Correlation of Serum Levels of IgE Autoantibodies Against BP180 With Bullous Pemphigoid Disease Activity | Dermatology | JAMA Dermatology | JAMA Network
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Original Investigation
January 2017

Correlation of Serum Levels of IgE Autoantibodies Against BP180 With Bullous Pemphigoid Disease Activity

Author Affiliations
  • 1Department of Dermatology, University of Lübeck, Lübeck, Germany
  • 2Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany
JAMA Dermatol. 2017;153(1):30-38. doi:10.1001/jamadermatol.2016.3357
Key Points

Question  In bullous pemphigoid (BP), are serum levels of IgE autoantibodies against BP180 NC16A correlated with the disease activity or associated with the urticarial phenotype?

Findings  In this noninterventional study, anti-BP180 NC16A serum IgE was found in 47 of 117 (40.2%) BP cases, which paralleled disease activity but showed no association with urticarial or erythematous lesions. In contrast, the presence of anti-BP180 NC16A IgG was associated with the presence of erosions and blisters.

Meaning  Anti-BP180 NC16A IgE appears to be of pathogenic significance, although its exact pathogenic role remains to be elucidated.


Importance  Bullous pemphigoid (BP) is by far the most frequent autoimmune blistering disease. The presence of IgE autoantibodies against the transmembrane protein BP antigen 2 (BP180, type XVII collagen) has previously been reported in 22% to 100% of BP serum samples, and the pathogenic relevance of anti-BP180 IgE has been suggested in various experimental models and by the successful use of omalizumab in individual patients with BP.

Objectives  To determine the rate of anti-BP180–reactive IgE in BP, to evaluate the diagnostic relevance of anti-BP180 IgE in BP, and to correlate anti-BP180 IgE with disease activity and the clinical phenotype of patients with BP.

Design, Setting, and Participants  This case-control cohort study examined 3 groups of patients with BP. Sixty-five patients with BP underwent an enzyme-linked immunosorbent assay for IgE antibodies against the 16th noncollagenous domain of BP180 (NC16A); 52 consecutive patients with BP underwent clinical evaluation with the Bullous Pemphigoid Disease Activity Index (BPDAI); and 36 patients with BP without anti-BP180 NC16A IgG reactivity underwent evaluation of the diagnostic importance of serum anti-BP180 IgE. In addition, 49 age-matched control individuals with noninflammatory dermatoses, 127 controls undergoing allergy testing for IgE levels, and 30 controls with pemphigus vulgaris or pemphigus foliaceus were included for comparison. Patients were seen at a university clinic from January 1, 2008, to July 31, 2014.

Main Outcomes and Measures  Serum anti-BP180 NC16A IgE and IgG levels and BPDAI scores.

Results  Of 117 patients with BP (69 women and 48 men), anti-BP180 NC16A serum IgE was detected in 47 (40.2%) and correlated with disease activity as measured by total BPDAI (r = 0.918; P = .06). An intraindividual correlation of anti-BP180 NC16A serum levels with the total BPDAI was observed during the course of the disease in 10 randomly selected patients with BP (r = 0.983; P = .003). Although no association of circulating BP180 NC16A IgE antibodies with urticarial or erythematous lesions was observed (r = 0.481; P = .31), the presence of IgG anti-BP180 NC16A antibodies was associated with the occurrence of erosions and blisters (r = 0.985; P = .006) but not urticarial and erythematous lesions (r = 0.632; P = .23). Assaying for anti-BP180 IgE increased the diagnostic sensitivity by only 2.2% (1 of 46 serum samples) when combined with the IgG anti-BP180 enzyme-linked immunosorbent assay.

Conclusions and Relevance  Although detection of serum anti-BP180 IgE is not of diagnostic importance, it may be relevant for therapeutic decisions (eg, the use of anti-IgE treatment). The correlation of serum anti-BP180 NC16A IgE levels with disease activity in patients with BP supports the notion that anti-BP180 IgE is of pathogenic relevance. Our observation that IgG anti-BP180 antibodies are related to the occurrence of blisters and erosions may encourage further studies on the association of fine autoantibody reactivities with clinical features of BP.