Anti-DFS antibodies occur more commonly in patients following unprovoked venous thromboembolism.

Abstract

Introduction: It has been reported in a small group of patients that a significant percentage of patients with anti-DFS (dense fine speckled) antibodies has a history of idiopathic arterial or venous thrombosis and/or obstetric complications. To our knowledge there have been no larger studies regarding the prevalence of anti-DFS antibodies in provoked and unprovoked venous thromboembolism (VTE).

Aim of the study: We investigated how common anti-DFS70 antibodies occur in patients following VTE and which factors affect their occurrence in this disease.

Material and methods: We screened 287 consecutive adult patients, aged below 60 years, with documented VTE treated for at least 3 months, and 129 age-matched healthy controls. Patients with cancer, severe comorbidities, documented autoimmune diseases, including antiphospholipid syndrome were ineligible. The anti- -DFS70 antibodies were determined based on immunofluorescence on Hep-2 cells. The specific immunofluorescence pattern, characterized by dense fine speckles distributed the nucleus, observed at serum dilution equal to or greater than 1:100, was considered as positive and was confirmed using the semiquantitative ELISA-DFS that provided results as a ratio (RU/ml) with a cut-off of 1.

Results: There was no difference in the prevalence of anti-DFS70 antibodies in the VTE and control patients (n=12, 4.18% vs. n=6, 4.65%, p=0.68). Anti-DFS antibodies represented 9.16% of all positive ANA patterns (n=131) in VTE patients, which was a much lower proportion compared with 26.1% of all 23 positive ANA patterns in healthy subjects (p=0.031). The presence of anti-DFS antibodies did not correlate with demographic or clinical variables including time since last VTE event, type of anticoagulation and its quality. The prevalence of anti-DFS70 antibodies was higher in patients with ANA titer ≥1:320 compared to those with the titer < 1:320 (75% vs. 37%, p=0.01). Of importance, higher prevalence of anti-DFS antibodies was observed in patients with unprovoked VTE compared to those with provoked VTE (75% vs. 25%, p=0.01). Among the VTE patients with heritable thrombophilia, i.e. factor V Leiden or prothrombin G20210A mutations, 25.8% of subjects (n=8) had anti-DFS antibodies. Moreover, anti-DFS titer was associated with serum alpha and gamma globulin levels (r=0.47, p=0.027; and r=0.39, p=0.045, respectively), but not with inflammatory markers or D-dimer in VTE patients.

Conclusions: Anti-DFS antibodies are present in <5% of VTE patients and are associated with unprovoked VTE including that related to heritable thrombophilia. It might suggest that these antibodies are involved in the pathogenesis of idiopathic VTE.