Bullous pemphigoid and mucous membrane pemphigoid humoral responses differ in reactivity towards BP180 midportion and BP230

Front Immunol. 2024 Nov 29:15:1494294. doi: 10.3389/fimmu.2024.1494294. eCollection 2024.

Abstract

Background: Bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP) are rare autoimmune blistering disorders characterized by autoantibodies (autoAbs) targeting dermo-epidermal junction components such as BP180 and BP230. The differential diagnosis, based on both the time of appearance and the extension of cutaneous and/or mucosal lesions, is crucial to distinguish these diseases for improving therapy outcomes and delineating the correct prognosis; however, in some cases, it can be challenging. In addition, negative results obtained by commercially available enzyme-linked immunosorbent assays (ELISAs) with BP and MMP sera, especially from patients with ocular involvement, often delay diagnosis and treatment, leading to a greater risk of poor outcomes.

Objectives: Our aim was to find potentially different reactivity profiles in BP and MMP and improve available approaches for diagnosis with focus on ocular MMP.

Methods: Two cohorts of 90 BP and 90 MMP, recruited from different Italian clinical centers, were characterized also employing a novel ELISA based on the BP180 extracellular domain (ECD-BP180).

Results: Immunoglobulin G (IgG) reactivity to BP180 and BP230 in MMP sera was significantly reduced in comparison with BP, mostly affecting BP230 and E-1080 (53% and 36% in BP vs. 11% and 3% in MMP, respectively, p < 0.0001). The combined sensitivity of BP180-NC16A and ECD-BP180 ELISAs was greater compared to BP180-NC16A and BP230 ELISAs both in BP (97% and 92%, respectively) and in MMP (42% and 31%, respectively). The present study shows that MMP patients with ocular involvement rarely reacted to BP180 by IgG in contrast with patients with oral and/or cutaneous involvement (p = 0.0245 and p = 0.0377, respectively), suggesting that an oral and/or cutaneous MMP positive to BP180 hardly evolves to ocular MMP. Of note, one-third of ocular MMP showed immunoglobulin A (IgA) reactivity to ECD-BP180 by immunoblotting.

Conclusions: The present study provides several hints to perform a correct and timely diagnosis in BP and MMP, which is crucial for improving therapy outcomes and delineating the correct prognosis.

Keywords: autoantibody; autoantigen; bullous pemphigoid; epitope; humoral response; mucous membrane pemphigoid.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Autoantibodies* / blood
  • Autoantibodies* / immunology
  • Autoantigens* / immunology
  • Collagen Type XVII*
  • Diagnosis, Differential
  • Dystonin* / immunology
  • Enzyme-Linked Immunosorbent Assay*
  • Female
  • Humans
  • Immunity, Humoral
  • Immunoglobulin G* / blood
  • Immunoglobulin G* / immunology
  • Male
  • Middle Aged
  • Non-Fibrillar Collagens* / immunology
  • Pemphigoid, Benign Mucous Membrane* / blood
  • Pemphigoid, Benign Mucous Membrane* / diagnosis
  • Pemphigoid, Benign Mucous Membrane* / immunology
  • Pemphigoid, Bullous* / blood
  • Pemphigoid, Bullous* / diagnosis
  • Pemphigoid, Bullous* / immunology

Substances

  • Collagen Type XVII
  • Non-Fibrillar Collagens
  • Autoantigens
  • Dystonin
  • DST protein, human
  • Autoantibodies
  • Immunoglobulin G

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This article was partially supported by the “Progetto Ricerca Corrente” of the Italian Ministry of Health.