‘Epistatic interactions between autoimmunity and genetic thrombophilia’

In the recent article by Bakir-Gungor et al,¹ a novel method of analysis is proposed to elucidate the genetic pathways that are considered essential in the phenotypic expression of complex diseases, such as Behçet’s disease (BD). The combined analysis of the data of two genome-wide association studies (GWAS) that were conducted in the Turkish and Japan populations with BD^{2, 3} reveals a shared pathway between the complement and the coagulation cascade.

On the basis of the epidemiological data and the diagnostic assessment of three patients with major vessel thrombosis who were hospitalized in our department, we have previously formulated the medical hypothesis that the occurrence of genetic thrombophilia and certain features of the complex spectrum of BD in selected patients with thrombosis may not represent a coincidental coexistence, but rather the core features of a genetically based distinct nosological entity.⁴ The role of synergistic epistasis is considered the key in this hypothesis, which stems from the observation of three facts with respect to the thrombotic phenomena of BD.⁴ The first is that the prevalence of vascular thrombosis in BD is significantly higher in certain populations; the second is that the highest prevalence of certain inherited procoagulant factors are concomitant to the highest prevalence of vasculo-BD in specific ethnic populations; and the third and most important is that only certain reports in the literature confirm a positive association between specific inherited procoagulant factors and thrombotic manifestations in BD patients.

The theoretical background of this hypothesis seems to be supported in a preliminary stage through the scientific work of Bakir-Gungor et al,¹ and although its data cannot result in safe and comprehensive conclusions, we are strong advocates of similar future studies. Beside, there is now a body of evidence that imply the epistatic interaction between inherited thrombophilia and autoimmunity. In a recent experimental study by Katzav et al,⁵ it has been demonstrated that when heterozygous and homozygous factor V-Leiden transgenic mice were immunized with antiphospholipid antibodies there have been various autoimmune responses resulting in neurodegenerative manifestations. Further research in the field of GWAS with the methodology presented by Bakir-Gungor et al.¹ seems to be the future direction to elucidate the pathways in complex diseases and therefore individualize the treatments or even re-evaluate the classification of certain diseases.