Scientist Development Award, the Jerome L. Greene Foundation, the Scleroderma Research Foundation, the Marth McCrory Professorship, and the NIH supplied funding for this project.

References:

Zsuzsanna H. McMahan, Frederick M. Wigley, and Livia Casciola-Rosen. “Risk of digital vascular events in scleroderma patients who have both anticentromere and anti–interferon-inducible protein 16 antibodies.” Arthritis Care Res (Hoboken). 2017;69:922-926. doi: 10.1002/acr.22978.