Gelatinases A and B are expressed in late lesions in autoimmune bullous disorders

Gelatinases (or metalloproteinase or collagenases) are involved in remodelling the extracellular matrix in several skin disorders. Previous reports show that the 72 kDa (Gelatinase A), the 92 kDa collagenase (Gelatinase B) and their inhibitors TIMP-2 and TIMP-1 respectively are overexpressed in tumor invasion and metastasis, granuloma annulare, necrobiosis lipoidica diabeticorum and bullous pemphigoid. Usually their natural inhibitors, TIMP-1 and TIMP-2, are inversely related to the production of the 72 kDa and 92 kDa proteins. 8 patients affected by Bullous Pemphigoid (BP) and 8 patients affected by Pemphigus Vulgaris (PV) were biopsized in perilesional areas of young lesions and in lesional areas of old lesions. Materials were snap frozen in liquid nitrogen until use. Antibodies to 72 kDa, 92 kDa, TIMP-1, TIMP-2, CD44, laminin, collagen type I, III, IV, VII were used and evidentiated by the avidin-biotin immunoperoxidase technique. mRNA expression for Gelatinases and their inhibitors were also analyzed by RT-PCR. In all patients we found gelatinases expression only in the late lesions. A different expression was found between the two diseases, the 92 kDa protein and its inhibitor TIMP-1 were positive in both PB and PV whereas the 72 kDa form and its inhibitor TIMP-2 were evident only in PB. By RT-PCR we show that the 72 kDa mRNA was expressed exclusively in the dermis, on the contrary the 92 kDa was present in epidermis and dermis. No signals were detected in the early phase of blistering suggesting a role of gelatinases in re-epithelization but not in blistering where other proteases play a major role. The differential expression of Gelatinases and their inhibitors is probably under a cytokine network control.