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.
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.
Authors: Hideyuki Ujiie; David Rosmarin; Michael P Schön; Sonja Ständer; Katharina Boch; Martin Metz; Marcus Maurer; Diamant Thaci; Enno Schmidt; Connor Cole; Kyle T Amber; Dario Didona; Michael Hertl; Andreas Recke; Hanna Graßhoff; Alexander Hackel; Anja Schumann; Gabriela Riemekasten; Katja Bieber; Gant Sprow; Joshua Dan; Detlef Zillikens; Tanya Sezin; Angela M Christiano; Kerstin Wolk; Robert Sabat; Khalaf Kridin; Victoria P Werth; Ralf J Ludwig Journal: Front Med (Lausanne) Date: 2022-06-09