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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Identification of a basement membrane zone antigen reactive with circulating IgA antibody in ocular cicatricial pemphigoid.

Ocular cicatricial pemphigoid is a rare vesiculobullous disease characterized by linear deposition of IgG and/or IgA along the basement membrane zone of conjunctival biopsies. This study identifies a tissue antigen detected by ocular cicatricial pemphigoid patient sera. Patient selection was based on the presence of only ocular involvement and a positive direct immunofluorescence of conjunctiva. We evaluated patient and control sera using indirect immunofluorescence of basement membrane zone separated skin, Western blot, and purified antibodies from nitrocellulose and epidermal sheets. Direct immunofluorescence performed on the patients' conjunctival biopsy showed linear deposition of IgA along the basement membrane zone in all seven patients, and five of seven also demonstrated deposition of IgG along the basement membrane zone. Indirect immunofluorescence performed on the patients' sera demonstrated linear deposition of IgA along the epidermal side of the basement membrane zone of ethylenediaminetetraacetic acid-separated skin in all seven patients. IgA titers ranged from 1:20 to 1:80. No IgG was detected. Immunoblots detected IgA binding to a 45-kD antigen in all patients as well as sporadic IgA binding to a number of other proteins. Immunoblots stained with sera from patients did not show reactivity to the 230- or 180-kD bullous pemphigoid antigens or the 97-kD linear IgA bullous dermatosis antigen. Eluting IgA from the 45-kD region and other regions revealed that only antibodies eluted from the 45-kilodalton region bound linearly to the basement membrane on separated skin. Purification of IgA using epidermal sheets confirmed that the antibody responsible for staining on indirect immunofluorescence bound to the 45-kD region on Western blot. Sera from normals and patients with bullous pemphigoid, dermatitis herpetiformis, and linear IgA bullous dermatosis failed to demonstrate basement membrane zone IgA on elution of the 45-kD region. We conclude that these ocular cicatricial pemphigoid sera contain a unique IgA antibody that binds to a 45-kD basement membrane zone antigen.[1]


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