Disturbances of the expression of metalloproteinases and their tissue inhibitors cause destruction of the basement membrane in pemphigoid.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease which pathogenesis is associated with destruction of the basement membrane components and the anchoring fibers. The binding of autoantibodies to antigens localized in the basement membrane of the epidermis activates a series of immunological and enzymatic phenomena that lead to blister formation. There are some data that MMPs are involved in the development of skin lesions in BP, however their exact role in this process is not fully understood. We aimed to investigate whether MMPs and their inhibitors (TIMPs), assessed by their tissue expression, are involved in the pathogenesis of BP. The localization and expression of collagenase (MMP1), gelatinase (MMP2), 92 kD gelatinase (MMP9) and stromelysin 2 (MMP10) and TIMP1, 2, 3 were examined by immunohistochemistry in skin biopsies as well as in normal human skin specimens. The study included 21 patients with BP at an active stage of the disease. The MMPs and TIMPs serum levels were measured by ELISA method. Expression of MMP1, MMP2, MMP9 and MMP10 was observed either in the whole epidermis or in the basal keratinocytes. Most of the enzymes examined, apart from TIMP3, were detected in dermal part of the blister. Expression of the majority of the enzymes examined was observed in blister fluid however, the most intense signal was noted for MMP10. In cellular infiltrate we found expression of all the MMPs and TIMPs, the most distinct for MMP1, MMP2, MMP10 and for TIMP2. In all biopsies obtained from healthy volunteers only single basal keratinocytes gave positive, weak signal for the examined proteins. The MMPs and TIMPs serum levels in the control group were normal while in some cases of BP patients they were increased. Based on the results we conclude that imbalance between these enzymes really occurs in BP and it is likely to take important part in the pathogenesis of the disease.