Pemphigoid gestationis: Toward a better understanding of the etiopathogenesis

Pemphigoid gestationis (PG) is the only autoimmune disease exclusively emerging in pregnancy. It belongs to the pemphigoid group of disorders, a class of autoimmune blistering skin diseases featuring an immune response against different hemidesmosomal proteins. PG is caused by a break of immunotolerance against the hemidesmosomal protein BP180. Several lines of evidence suggest that this break of immunotolerance is linked to specific maternal major histocompatibility complex (MHC) class II gene variants and aberrant expression of MHC class II molecules in the placenta. The close time association of the emergence of PG with pregnancy and the obviously very short period required from the initial break of immunotolerance to the onset of skin inflammation set PG into a unique position among autoimmune diseases in view of the fact that, for other autoimmune diseases, the time and site of the break of immunotolerance are usually vastly elusive and the period of silent disease can only be speculated on. In this review we highlight the features of PG and summarize current knowledge about its pathogenesis. We believe that this disease offers the best opportunity to elucidate comprehensively all phases of the pathogenesis of an autoantibody-driven disease.