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

Abstract

Importance:A rare variant of mucous membrane pemphigoid (MMP) is characterized by circulating antilaminin 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. 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 (Ն9 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. AntiLam332 autoantibodies are mainly detected in patients with severe MMP but not preferentially in those with a malignant neoplasm. The association between antiLam332 and anti-BP230 autoantibodies might arise from an epitope-spreading phenomenon.

A systematic review with pooled analysis of clinical presentation and immunodiagnostic testing in mucous membrane pemphigoid: association of anti‐laminin‐332 IgG with oropharyngeal involvement and the usefulness of ELISA

“…IgG antibodies to laminin‐332 are detected in some MMP patients, but not in BP patients . Previous studies of IgG reactivity against laminin‐332 demonstrated positivity in 20% of MMP patients, with no association with a distinct clinical phenotype . However, they additionally did not demonstrate an association with malignancy which was later identified by the specific study of laminin 332‐reactive MMP patients .…”

Diagnosis of autoimmune bullous diseases

“…Various other ELISAs have been reported, including those for detection of IgE antibodies against BP180 NC16A and for detection of serum reactivity against desmocollins , laminin γ1 , the ectodomain of BP180 , full‐length BP180 , laminin 332 , and various other forms of BP180 . Some recent ELISA systems have not yet been standardized and are only available in specialized laboratories.…”

Diagnostik blasenbildender Autoimmundermatosen

“…Außerdem wurden verschiedene weitere ELISAs beschrieben, unter anderem für den Nachweis von IgE‐Antikörpern gegen BP180 NC16A und den Nachweis einer Serumreaktivität gegen Desmocolline , Laminin γ1 , die Ektodomäne von BP180 , das BP180‐Gesamtprotein , Laminin 332 und verschiedene andere Formen von BP180 . Einige der neu entwickelten ELISA‐Systeme sind noch nicht standardisiert und stehen nur in Speziallaboratorien zur Verfügung.…”