Given the flood of attention directed toward understanding the affector arm in autoimmune diseases, studies that address the effector arm to study the pathogenicity of the perpetrator are of great interest. In certain circumstances the effects of an autoantibody may even be beneficial. This was in fact the situation being studied by Dieudé et al, who sought the mechanism by which autoantibodies to nuclear lamin B1 abrogate the strong prothrombotic risk associated with the lupus anticoagulant (1). The authors tested the hypothesis that circulating anti–lamin B1 antibodies block the procoagulant effect of apoptotic blebs by binding to lamin B1 displayed at the external surface of the blebs. However, by both biochemical and morphologic criteria, their extensive studies convincingly negated this notion. Lamin B1, in contrast to SSB/La, is not present on the surface of the apoptotic blebs but rather remains buried within the bleb, thereby being inaccessible to external anti–lamin B1 antibodies. Although these findings were considered negative in one context, they are indeed informative when considering another context.

As discussed by the authors, although apoptotic blebs serve as an important target for certain autoantibodies, it is now apparent that this is not generalizable to all autoantigens. With regard to the pathogenicity of anti-SSA/Ro and anti-SSB/La in the development of congenital heart block, unambiguous demonstration of antibody binding to the surface of apoptotic cardiomyocytes was a critical link that provided a plausible explanation of how antibodies were accessible to otherwise sequestered intracellular antigens (2). If intracellular trafficking of sequestered nuclear antigens to the membrane surface is not universally applicable to all such antigens, this may help explain the specificity of one antibody system versus another in the pathogenesis of disease, in particular tissue damage in the developing fetal heart.