IgG4, complement, and the mechanisms of blister formation in pemphigus and bullous pemphigoid

Autoimmune bullous diseases are at the forefront of the research field on autoimmune diseases. Pemphigus and pemphigoid were historical entities in the world of descriptive dermatology for a long time. Recently, however, dermatologists and skin biologists have elegantly explained the novel pathomechanism of pemphigus and pemphigoid diseases. IgG4 is the major subclass of autoantibodies in autoimmune bullous diseases and is known to have little activity to activate complement. It is quite acceptable for pemphigus, because acantholysis in pemphigus has been demonstrated to be complement-independent. On the other hand, subepidermal blister formation in bullous pemphigoid has been believed to be complement-dependent. Therefore, the role of IgG4 autoantibodies on blister formation in bullous pemphigoid remains controversial. Here, we examine the progress of research on the mechanisms of blister formation in autoimmune bullous diseases. We focus on the complement dependent and independent blistering in bullous pemphigoid using comparisons between pemphigus diseases. In addition, we review the current understanding of the role of IgG4 antibodies in bullous pemphigoid. (C) 2017 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.