Pregnant women have increased incidence of IgE autoantibodies reactive with the skin and placental antigen BP180 (type XVII collagen)

Abstract

BP180 (type XVII collagen) is a transmembrane protein expressed in a variety of cell types. It is also the target of autoantibodies in cutaneous autoimmune disease including bullous pemphigoid and pemphigoid gestationis, a disease unique to pregnancy. The purpose of this study was to determine the prevalence and specificity of cutaneous autoantibodies in a cohort of pregnant women. De-identified sera were collected from pregnant women (n = 299) and from non-pregnant controls (n = 134). Sera were analyzed by ELISA for the presence of IgG and IgE autoantibodies directed against several cutaneous autoantigens. IgE antibodies against the NC16A domain of BP180 were detected in 7.7% of pregnant women, compared to 2.2% of healthy controls (p = 0.01). No increase in total or cutaneous autoantigen specific IgG was seen. Total serum IgE was within the normal range. Full-length BP180 was detected by western immunoblot in epidermal, keratinocyte, placental and cytotrophoblast (CTB) cell lysates. Furthermore, flow cytometry and indirect immunofluorescence confirmed the expression of BP180 on the surface of cultured CTBs. Finally, it was demonstrated that IgE antibodies in the pregnancy sera labeled not only cultured CTBs, but also the placental amnion and cutaneous basement membrane zone using indirect immunofluorescence. We conclude that some pregnant women develop antibodies specific for BP180, and that these autoantibodies are capable of binding both CTB and the placental amnion, potentially affecting placental function.

Value of BIOCHIP Technology in the Serological Diagnosis of Pemphigoid Gestationis

“…The complete absence of anti-BP180 IgG auto-antibodies in healthy para is in line with previous reports on the frequency of anti-BP180 IgG auto-antibodies in healthy blood donors and in healthy pregnant women (14,15), indicating that anti-BP180 NC16A IgG auto-antibodies do not emerge in healthy pregnancies. However, in some patients with PG, low titres of anti-BP180 auto-antibodies were detectable by ELISA, but mostly remained too low to reach the assay's cut-off value (7).…”

Missing the target: Characterization of bullous pemphigoid patients who are negative using the BP180 enzyme-linked immunosorbant assay

“…The autoantibody mapping studies were carried out using recombinant proteins or human epidermal extracts, 26 a standard immunoblotting protocol. 19 Sera of patients or control subjects were preadsorbed with a bacterial cell lysate containing recombinant GST to eliminate reactivity with this moiety of the fusion proteins.…”

IgE-mediated mechanisms in bullous pemphigoid and other autoimmune bullous diseases

“…[88] In contrast, in 7.7% of 299 pregnant women, anti-BP180 IgE was detected and was shown to label both the cutaneous BMZ and the placental amnion by indirect IF microscopy as well as cultured cytothrophoblasts. [126] IgE binding along the BMZ in the patients' skin was found in 69% of 13 mucous membrane pemphigoid patients [83] but in none of 2 and 12 patients with pemphigoid gestationis. [127,128] Pemphigus Elevated total IgE serum levels were found in patients with endemic pemphigus foliaceus but rarely in pemphigus vulgaris.…”