Molecular Overlap of the IgA Target Antigens in the Subepidermal Blistering Diseases

Abstract

Linear IgA disease (LAD) has circulating IgA auto-antibodies which have been found to be associated with epidermal- and dermal-derived antigens. The localization and molecular weight(s) of the IgA target antigen(s) implicated in LAD and their relationship to the target antigens for the IgA antibodies in bullous pemphigoid (BP) and cicatricial pemphigoid (CP) are unknown. Sera from patients with all 3 diseases who had circulating IgA antibodies were studied by immunoblotting with both epidermal and dermal extracts. Our findings indicate that there is heterogeneity in the localization and molecular weights of the target antigen(s), with multiple bands demonstrated with some sera. Three principal target antigens were identified with molecular weights of 110–120, 160–180 and one approximately 285 kD. These antigens were common to all 3 diseases and were found in 25 patients. These results suggest that the target antigens for IgA basement membrane zone antibodies in LAD, BP and CP are multiple, complex in composition and may differ from the conventional BP antigens.

The localization of target antigens and autoantibodies in linear IgA disease is variable: correlation of immunogold electron microscopy and immunoblotting

“…5,7,9,11,12 We found the LAD antigen, LAD285, which we have previously described, in addition, in one of these sera. Five patients had autoantibodies reacting with more than one antigen or epitope.…”

“…4,5 One patient also had autoantibodies to an epidermal protein of 200 kDa: this has not previously been described in LAD. 4,5,28 The autoantibodies present in the purified blister fluid gave a similar labelling pattern to that of the MoAb LH7.2 to collagen VII (Fig. 18 All the autoantibodies binding to the hemidesmosome or lamina lucida recognized proteins in epidermal extracts of molecular weight 180 kDa (or its breakdown product of 97 kDa), 200 kDa or 230 kDa.…”

“…A protein of molecular weight 180 kDa, presumably BP180, was the most frequently recognized antigen, in five of six patients, three of whom also reacted with the 97 kDa protein, now considered to be a breakdown the literature. The presence of autoantibodies to BP180 (or 97 kDa) in LAD is now well recognized, 5,7,11 and this pattern may be compatible with the transmembrane region of this molecule. 4,5 One patient also had autoantibodies to an epidermal protein of 200 kDa: this has not previously been described in LAD.…”

Linear IgA Bullous Disease Presenting as Toxic Epidermal Necrolysis: A Case Report and Review of the Literature

“…Several of the target antigens involved in the pathogenesis of LABD have been identified: 97-kDa, 120-kDa antigens, BP180, and BP230 [1,25,26,27,28]. Both the 97-kDa and 120-kDa antigens are proteolytic cleavage products of the BP180 ectodomain [29,30].…”

Linear IgA Disease: Cylindroma Demonstrates Heterogeneity of the Target Antigens

“…It is characterized by linear IgA deposition at the basement membrane zone (BMZ) and in some cases by circulating IgA auto-antibodies to the BMZ [1], There is evidence from split skin studies [2,3] and immuno-electron microscopy studies [4][5][6][7] of at least 2 target antigens, one an epidermal associated, lamina lucida antigen and the other associated with the dermal side of split skin and below the lamina densa. Immunoblotting has not resolved the controversy but has suggested that some of the antigens are unique to LAD [18][19][20], Cylindroma is an appendageal tumour thought to origi nate from sweat duct epithelium and which may be inher ited in an autosomal dominant fashion as either single or multiple tumours [21]. Cylindromas produce an excess of BMZ components including laminin, and collagens IV and VII [22][23][24][25], We present here in brief the results of our studies on sera from 58 LAD patients using the novel substrate cylin droma.…”