IngentaConnect Comparison of reactivity and epitope recognition between sera fro...

Authors: Mignogna, M.¹; Lanza, A.²; Rossiello, L.³; Ruocco, V.¹; Ahmed, A. R.

Source: Clinical & Experimental Immunology, Volume 145, Number 1, July 2006 , pp. 28-35(8)

Abstract:

Summary

Mucous membrane pemphigoid (MMP) (also known as cicatricial pemphigoid) is a rare autoimmune mucocutaneous blistering disease that affects mucous membranes derived from stratified squamous epithelium and the skin. A subset of MMP affects only the oral cavity and is referred to as the oral pemphigoid (OP). MMP and OP are characterized by subepithelial vesicles on histology and in vivo deposition of immunoglobulins and complement at the basement membrane zone (BMZ) on immunopathology. Previous studies have shown that sera of patients with MMP bind to human integrin β4, while sera of patients with oral pemphigoid bind to the integrin α6 component of the heterodimer. The prognosis in MMP is grave but excellent in OP. In this study we compare the binding of sera from patients with OP from Boston, MA, USA to Naples, Italy, and attempt to identify an epitope to which the anti-integrin α6 human autoantibody binds. Our results indicate that the sera from Boston and Naples are identical in their reactivity. They recognize a fragment I (AA 23-462) and its subfragment IB (AA 217-462) only, in the human integrin α6 molecule. Blocking studies, immunoprecipitation and immunoabsorbtion studies confirm the presence of this single 245 AA region. Antibodies to subfragment IB cause BMZ separation in organ culture using normal human oral mucosa as substrate. This preliminary study indicates that patients on both continents may have similar reactivity and suggests that an intercontinental study group could be established to advance our understanding of the pathogenesis of OP and the biology of anti-α6 integrin autoantibodies.

Keywords: anti-integrin α6 subunit antibody; epitope binding; Italian and US patients; mucous membrane pemphigoid; oral pemphigoid

Document Type: Research article

DOI: 10.1111/j.1365-2249.2006.03103.x

Affiliations: 1: Department of Odontostomatological and Maxillofacial Sciences, University of Naples, School of Medicine, Naples, Italy, 2: Department of Odontostomatological, Ortodontical and Surgical Disciplines, Dentistry School, 2nd University of Naples, Italy, and 3: Department of Dermatology, 2nd University of Naples, Italy

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Comparison of reactivity and epitope recognition between sera from American and Italian patients with oral pemphigoid