Antigen Specificity in Subsets of Mucous Membrane Pemphigoid

Abstract

Mucous membrane pemphigoid (MMP) has several subsets based on target antigens recognized by their sera. MMP and ocular cicatricial pemphigoid (OCP) sera recognize beta4 integrin subunit, oral pemphigoid sera recognize alpha6 integrin subunit, and anti-epiligrin cicatricial pemphigoid sera recognize laminin 5. Our aim is to determine if autoantibodies in the sera of patients with MMP, OCP, and oral pemphigoid (OP) recognize only their target antigens, and to see if this specificity is maintained throughout the clinical course. An immunoblot assay using bovine gingival lysate was used as substrate. Fifteen MMP patients, eight with OCP, and 15 OP patients were studied before therapy and at multiple intervals during the clinical course. Absorption and blocking studies were performed to determine binding specificity. Sera of patients with MMP and OCP recognize only beta4 integrin subunit, and sera of OP patients recognize alpha6 integrin throughout the clinical course. The sera of patients in the subsets of MMP described in this report show adherence and selectivity to target antigen during the entire clinical course, without crossover, interaction, or change. Hence, these subsets of MMP provide an excellent model to study clinical correlation with antigen and antibody specificity, in autoimmunity.

Mucous membranepemphigoid in two half-sisters. The potential roles of autoantibodies to β4 integrin subunits and HLA-DQβ1*0301.

“…12 Antibodies to β4-integrin subunits also correlated with acute clinical flares, but the titer level was not detectable during remission. In the older sister, antibodies to BPAg1 and BPAg2 were detected by ELISA and the levels did not correlate with clinical disease.…”

Identification of Epitopes Within Integrin β4 for Binding of Auto-Antibodies in Ocular Cicatricial and Mucous Membrane Pemphigoid: Preliminary Report

“…Cross-reactivity between antibodies to integrin a6 and b4 has not been observed. 17,19 Furthermore, auto-antibody titers to integrin b4 are high during active disease and decline with improvement. 27 Similarly, a correlation with disease activity has been reported with autoantibodies to a6 integrin in oral pemphigoid (OP).…”

“…17 Mucous membrane pemphigoid, OCP, and both OCP and MMP sera continue to bind to b4 integrin. Cross-reactivity between antibodies to integrin a6 and b4 has not been observed.…”

“…16 It is divided into subsets by clinical presentation and antigen specificity. 17 The version of the disease that is localized to the oral cavity is known as oral pemphigoid. 18 The target antigen is integrin a6.…”

Bullous Pemphigoid, Mucous Membrane Pemphigoid and Pemphigus Vulgaris: An Update on Pathobiology

“…MMP patients have been shown to have antibodies that recognize BP230, 97/120 kDa linear IgA bullous dermatosis (LAD) antigen, laminin 332 (laminin 5) and 331 (laminin 6), and type VII collagen [59,60]. Studies have also linked oral MMP to the α6-integrin subunit, and both generalized and ocular MMP to the β4-integrin subunit [61].…”