Prospective studies on the routine use of a novel multivariant enzyme-linked immunosorbent assay for the diagnosis of autoimmune bullous diseases

J Am Acad Dermatol. 2017 May;76(5):889-894.e5. doi: 10.1016/j.jaad.2016.11.002. Epub 2016 Dec 28.


Background: Serologic diagnosis of autoimmune blistering disease (AIBD) usually follows a sophisticated multistep algorithm.

Objective: We sought validation of a multivariant enzyme-linked immunosorbent assay (ELISA) in the routine diagnosis of AIBD.

Methods: The multivariant ELISA comprising 6 recombinant immunodominant forms of major AIBD target antigens, ie, desmoglein 1, desmoglein 3, envoplakin, BP180, BP230, and type VII collagen was applied in: (1) a cohort of well-characterized AIBD (n = 173) and control sera (n = 130), (2) a prospective multicenter study with 204 sera from patients with newly diagnosed AIBD with positive direct immunofluorescence microscopy, and (3) a prospective monocenter study with 292 consecutive sera from patients with clinical suspicion of AIBD in comparison with the conventional multistep diagnostic algorithm.

Results: Concordant results in the multivariant ELISA compared with direct immunofluorescence microscopy were seen in 94% of patients with pemphigus and 71% of patients with pemphigoid (Cohen κ value, 0.95 and 0.66) and with the conventional multistep diagnostic approach in 91% of patients with pemphigus and 88% of patients with bullous pemphigoid and 93% of autoantibody-negative sera (Cohen κ, 0.95, 0.84, and 0.78).

Limitations: IgA autoantibodies and less common target antigens were not analyzed.

Conclusions: The multivariant ELISA is a practical, highly standardized, and widely available novel diagnostic tool for the routine diagnosis of AIBD.

Keywords: autoantibody; blistering; bullous pemphigoid; epidermolysis bullosa acquisita; pemphigus.

Publication types

  • Multicenter Study
  • Validation Study

MeSH terms

  • Algorithms
  • Autoantigens / blood
  • Autoimmune Diseases / blood*
  • Autoimmune Diseases / diagnosis*
  • Collagen Type VII / blood
  • Collagen Type XVII
  • Desmoglein 1 / blood
  • Desmoglein 3 / blood
  • Dystonin / blood
  • Enzyme-Linked Immunosorbent Assay / methods
  • Fluorescent Antibody Technique, Direct
  • Humans
  • Membrane Proteins / blood
  • Microscopy
  • Non-Fibrillar Collagens / blood
  • Prospective Studies
  • Protein Precursors / blood
  • ROC Curve
  • Recombinant Proteins / immunology
  • Skin Diseases, Vesiculobullous / blood*
  • Skin Diseases, Vesiculobullous / diagnosis*


  • Autoantigens
  • Collagen Type VII
  • DST protein, human
  • Desmoglein 1
  • Desmoglein 3
  • Dystonin
  • Membrane Proteins
  • Non-Fibrillar Collagens
  • Protein Precursors
  • Recombinant Proteins
  • envoplakin