Autoimmune Bullae-Forming Skin Disease Associated with IgE Autoantibodies

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Researchers have made an important discovery that may lead to new treatment for patients with bullous pemphigoid, a chronic autoimmune skin disease causing blisters.

A clear correlation between IgE anti-BP180 NC16A serum levels with disease activity suggests a pathogenic role of IgE autoantibodies in bullous pemphigoid, according to a case-control cohort study published in the current issue of JAMA Dermatology.

Beek et al. noted that bullous pemphigoid is easily the most common autoimmune blistering disease. IgE autoantibodies against the transmembrane protein bullous pemphigoid antigen 2 (BP180, type XVII collagen) have been reported in 22-100 percent of bullous pemphigoid serum samples. Various experimental models and the success of bullous pemphigoid treatment in individual patients with omalizumab, have suggested the pathogenic relevance of anti-BP180 IgE.

The study aim was to determine, with respect to anti-PB180 IgE, its rate in bullous pemphigoid, its diagnostic relevance, its correlation with disease activity and the clinical phenotype of bullous pemphigoid patients.

The non-interventional study evaluated a total of 153 sera obtained from three separate cohorts of patients with bullous pemphigoid by Ige ELISA using BP180 NC16a domain recombinant proteins. An additional 206 non-bullous pemphigoid dermatology patients were entered as controls. The outcome measures were serum anti-BP180 NC16A IgE and IgG levels and Bullous Pemphigoid Disease Activity Index (BPDAI).

Anti-BP180 NC16A serum IgE was detected in 47 (40.2%) out of 117 patients (69 women and 48 men) with bullous pemphigoid. The presence of anti-BP180 NC16A serum IgE correlated with disease activity as measured by total BPDAI (r = 0.918; P = .06). Also, 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).

“The novel ELISA may be helpful to identify patients with bullous pemphigoid who are suitable candidates for anti-IgE therapy,” van Beek et al. concluded. They said further that while IgE anti-BP180 reactivity was not associated with a distinct clinical presentation, IgG autoantibodies against BP180 NC16A were related to the classic blistering phenotype.

In accompanying editorial by T Hashimoto, D. Tsuruta and N. Ishii, observed, “The results of the study by van Beek et al. confirmed that IgE anti-BP180 autoantibodies are present in considerable numbers of BP sera. Because previous reports suggested that BP patients with IgE autoantibodies are responsive to omalizumab therapy, reliable ELISAs should be used to help select patients with BP who are suitable for omalizumab therapy.”

 

 

 

 

References:

 N van Beek, N Lüttmann, et al. “Correlation of Serum Levels of IgE Autoantibodies Against BP180 With Bullous Pemphigoid Disease Activity,”

JAMA Dermatology.

January 2017. DOI:10.1001/jamadermatol.2016.3357.  Takashi Hashimoto, MD; Daisuke Tsuruta, MD, PhD; Norito Ishii, MD. “Immunoglobulin E Autoantibodies in Bullous Pemphigoid Detected by Immunoglobulin E Enzyme-Linked Immunosorbent Assays,”

JAMA Dermatology

. January 2017. DOI:10.1001/jamadermatol.2016.4593

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