Background/Purpose: Antiphospholipid antibodies (aPL) have been found in patients with various autoimmune and rheumatic diseases, including systemic sclerosis (SSc). However, in the absence of clinical events classically associated with the antiphospholipid syndrome, their significance remains unclear. This study aimed to determine the prevalence of aPL in a cohort of SSc patients, and to assess their clinical associations. AL and VS have contributed equally to this work.

Methods: A total of 249 adult patients who fulfilled 2013 ACR/EULAR criteria for SSc were consecutively included between October 2014 and January 2016. Patients were tested for lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2glycoproteine I (anti-β2GpI) antibodies. Positive titer was defined as ≥ 10 UGPL/mL (aCL) or ≥ 10 UA/mL (anti-β2GpI). aPL positivity was defined if at least one of the three antibodies was positive. Clinical associations between aPL positivity and thrombosis event, obstetrics event, pulmonary arterial hypertension (PAH) and digital ulcer were studied using binomial logistic regressions. Adjustments were done (i) a priori for gender, age, SSc subtype and tobacco history, and (ii) for the characteristics that differed significantly between aPL positive and negative patients. Similar analyzes were performed considering the titers of aCL and anti-β2GpI rather than the aPL status. Because these variables had a majority of zero values, they were categorized, as follows: (i) 0, ≥1 and <5, ≥5 and ≤20 UGPL/mL for aCL, and (ii) 0, ≥1 and <5, ≥5 and <10, ≥10 and ≤100 UA/mL for anti-β2GpI.

Results: The 249 patients were predominantly female (82.3%), with limited cutaneous SSc (81.5%). One or more type of aPL was present in 16 patients leading to a prevalence of 6.4% (95% confidence interval (CI) [3.4-9.5]). aPL positivity was associated with venous thrombosis in univariate analysis (OR=3.91; 95%CI [0.98-13.53]; p=0.027); there was a trend towards an association in multivariate analysis (OR=3.24; 95%CI [0.87-10.9]; p=0.064). aPL positivity was associated with miscarriage in multivariate analysis (OR=4.31; 95%CI [1.09-16.33]; p=0.031). We did not find any association between aPL positivity and PAH or digital ulcer. Titers of aCL ≥5 UGPL/mL were associated with PAH (OR=6.35; 95%CI [1-41.1]; p=0.043) and venous thrombosis (OR=3.69; 95%CI [0.98-12.9]; p=0.043) in multivariate analysis. Titers of anti-β2GpI ≥10 UA/mL and miscarriage were associated (OR=5.25; 95%CI [1.04-27.1]; p=0.041).

Conclusion: This study found a prevalence of aPL in SSc of 6.4% (95%CI [3.4-9.5]) in a French cohort. aPL positivity was associated with venous thrombosis and miscarriage. These data provide additional insights into the vascular involvement of SSc.