Pemphigoid Gestationis Patients Produce IgG1 Antibodies Against BP180 Epitopes

Silke Hofmann, MD

A recent investigation on pemphigoid gestationis (PG) found that patients with the rare autoimmune blistering disorder predominantly produce IgG1 autoantibodies against bullous pemphigoid (BP180) epitopes.

The disorder, which occurs in people who are pregnant, is often characterized by itchy erythematous papules, plaques, and blisters that typically spread. It has affected roughly 10% of all pregnancies, with the transfer of maternal antibodies at times leading to neonatal pemphigoid (NP).

Previous studies suggested that the disorder is caused by immunoglobulin G (IgG) antibodies against the NC16A domain of collagen XVII.

The significance of these antibodies had been unsure, which prompted investigators led by Silke Hofmann, MD, Department of Dermatology, University of Freiberg, Germany, to investigate the role they play in pemphigoid gestationis.

The Methods

Between 2010 and 2018, Hofmann and colleagues characterized cases of pemphigoid gestationis recorded at the University of Freiburg through standard diagnostic tests which included histopathology, direct and indirect immunofluorescence, and enzyme-linked immunosorbent assay (ELISA).

Immunoblot analyses were used to characterize specific immune profiles, and patient material and clinical data were recorded in accordance with the Declaration of Helsinki and Institutional Guidelines.

A total of 11 patients with pemphigoid gestationis were identified at the University of Freiburg. The patients ranged from 24 to 41 years, and all described intense pruritus.

Of those patients, a total of 6 presented with periumbilical lesions, while 5 had predominantly acral lesions.

Hofmann and colleagues performed a direct immunofluorescence (DIF) test on each patient to examine tissue-bound autoantibodies.

The Findings

Results from the DIF testing revealed linear complement C3c, C4d, discrete to strong linear IgG, and strong IgG1 depositions along the basement membrane zone (BMZ) in all patients. However, no Ig4, IgE, or IgA depositions were observed.

Tissue eosinophilia was identified in 6 of the 7 biopsies featured in the study, and blood eosinophilia was recorded in 2 cases.

Hofmann and investigators noted that antibodies against the full-lenth BP180 form (FL BP180) were present in 88% of all patients.

A routine BP180 NC16A ELISA test result was negative in 2 patients, both of whom had FL BP180 and BP230 autoantibodies.

An immunoblot analyses showed IgG antibodies reacted against extracellular epitopes LAD1 and LABD97 in 63% of available serum samples (5 of 8 patients), with additional reactivity against FL BP180 in 3 of 8 patients.

Overall, the investigators believed their study findings on IgG4 predominance was in accordance with previous reports, adding that it emphasized the importance of complement fixation in pemphigoid gestationis.

They added that BP180 NC16A ELISA has a reported sensitivity of 86% to 97%, and recommended it for diagnostic testing, with the present study revealing that antibodies against both FL BP180 and BP230 could also cause pemphigoid gestationis.

Limitations for the present study included a lack of full0lenght minus NC16A BP180 enzyme-linked immunosorbent assay, which investigators believe could be corrected in future studies.

“An evaluation of larger cohorts, ideally based on an international registry, would be of major importance to correlate the clinical course to an autoimmune profile in patients with PG,” the team wrote.

The study, “Autoreactivity to BP180 Neoepitopes in Patients With Pemphigoid Gestationis,” was published online in JAMA Dermatology.