What is the origin of antiphospholipid antibodies?

Abstract

Antiphospholipid antibodies (aPLs) are associated with the recurrent pregnancy loss and thrombosis that characterizes the antiphospholipid antibody syndrome. Although the ontogeny of these pathogenic antibodies has not been fully elucidated, there is evidence that indicates the involvement of both genetic and environmental factors. The evidence for the influence of HLA- and non-HLA-associated genes on the development of aPL and on the expression of disease has been garnered from animal genetic studies and human family and population studies. Several in vitro and in vivo animal studies have demonstrated the important role played by several environmental factors, in particular infectious agents, in the production of pathogenic aPL. Infectious agents can potentially induce autoimmune responses by molecular mimicry, selectively activating or destroying unique lymphocyte subsets, directing cytokine/chemokine release, or exposing cryptic autoantigens during cell necrosis and/or apoptosis. This chapter reviews the most up-to-date scientific evidence relating to the contributions of genetic and environmental factors to the development of pathogenic aPL.