Interferons and innate immune activation in autoimmune congenital heart block

Abstract

Autoimmune congenital heart block (CHB) may develop in foetuses of women carrying anti-Ro/SSA and La/SSB autoantibodies and is characterized by disruption of signal conduction at the atrioventricular (AV) node, resulting in partial or complete AV block. If not fatal in utero, complete CHB typically requires lifelong cardiac pacing. No treatment has so far been unequivocally demonstrated to prevent or treat autoimmune CHB, and the relatively low incidence (1%-5%) and recurrence (12%-16%) rates of second/third-degree AV block add to the complexity of managing pregnancies in women with anti-Ro/La antibodies. Altogether, a better understanding of events leading to development of autoimmune CHB is needed to improve surveillance and treatment strategies. In the past decade, studies have started to look beyond the role of maternal autoantibodies in disease pathogenesis to assess other contributing factors such as foetal genetics and, more recently, immune responses in foetuses and neonates of anti-Ro/La antibody-positive women. In this review, we provide an update on the epidemiology, clinical presentation and current treatment approaches of autoimmune CHB, summarize the previously proposed pathogenic mechanisms implicating maternal autoantibodies, and discuss the recent findings of type I interferon (IFN) and innate immune activation in foetuses with autoimmune CHB and in neonates of anti-Ro/La antibody-positive mothers, and how these may contribute to autoimmune CHB pathogenesis.

Neutrophil Count as Atrioventricular Block (AVB) Predictor following Pediatric Heart Surgery

“…In autoimmune AVB, some authors described the role of maternal autoantibodies (anti-Ro, anti-La) in triggering cascade that destroys the atrioventricular node [ 25 ]. The immunological activation after heart surgery was reported in autoimmune Miller Fisher syndrome [ 26 ].…”

Interferons and interferon-related pathways in heart disease

“…The monogenic type I interferonopathy Aicardi-Goutières syndrome ( 39 ) may present with an inflammatory cardiomyopathy ( 40 ); and type I IFNs have also been implicated in the pathogenesis of autoimmune congenital heart block ( 41 ). That being said, cardiac disease is not always a feature of interferonopathy.…”