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Reactivity of autoantibodies from patients with defined subepidermal bullous diseases against 1 mol/L salt-split skin. Specificity, sensitivity, and practical considerations.

BACKGROUND: Circulating IgG anti-basement membrane autoantibodies from patients with subepidermal bullous diseases can be categorized on the basis of their pattern of reactivity against 1 mol/L sodium chloride (NaCl)-split skin.

OBJECTIVE: The purpose of this study was to define by immunochemical techniques the specific antigen(s) targeted by IgG autoantibodies from a group of patients with subepidermal blistering diseases and then (1) prospectively determine which side(s) of 1 mol/L NaCl-split skin is (are) bound by these patients' autoantibodies, (2) compare the sensitivity of intact and 1 mol/L NaCl-split skin for the detection of these autoantibodies; and (3) devise a practical method to distinguish patients with antiepiligrin cicatricial pemphigoid from those with other subepidermal blistering diseases.

METHODS: Investigative techniques included direct and indirect immunofluorescence microscopy, immunoprecipitation studies, and immunoblotting.

RESULTS: These studies identified 14 patients whose sera immunoprecipitate bullous pemphigoid antigens 1, 2, or both. These patients' circulating IgG anti-basement membrane autoantibodies bind the epidermal (n = 11), epidermal and dermal (n = 2), or dermal (n = 1) sides of 1 mol/L NaCl-split skin by indirect immunofluorescence microscopy. In contrast, IgG from all patients with autoantibodies directed against type VII collagen (n = 5) or epiligrin (n = 6) bind only the dermal side of 1 mol/L NaCl-split skin. In all but one patient in this series, 1 mol/L NaCl-split skin proved to be a more sensitive test substrate than intact human skin for detection of circulating IgG anti-basement membrane autoantibodies. Patients with antiepiligrin cicatricial pemphigoid were distinguished from other patients in that their circulating autoantibodies bound epidermal basement membrane in the skin of primates but not small mammals.

CONCLUSION: NaCl-split skin (1 mol/L) of various species is a sensitive and practical indirect immunofluorescence microscopy test substrate for the evaluation of patients with IgG anti-basement membrane autoantibodies and evaluation of subepidermal bullous diseases.

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