Evaluation of Site- and Autoantigen-Specific Characteristics of Mucous Membrane Pemphigoid

Abstract

ucous membrane pemphigoid (MMP) is a rare subepithelial autoimmune bullous disease typified by predominant mucosal involvement and scarring. 1 It poses a substantial diagnostic challenge owing to the generally lower levels of serum autoantibodies compared with other autoimmune bullous diseases. The heterogeneity of autoantigens targeted in MMP, autoantibody isotypes (immunoglobulin [Ig] IgG, IgA, or both), and the lack of widely available serological assays further hamper early recognition of MMP. Given the rarity of the disease, data about the association of clinical and immunopathological features of the disease are limited. The aim of the current study was to investigate the clinical, immunoserological, and immunopathological characteristics of a large cohort of patients with MMP managed in 2 tertiary centers. MethodsWe performed a retrospective cohort study that included routine data from all patients diagnosed with MMP between January 1, 2007, and February 28, 2020, in 2 referral centers for autoimmune bullous diseases at the

Molecular Basis for Global Incidence of Pemphigoid Diseases and Differences in Phenotypes

“…These reported peptides were also present in the computer models in this study. Likewise, studies using in vitro systems identified T cell epitopes in BP230 (15). Similar peptides were identified in the computer model in this study.…”

“…Most studies have concentrated on the NC16A domain of BP180 in the process of generating pemphigoid specific autoreactive T cells (57,58). Researchers have discovered that peptides other than those in the NC16A domain for BP180 and other peptides in BP230 can also be involved in autoreactive T cells in pemphigoid (15,36). Studies showed that T cells react with the entire peptide and with sequences 490-534 and 507-534 (57,58).…”

“…In BP, the anti-BMZ autoantibodies are directed against BP antigen 1 (BPAG1 or BP230) and BP antigen 2 (BPAG2 or BP180) (14,15). In a large cohort of patients from Germany, in a recent study, the most frequently targeted antigen was BP180 (15). Their injection produces blisters in the skin of neonatal mice (16,17).…”

A Probing of the Issue of Detecting IgG, IgG4 and IgA Antibodies to Laminin 332 Epitopes in Mucous Membrane Pemphigoid: A Clinical-Laboratory Experience of a Single Central European University Dermatology Department

“…It is postulated that the response might be as a result of specific genetic factors or due to a continued antigenic stimulation affecting the normal distribution of IgG leading to IgG4 restricted response. Interestingly, van Beek et al 20 indicated that IgG4 autoimmune response against α3 chain of Ln-332 may be linked to malignancy. Our observations support the notion that IgG4 autoantibodies may preferentially bind to α3 subunit; however, we did not detect cancer in our patient having such antibodies.…”

“…It was reported that LAD-1, a shedding extracellular fragment of BP180, which is the autoantigen in lamina lucida type of linear IgA bullous dermatosis (ll LABD) 24 , 25 is the most frequently detected autoantigen in MMP. 20 This suggests that there is a molecular relationship between MMP and ll LABD, and that in MMP autoimmunity mediated by Ln-332 has limited pathogenic potential compared to that mediated by LAD-1. As far as diagnostic work-up is concerned, it suggests that performing ELISA and mosaic IIF serological studies on MMP-suspected individuals with just routinely used NC16A epitope of BP180 is not enough to detect autoimmunity, and that traditional unsophisticated ssIIF, somewhat paradoxically, is better suited for this purpose, according to our laboratory experience.…”