Editor Comment

Mucous membrane pemphigoid (MMP) is no longer considered as single clinical or immunological disease entity.
Advances in molecular biology have unravelled several different antigenic structures which are involved in different subtypes of MMP.

 

In this paper, Rashid, Stern and Ahmed suggest that oral pemphigoid (OP) is a distinct entity with epitope for the binding of autoantibodies within the integrin a₆ subunit (A, B, C and D).
OP is clinically characterized as a pemphigoid limited to the oral mucosa with no extra-oral engagements. Sera of 20 patients with active OP were studied. All sera bound to integrin a₆ in DU145 cell lysate by immuno-precipitation and immunoblot assay.

The same sera bound only to fragment A and its subfragment A2 on an immunoblot assay. Controls were sera samples from 10 healthy volunteers and 40 patients with other variants of mucous membrane pemphigoid and mAb GoH3 and BQ16 to integrin a₆.

Control sera did not bind to the full-length integrin a₆  subunit nor any of the cloned fragments.

 

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Abstract (Link to Pub Med Abstract)

Oral pemphigoid (OP) is a rare chronic autoimmune disease characterized by blisters and erosive lesions in the oral mucosa. We identified an epitope for the binding of OP autoantibodies within the integrin a₆ subunit, by cloning four overlapping fragments (A, B, C, and D). Immunoperoxidase studies demonstrated that all of the fragments were present in the oral mucosa.
Sera of 20 patients with active OP were studied. All sera bound to integrin a₆  in DU145 cell lysate by immunoprecipitation and immunoblot assay. The same sera bound only to fragment A and its subfragment A2 on an immunoblot assay. The specificity of the binding was further characterized by blocking and cross-absorption studies. A 14-aa synthetic peptide A2.1, within fragment A2, bound to all the test sera. The sera in this study bound to only one epitope. Controls were sera samples from 10 healthy volunteers and 40 patients with other variants of mucous membrane pemphigoid and mAb GoH3 and BQ16 to integrin a₆.
Control sera did not bind to the full-length integrin a₆ subunit nor any of the cloned fragments. The OP patient sera and immunoaffinity-purified OP sera, rabbit antisera against fragments A and A2, and mAb GoH3 produced basement membrane separation of oral mucosa in organ culture.
This study identifies a peptide within the extracellular domain of integrin a₆  molecule, to which Abs in the sera from patients with OP bind, and which may play an important role in the pathogenesis of OP.