Laminin 332 in Junctional Epidermolysis and as an Autoantigen in Mucous Membrane Pemphigoid

Abstract

Laminin 332, with chain composition I3, I3, I2, is a component of basement membranes localised beneath specialised epithelia with secretory or protective function. This protein plays a pivotal structural role as it directly connects basal epithelial cells to the underlying extracellular matrix molecular networks. Its deficiency in human inherited and autoimmune disorders has emphasised the importance of laminin 332 for the structural integrity of the dermal epidermal junction in skin. The junctional form of epidermolysis bullosa, a skin disease characterised by loss of cohesion between the epidermis and the dermis that results in blister formation and chronic wounds, is caused by genetic mutations in several different genes encoding proteins of the epidermal adhesion complex such as the three chains of laminin 332. Besides, autoimmune disorders affecting laminin 332 belong to the mucous membrane pemphigoid heterogeneous group of rare autoimmune blistering diseases. Anti-laminin 332 autoantibodies cause erosive lesions followed by scarring of the skin and mucous membranes. This chapter reviews the molecular characteristics of laminin 332, its organisation within basement membranes and its involvement in bullous diseases.