Bullous pemphigoid: simple measures for a complex disease.
ABSTRACT Simple descriptive population data are potentially helpful in understanding how bullous pemphigoid (BP) originates and evolves over time. Before embarking with etiological correlations, artifacts and biases should be ruled out. Ideally, epidemiological data should be complemented by immunological and genetic analyses aimed at providing better insight into the causation and prognosis of BP.
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ABSTRACT: Bullous pemphigoid antigen 1 (BPAG1) is a member of the plakin family with cytoskeletal linker properties. Mutations in BPAG1 cause sensory neuron degeneration and skin fragility in mice. We have analyzed the BPAG1 locus in detail and found that it encodes different interaction domains that are combined in tissue-specific manners. These domains include an actin-binding domain (ABD), a plakin domain, a coiled coil (CC) rod domain, two different potential intermediate filament-binding domains (IFBDs), a spectrin repeat (SR)-containing rod domain, and a microtubule-binding domain (MTBD). There are at least three major forms of BPAG1: BPAG1-e (302 kD), BPAG1-a (615 kD), and BPAG1-b (834 kD). BPAG1-e has been described previously and consists of the plakin domain, the CC rod domain, and the first IFBD. It is the primary epidermal BPAG1 isoform, and its absence that is the likely cause of skin fragility in mutant mice. BPAG1-a is the major isoform in the nervous system and a homologue of the microtubule actin cross-linking factor, MACF. BPAG1-a is composed of the ABD, the plakin domain, the SR-containing rod domain, and the MTBD. The absence of BPAG1-a is the likely cause of sensory neurodegeneration in mutant mice. BPAG1-b is highly expressed in muscles, and has extra exons encoding a second IFBD between the plakin and SR-containing rod domains of BPAG1-a.The Journal of Cell Biology 09/2001; 154(4):691-7. · 10.82 Impact Factor
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ABSTRACT: The simultaneous occurrence of bullous pemphigoid (BP) and multiple sclerosis (MS), two autoimmune diseases involving the skin and the central nervous system (CNS), respectively, has been described. As the BPAG1 gene encodes the epithelial isoform of BP antigen 1 (BPAG1-e), a major autoantigen of BP, as well as additional variants expressed in the neurones of the CNS and peripheral nervous system and in Schwann cells, we tested the hypothesis that products of the BPAG1 gene act as shared autoantigens in both BP and MS. The reactivity of cerebrospinal fluid (CSF) obtained from 18 patients with MS, 10 patients with other inflammatory CNS diseases and 20 normal controls was assayed by immunoblotting against two recombinant fragments of BPAG1-e encompassing regions that are also found in the neuronal variants BPAG1-n and BPAG1-a. The recombinant protein glutathione-S-transferase (GST)-BPAG1-e1-887 was recognized by five of 18 (27%) CSF samples obtained from patients with MS, two of 10 (20%) samples from patients with other inflammatory neurological diseases and five of 20 (25%) samples from normal controls. Furthermore, two of 18 (11%) CSF samples from patients with MS bound to GST-BPAG1-e1880-2649, whereas none of the samples obtained from patients with other inflammatory neurological diseases or from control subjects showed reactivity. These results raise the possibility that a subset of patients with MS develops an autoantibody response to the neuronal variants of BPAG1. These findings potentially open the avenue of neuronal BPAG1 variants being novel targets of autoantibodies in neurological diseases.British Journal of Dermatology 04/2005; 152(3):537-40. · 3.76 Impact Factor
Article: What's the denominator?The Lancet 08/1993; 342(8863):97-9. · 39.06 Impact Factor