Matrix Metalloproteinases and Autoimmune Bulbous Diseases: Expression of MMP-2, -3, and -9 in Bullous Pemphigoid, Pemphigus Vulgaris, and Pemphigus Foliaceus

Chun, Ji Sun; Yun, Sook Jung; Kim, Seong Jin; Lee, Seung Chul; Won, Young Ho; Lee, Jee Bum

Abstract

BACKGROUND
Matrix metalloproteinases (MMPs) participate in extracellular matrix degradation and may play an important role in basal membrane damage in many dermatologic diseases. Recent studies implicated the importance of MMP-9 in the pathogenesis of bulla formation of bullous pemphigoid (BP). Various autoimmune bullous diseases are strongly associated with desmosome or hemidesmosome pathologies, and show an increased level of lesional MMP and exposed autoantigens from these structures.
OBJECTIVE
This study evaluated the level of MMP-2, -3, and -9 in three types of autoimmune bullous disease [BP, pemphigus vulgaris (PV), pemphigus foliaceus (PF)] with the aim of investigating the role of MMPs in the pathogenesis of autoimmune bullous diseases.
METHODS
Sample specimens were obtained from skin lesions of patients with BP (n=12), PV (n=10), and PF (n=12), and from normal controls (n=8). The immunohistochemical expression of MMP-2, -3, and -9 was analyzed and serum levels of MMP-2, -3, and -9 were measured by enzyme-linked immunosorbant assay (ELISA). The results were analyzed with reference to graded levels of clinical severity.
RESULTS
Expression of dermal MMP-2, -3, and -9 were increased in BP, PV, and PF (p=0.036, 0.022, and 0.015, respectively). However, decreased expression of the three MMPs in the epidermis of skin lesions may have resulted from epidermal destruction. ELISA-determined serum levels of MMP-2, -3, and -9 increased in BP, PV and PF. Interestingly, MMP-2 was significantly increased in the sera of BP patients (p=0.015), consistent with the previous studies concerning the role of gelatinase (MMP-2 and -9) in the pathogenesis of BP. In BP patients, clinical severity was proportional to increased levels of MMP-2 in both skin lesions and and sera.
CONCLUSION
The increased expression of MMP-2, -3, and -9 in skin lesions and sera may reflect the involvement of these enzymes in the mechanism of bulla formation in autoimmune bullous diseases including BP. In addition, expression of MMP and clinical severity may be closely connected.