Bullous pemphigoid: end of the century overview.

Abstract

Bullous pemphigoid (BP) was first described by Lever in 1953 as a subepidermal blistering disease. Immunohistological features of BP include dermal-epidermal junction separation with an inflammatory cell infiltrate in the upper dermis, and autoantibodies in patients' circulation and bound to the basement membrane zone (BMZ). These autoantibodies show a linear staining at the dermal-epidermal junction (DEJ) and recognize two major hemidesmosomal proteins, the BP230 (BPAG1) and BP180 (BPAG2). An IgG passive transfer mouse model of BP was developed, that recapitulates the key features of human BP. Using this in vivo model system, key cellular and molecular events leading to BP disease phenotype are identified, including IgG binding to its target, complement activation, mast cell degranulation, neutrophil infiltration and activation. Proteinases and reactive oxygen species released by neutrophils work together to damage BMZ, causing DEJ separation. T cells from BP patients show a specific proliferative response to recombinant BP180 NC16A. These NC16A-responding T lymphocytes express alpha/beta T cell receptors and CD4 memory T cell surface markers and exhibited a Th1/Th2 mixed cytokine profile. After almost a half-century of studies, we have learned a great deal about IgG-mediated tissue injury and begin to understand the autoimmune responses leading to pathogenic IgG production in BP.