LAUSR

Bullous pemphigoid (BP) is an organ-specific autoimmune disease of the skin, characterized and caused by autoantibodies targeting BP180 and/or BP230. In the ‘classical’ and name-giving variant, BP patients present with blisters on inflamed skin. Yet, blisters on otherwise healthy skin, urticarial or nodular skin lesions without blistering may be even more common than the ‘classical’ clinical presentation. Itch, which is often severe, is, however, a common clinical symptom in BP. In addition to the variable clinical presentation, the autoimmune response differs among BP patients: A little over 50% of the BP patients have autoantibodies against BP180 and BP230, while approximately 1/3rd react exclusively to BP180, and 4%– 5% to BP230 only. Based on these findings, and on experimental data, inflammation and blistering in BP has been thought to be mediated by BP180 autoantibodies only. However, the pathogenicity of anti-BP230 autoantibodies has recently been well documented. Given the wide spectrum of clinical presentation and a diverse autoantibody reactivity in BP, one may assume that the different autoantibody reactivity and/or different IgG subclasses are leading to this clinical variability. However, the impact of the different autoantibody reactivities on the clinical disease manifestation in BP patients had not been addressed systematically. Furthermore, while the IgG subclass reactivity of antiBP180 is well documented, no such data have been reported for BP230 autoantibodies. In this issue of the Journal, Dr. Zheng and colleagues elaborately addressed these knowledge gaps: They first contrasted the IgG subclass distribution and C3 deposition in perilesional skin of BP180-BP230 to BP230 BP patients. While total IgG, IgG2 and IgG4 were equally present, IgG1, IgG3 and C3 were more frequently deposited along the dermal–epidermal junction in BP180-BP230 BP patients. Since, IgG1 and IgG3, but not IgG2 and IgG4 autoantibodies, induce Fc gamma receptor-dependent pathogenicity in pemphigoid diseases, BP230-only BP patients would be expected to present with less inflammatory BP. Indeed, in the cohort described by Dr. Zheng and colleagues, the urticaria/erythema item of the bullous pemphigoid disease area index (BPDAI) is significantly higher in BP180-BP230 BP patients (30 8) compared to those with reactivity to BP230 only (9 4). Yet, as a limitation, this is based on a relatively small patient cohort. Should this highly interesting finding be confirmed in larger patient cohorts, this would have a significant impact on BP patient care: Specifically, in my opinion, these results will stimulate research towards a so far not welladdressed field in pemphigoid disease research: Classification of patients not only based on their clinical presentation, but also on the underlying pathogenic mechanism, such as autoantibody reactivity and/or autoantibody subtypes/subclasses. While all these patients should be still termed BP, the autoantibody profile should be added to the disease name. In addition, these insights may also be used for the selection of personalized treatments for individual patients. For example, BP230 BP patients may need less of a topical anti-inflammatory treatment (such as topical steroids), but would rather benefit from treatments that impair the generation of autoantibodies (such as rituximab). Thus, inclusion of immunological data (and in the future possibly also Omics data) will pave the way to personalized medicine in BP, which will hopefully address the so far unmet medical need for this disease.