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Prevalence and Clinical Significance of Anti–Laminin 332 Autoantibodies Detected by a Novel Enzyme-Linked Immunosorbent Assay in Mucous Membrane Pemphigoid

Philippe Bernard, MD, PhD; Frank Antonicelli, PhD; Christophe Bedane, MD, PhD; Pascal Joly, MD, PhD; Christelle Le Roux-Villet, MD; Sophie Duvert-Lehembre, MD; Patricia Rousselle, PhD; Catherine Prost-Squarcioni, MD, PhD
JAMA Dermatol. 2013;149(5):533-540. doi:10.1001/jamadermatol.2013.1434.
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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.

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Figure. Scatterplot representation of enzyme-linked immunosorbent assay (ELISA) laminin 332 (Lam332) results concerning the performance of serum samples from 154 patients with mucous membrane pemphigoid (MMP) and 89 controls, including 32 patients without autoimmune diseases (NC). All serum samples were tested in duplicate; plotted dots represent the mean of the Lam332 ELISA scores obtained for each sample. The horizontal dotted line indicates the upper level of normal for the Lam332 ELISA score. BP indicates bullous pemphigoid.

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