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.