Pathogenic relevance of antibodies against desmoglein 3 in patients with oral lichen planus

Summary Background and objectives Oral lichen planus (OLP) is a T cell driven disorder that significantly impairs patients’ quality of life. Previous reports suggest that both cellular and humoral activities against desmoglein (dsg) 1 and 3 may be involved in OLP pathogenesis. Here, we aim to analyze the frequency of occurrence and pathological significance of anti‐dsg antibodies in a large cohort of OLP patients. Materials and methods OLP patients were screened for anti‐dsg antibodies by enzyme‐linked immunosorbent assay in three tertiary referral centers. OLP sera with anti‐dsg antibodies were further analyzed by Western blot and dispase‐based keratinocyte dissociation assay (DDA) to identify the targeted dsg ectodomains and to assess their pathogenicity. Results Of 151‐screened individuals with OLP, only four patients (2.6%) with erosive OLP showed serum IgG against dsg1/3. Western blot analysis with recombinant dsg3 ectodomains revealed preferential recognition of the extracellular domain 5. By DDA with spontaneously immortalized human keratinocytes, none of the sera from these four patients induced acantholysis. Conclusions Activation of humoral immunity occurs prevalently in patients with erosive OLP, probably due to epitope spreading. OLP serum antibodies are unable to induce loss of intercellular adhesion in vitro, strongly suggesting that they are not disease causing but rather an epiphenomenon.