A comparison of the expression of known basement membrane components with the linear IgA disease antigens using the novel substrate cylindroma

Linear IgA disease (LAD) is characterized by IgA basement membrane zone aut oantibodies. Immunofluorescence, immunoblotting and immunoelectron microsco py studies have established the complexity and heterogeneity of the target antigens. We have studied the expression of the LAD antigens by cylindroma, a benign epithelial tumour that secretes abundant basement membrane, using 57 LAD sera categorized by indirect immunofluorescence on intact and salt- split skin. The expression of known components of hemidesmosomes, the ancho ring filaments, extracellular matrix and the anchoring fibrils could be dif ferentiated and were compared with the expression of the LAD antigene. The results showed that the LAD sera bound to the cylindroma tumour in two dist inctive patterns. Thirty-three sera were positive on cylindroma. Twenty-sev en sera bound to the basement membrane around the tumour clusters and the i slets within the clusters in a thin linear band that was occasionally disco ntinuous. This was similar to the pattern observed with antibodies to the h emidesmosome components, the alpha 6 beta 4 integrin and the bullous pemphi goid antigens BP230 and BP180. This pattern was observed with sera that bou nd to the epidermal (11) and the dermal () aspects of split skin or were ne gative (11), and with one serum which bound only to intact skin. Seven sera , all binding to the dermal aspect of split skin, bound the tumour cluster basement membrane in a thick band that was identical in appearance to that seen with antibodies to collagen VII; however, binding to the islets was ei ther identical to collagen VII or similar but differentiated with double st aining. Some sera were negative on cylindroma. Using fluorescence overlay a ntigen mapping we demonstrated colocalization of some epidermal-associated LAD target antigens with known hemidesmosome proteins, and colocalization o f some dermal-associated LAD target antigens with anchoring fibril componen ts. The results using cylindroma as substrate suggest that LAD autoantibodi es may react with three or more target antigens. We propose from the result s of this study that the autoantibodies in LAD target multiple antigens ass ociated with hemidesmosomes and anchoring fibrils.