Anti‐p200 pemphigoid: A novel autoimmune subepidermal blistering disease

Abstract

Anti-p200 pemphigoid is a recently defined autoimmune subepidermal blistering disease characterized by circulating and tissue-bound autoantibodies to a 200-kDa protein (p200) of the dermal-epidermal junction (DEJ). This DEJ constituent is thought to be important for adhesion of basal keratinocytes to the underlying dermis. While the exact identity of p200 remains unknown, it has been demonstrated to be immunologically and biochemically distinct from all major autoantigens of the DEJ, including bullous pemphigoid antigens 180 and 230, laminin 1, 5 and 6, alpha6beta4 integrin, and type VII collagen. Clinically, most reported cases present with tense blisters as well as urticarial papules and plaques, closely resembling bullous pemphigoid. Histopathological examination of lesional skin biopsies shows subepidermal split formation and superficial inflammatory infiltrate typically dominated by neutrophils. Immunopathologically, linear deposits of immunoglobulin (Ig)G and C3 are detected along the DEJ by direct immunofluorescence microscopy of perilesional skin. Indirect immunofluorescence microscopy of patients' sera on NaCl-split human skin demonstrates circulating IgG autoantibodies labeling the dermal side of the split. By immunoblotting, these autoantibodies recognize a 200-kDa protein of human dermis. Biochemical characterization of the p200 molecule revealed a noncollagenous N-glycosylated acidic protein with an isoelectric point of approximately 5.5. We present an overview of the pathogenesis, clinical features, diagnosis and treatment of this new disease entity.

From anti‐p200 pemphigoid to anti‐laminin γ1 pemphigoid

“…Typical epidermolysis bullosa acquisita patients also develop non-inflamed mechanical bullae that heal with atrophic scarring, although clinically indistinguishable from anti-laminin c1 pemphigoid or bullous pemphigoid in many cases. 5,9 Histologically, skin biopsy specimen from an early erythematous lesion show a linear infiltrate of neutrophils, and sometimes eosinophils, along the dermoepidermal junction, as discussed later. 5,9,10 Epidemiological accumulation We have diagnosed more than 70 cases of antilaminin c1 pemphigoid.…”

“…5,9 Histologically, skin biopsy specimen from an early erythematous lesion show a linear infiltrate of neutrophils, and sometimes eosinophils, along the dermoepidermal junction, as discussed later. 5,9,10 Epidemiological accumulation We have diagnosed more than 70 cases of antilaminin c1 pemphigoid. The number of cases is just half as many as the number of cases of epidermolysis bullosa acquisita, which we have definitely diagnosed by immunoblotting of human dermal extracts during the same time.…”

“…18 Indeed, in immunofluorescence on human skin sections, most patients' sera show no visible reactivity with blood vessel walls, except for a particular case. 5,6,9 We speculated the mechanism of this antigenic discrepancy among each organ as follows. The epitope of the autoantigen, suggested to be located at the C-terminus of laminin c1, may have a different 3-D structure in each laminin trimer among organs, or even in a posttranslational modification level of the single chain before folding.…”

“…Anti-laminin c1 pemphigoid has been at the head of the list. 5 This is a new autoimmune subepidermal bullous disease, which has been characterized by autoantibodies against a 200-kDa protein (p200) of the dermalepidermal junction. Despite attempts, the identity of p200 had remained an enigma.…”

Anti-laminin gamma-1 pemphigoid

“…Following our first cases described in 1996 (1, 2), more than 50 cases have been published (12). So far, the identity of the protein has remained an enigma.…”