Abstract
Bullous pemphigoid (BP) is associated with autoantibodies to 230-kd and 160- to 180-kd hemidesmosomal antigens located in the most superficial layers of the basement membrane zone (BMZ). In this study, conducted to characterize BMZ antigens in different extracts of the skin, we unexpectedly found that some patients with BP also have antibodies to a 125-kd antigen present in the deep layers of the BMZ. By Western immunoblot analysis, antibodies that reacted strongly to a 125-kd antigen (BP125) in 4% sodium dodecyl sulfate plus 2 mol/L of urea extract of the dermal side of 1 mol/L of sodium chloride-split human skin were present in the serum samples of eight (21%) of 38 patients with BP, but in none of 55 control individuals (17 BMZ antibody-positive patients without BP and 38 BMZ antibody-negative patients). Immunofluorescence studies with affinity-purified antibody localized BP125 to the BMZ on the dermal side of the salt-split skin. BP125 was not detected in the epidermal portion of the salt-split skin, either by Western blot analysis of epidermal extracts or by indirect immunofluorescence with affinity-purified antibody, indicating it is not an epidermal antigen that contaminates the dermis during the salt-splitting procedure, and which argues against it being a breakdown product of the 230-kd or 160- to 180-kd BP antigens. These results indicate that autoantibodies in BP can be directed to different antigens present in different strata within the BMZ and suggest that different immune mechanisms may be involved in the pathogenesis of this disease.
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