A sensitive and specific assay for the serological diagnosis of antilaminin 332 mucous membrane pemphigoid

Br J Dermatol. 2019 Jan;180(1):149-156. doi: 10.1111/bjd.17202. Epub 2018 Nov 1.

Abstract

Background: Antilaminin 332 mucous membrane pemphigoid (MMP) is an autoimmune subepidermal blistering disease with predominant mucosal involvement and autoantibodies against laminin 332. Malignancies have been associated with this disease; however, no standardized detection system for antilaminin 332 serum antibodies is widely available.

Objectives: Development of a sensitive and specific assay for the detection of antilaminin 332 antibodies.

Methods: An indirect immunofluorescence (IF) assay using recombinant laminin 332 was developed and probed with a large number of antilaminin 332 MMP patient sera (n = 93), as well as sera from patients with antilaminin 332-negative MMP (n = 153), bullous pemphigoid (n = 20), pemphigus vulgaris (n = 20) and noninflammatory dermatoses (n = 22), and healthy blood donors (n = 100).

Results: In the novel IF assay, sensitivities with the laminin 332 heterotrimer and the individual α3, β3 and γ2 chains were 77%, 43%, 41% and 13%, respectively, with specificities of 100% for each substrate. The sensitivity for the heterotrimer increased when an anti-IgG4 enriched antitotal IgG conjugate was applied. Antilaminin 332 reactivity paralleled disease activity and was associated with malignancies in 25% of patients with antilaminin 332 MMP.

Conclusions: The novel IF-based assay will facilitate the serological diagnosis of antilaminin 332 MMP and may help to identify patients at risk of a malignancy.

MeSH terms

  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Autoantigens / immunology*
  • Cell Adhesion Molecules / immunology*
  • Cohort Studies
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Kalinin
  • Pemphigoid, Benign Mucous Membrane / blood
  • Pemphigoid, Benign Mucous Membrane / diagnosis*
  • Recombinant Proteins / immunology
  • Sensitivity and Specificity
  • Serologic Tests / methods

Substances

  • Autoantibodies
  • Autoantigens
  • Cell Adhesion Molecules
  • Recombinant Proteins