Autoantibodies to the extracellular and intracellular domain of bullous pemphigoid 180, the putative key autoantigen in bullous pemphigoid, belong predominantly to the TgG1 and IgG4 subclasses

Background Autoantibodies to the extracellular domain (ECD) of bullous pemp higoid (BP) antigen 180 (BP180) are thought to play a crucial part in the p athophysiology of BP. Objectives As the various IgG subclasses have different biological properti es, we have sought to assess the relative isotype distribution of IgG to BP 180 and their reactivity against the ECD and intracellular domain (ICD) of BP180. Methods The reactivity of 27 sera from patients with BP was assayed by immu noblotting against recombinant proteins covering the ECD and ICD of BP180, Results Twenty-seven (100%) and 21 (77%) of 27 BP sera, respectively, conta ined IgG1 and IgG4 autoantibodies binding to the ECD of BP180. Fourteen (82 %) and six (35%) of the 17 BP sera that were reactive with the ICD of BP180 had autoantibodies of the IgG1 and IgG4 subclass, respectively The profile of the isotype restriction appeared to be similar when the response to the ECD vs, that to the ICD was compared. IgG2 and IgG3 reactivity with BP180 was found less frequently. Patients with BP of longer duration showed a ten dency to have, in addition to IgG1, an IgG4 response. Conclusions Consistent with prior evidence indicating that subepidermal bli ster formation in BP is dependent upon complement activation, the frequent finding of complement-fixing IgG1 autoantibodies to bath the ECD and ICD of BP180 might have pathogenic relevance in BP. These findings provide new in sights relevant for our understanding of the immune response to BP180, the putative key autoantigen in BP.