title: Development of antigen-specific ELISA for circulating autoantibodies to extracellular matrix protein 1 in lichen sclerosus.
abstract: Lichen sclerosus is a common, acquired chronic inflammatory skin disease of unknown etiology, although circulating autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been detected in most patients' sera. We have examined the nature of ECM1 epitopes in lichen sclerosus sera, developed an ELISA system for serologic diagnosis, and assessed clinicopathological correlation between ELISA titer and disease. Epitope-mapping studies revealed that lichen sclerosus sera most frequently recognized the distal second tandem repeat domain and carboxyl-terminus of ECM1. We analyzed serum autoantibody reactivity against this immunodominant epitope in 413 individuals (95 subjects with lichen sclerosus, 161 normal control subjects, and 157 subjects with other autoimmune basement membrane or sclerosing diseases). The ELISA assay was highly sensitive; 76 of 95 lichen sclerosus patients (80.0%) exhibited IgG reactivity. It was also highly specific (93.7%) in discriminating between lichen sclerosus and other disease/control sera. Higher anti-ECM1 titers also correlated with more longstanding and refractory disease and cases complicated by squamous cell carcinoma. Furthermore, passive transfer of affinity-purified patient IgG reproduced some histologic and immunopathologic features of lichen sclerosus skin. This new ELISA is valuable for the accurate detection and quantification of anti-ECM1 autoantibodies. Moreover, the values may have clinical significance in patients with lichen sclerosus.
authors.affiliation: Genetic Skin Disease Group, Department of Immunofluorescence, St. John's Institute of Dermatology, The Guy's, King's College and St. Thomas' Hospitals' Medical School, London, United Kingdom.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Oyama
authors.forename: Ien
authors.initials: I
authors.lastname: Chan
authors.forename: Sallie M
authors.initials: SM
authors.lastname: Neill
authors.forename: Andrew P
authors.initials: AP
authors.lastname: South
authors.forename: Fenella
authors.initials: F
authors.lastname: Wojnarowska
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kawakami
authors.forename: David
authors.initials: D
authors.lastname: D'Cruz
authors.forename: Kirti
authors.initials: K
authors.lastname: Mepani
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Hughes
authors.forename: Balbir S
authors.initials: BS
authors.lastname: Bhogal
authors.forename: Fumio
authors.initials: F
authors.lastname: Kaneko
authors.forename: Martin M
authors.initials: MM
authors.lastname: Black
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000276:immunology; D005982:Glutathione Transferase / Q000235:genetics / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D018459:Lichen Sclerosus et Atrophicus / Q000175:diagnosis* / Q000276:immunology; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D001323:Autoantibodies; C490607:ECM1 protein, human; C094556:Ecm1 protein, mouse; D016326:Extracellular Matrix Proteins; D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase