Prevalence and clinical significance of anti-laminin 332 autoantibodies detected by a novel enzyme-linked immunosorbent assay in mucous membrane pemphigoid

JAMA Dermatol. 2013 May;149(5):533-40. doi: 10.1001/jamadermatol.2013.1434.

Abstract

Importance: A rare variant of mucous membrane pemphigoid (MMP) is characterized by circulating anti-laminin 332 (Lam332) autoantibodies and seems to be associated with concurrent malignant neoplasms.

Objective: To determine the prevalence and clinical significance of anti-Lam332 autoantibody detection from a large series of patients with MMP.

Design: Multicenter retrospective study.

Setting: Four French national centers for autoimmune bullous diseases.

Participants: One hundred fifty-four patients with MMP and 89 individuals serving as controls were included.

Interventions: Serum samples were analyzed by a new Lam332 enzyme-linked immunosorbent assay (ELISA); clinical and immunopathologic data were obtained from the patients' medical records.

Main outcome measures: The Lam332 ELISA scores were evaluated with respect to clinical characteristics, standard and salt-split indirect immunofluorescence, and bullous pemphigoid (BP) 230 and BP180-NC16A ELISAs.

Results: The Lam332 ELISA score was positive (≥9 U/mL) in 20.1% of serum samples from patients with MMP, 1 of 50 patients with bullous pemphigoid (BP), none of 7 with pemphigus, and 3 of 32 other controls. No relationship was evidenced between a positive ELISA Lam332 score and age; sex ratio; oral, ocular, genital, skin, or esophageal/laryngeal involvement; internal malignant neoplasm; or BP180 ELISA score. Salt-split skin indirect immunofluorescence and ELISA BP230 results were more frequently positive when Lam332 ELISA results were positive (P = .04 and .02, respectively). Patients with a positive Lam332 ELISA score frequently had more severe MMP (67.8% vs 47.2%; P = .04).

Conclusions and relevance: Results of this novel ELISA showed that serum anti-Lam332 autoantibodies are detected in 20.1% of patients with MMP. Anti-Lam332 autoantibodies are mainly detected in patients with severe MMP but not preferentially in those with a malignant neoplasm. The association between anti-Lam332 and anti-BP230 autoantibodies might arise from an epitope-spreading phenomenon.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Autoantibodies / isolation & purification
  • Carrier Proteins
  • Case-Control Studies
  • Cell Adhesion Molecules / immunology*
  • Chi-Square Distribution
  • Child
  • Cytoskeletal Proteins
  • Dystonin
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • France
  • Humans
  • Kalinin
  • Male
  • Membrane Glycoproteins / immunology
  • Middle Aged
  • Neoplasms / blood*
  • Nerve Tissue Proteins
  • Pemphigoid, Benign Mucous Membrane / blood*
  • Retrospective Studies
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Young Adult

Substances

  • Autoantibodies
  • Carrier Proteins
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • DST protein, human
  • Dystonin
  • Membrane Glycoproteins
  • Nerve Tissue Proteins