THE 97 KDA LINEAR IGA BULLOUS DISEASE ANTIGEN IS IDENTICAL TO A PORTION OF THE EXTRACELLULAR DOMAIN OF THE 180 KDA BULLOUS PEMPHIGOID ANTIGEN, BPAG2

IgA autoantibodies from the sera of some patients with linear IgA bull ous dermatosis (LABD) recognize a 97 kDa antigen (LABD97) located in t he lamina lucida of the basement membrane zone. As LABD autoantibodies do not react with the 180 and 230 kDa proteins recognized by bullous pemphigoid autoantibodies, LABD97 has been thought to represent a sepa rate lamina lucida protein. In this study, we purified LABD97 from the extract of human epidermis using a monoclonal antibody immunoaffinity column and analyzed the amino acid sequence of the N terminus of puri fied LABD97. This revealed a 16 amino acid sequence that was identical to a previously reported sequence of the 180 kDa antigen in bullous p emphigoid (BPAg2). The N terminus was located 41 amino acids downstrea m from the carboxyl end of the transmembrane domain of BPAg2 and 11 am ino acids downstream from the MCW-1 domain, the predominant bullous pe mphigold epitope. Purified LABD97 was subsequently enzymatically diges ted with endoproteinase Arg C and separated by chromatography, which r esulted in multiple peptide fractions. Fourteen of these fractions wer e subjected to amino acid sequencing. The amino acid sequence of the p eptide fractions, totaling 205 amino acids, were identical to sequence s contained within the extracellular domain of BPAg2. Whereas the pred ominant epitope identified with bullous pemphigoid sera is located in the noncollagenous region of this protein, the epitope recognized by L ABD sera is either within or adjacent to the collagenous portion. We c onclude that LABD97 represents a portion of the extracellular domain o f BPAg2 and that the IgA autoantibodies are directed against an epitop e within or adjacent to a collagenous domain.