The localization of the target antigens and antibodies in linear IgA disease is heterogeneous, and dependent on the methods used

Summary Fifty‐nine patients with linear IgA disease, 24 with onset in childhood and 35 with adult onset, were studied. Sera from all patients were tested by indirect immunofluorescence, using as substrates intact normal skin and normal skin which had been split through the lamina lucida region of the basement membrane zone by suction and by prolonged incubation with molar NaCl. This enabled the site of the target antigen for the circulating IgA antibodies to be determined. The sites of deposition of the IgA antibodies in vivo were detected by raising a suction blister in eight patients, and splitting seven patients’ biopsies by prolonged incubation with molar NaCl. Eighteen sera were positive with intact skin, and 34 with split skin. Twenty‐nine sera were positive with suction blisters as substrate; 14 bound to the epidermal aspect of the split skin, seven in a combined pattern (binding to the epidermis and dermis) and six to the dermal aspect. Thirty‐one sera bound to salt‐split skin, 24 to the epidermal side and seven on the dermal side. There was discordance between the two methods of skin splitting in 15 sera. Seven sera gave a combined pattern with suction but with salt‐split skin, five of these bound epidermally, one was dermal, and one negative. Five sera showed epidermal binding on saltsplit skin and were negative on suction blisters, and the reverse was seen with one serum. Two sera gave variable results on suction blisters. Direct immunofluorescence studies showed dermal binding on all eight patients with suction blisters, and epidermal binding in four and dermal binding in three patients with salt splitting. These results demonstrate that the location of the target antigens and the sites of deposition of the antibodies are dependent on the methods used. They also suggest that there are at least two different antigens, an epidermal‐ and a dermal‐associated antigen. The sera reacting in the combined pattern may represent antibodies reacting with a different epitope of the epidermal antigen, with a further epidermal antigen, or with two target antigens.