The pathogenesis of neonatal autoimmune and autoinflammatory diseases: a comprehensive review

Abstract

Autoimmune and autoinflammatory diseases are two distinct disease entities that can present in the neonate. Autoimmune diseases of the newborn primarily include neonatal lupus and neonatal anti-phospholipid syndrome, but other diseases have been reported as well. The pathogenic mechanisms behind autoimmune diseases of the newborns are unknown, but an association with antibodies to Ro and La is present in most cases. The extent to which these antibodies play a pathogenic role is unknown. Because the phenotype of clinical neonatal lupus is variable in many mothers who possess the antibodies, other mechanisms may be necessary to confer disease. The primary theories include apoptosis of cardiac cells, maternal microchimerism, cross-reactivity of the autoantibodies with cardiac tissue, T cell dysregulation and inhibitory receptors, and a genetic predisposition. The autoinflammatory diseases are unrelated to neonatal autoimmune diseases and include the cryopyrin-associated periodic syndromes (CAPS). These diseases include familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome and neonatal onset multisystem inflammatory disease (NOMID). All of these diseases share a defect in a common gene--the CIAS1 or NALP3 gene on chromosome 1. The diseases vary in severity and involvement of different physiologic systems, with FCAS being the mildest form and NOMID being the most severe form with involvement of the neurologic and hematologic systems. Aberrant functioning of the inflammasome may play a role in the pathogenesis of autoinflammatory diseases.