title: Immunohistochemical analysis of the skin in junctional epidermolysis bullosa using laminin 5 chain specific antibodies is of limited value in predicting the underlying gene mutation.
abstract: The anchoring filament protein laminin 5 is composed of three polypeptide chains (alpha 3, beta 3 and gamma 2) each encoded by separate genes (LAMA3, LAMB3 and LAMC2, respectively). Mutations in any of these three genes may give rise to the autosomal recessive blistering skin disease, junctional epidermolysis bullosa. At present, there is no easy way of predicting which of these three genes might harbour the pathogenetic laminin 5 mutations in a case of junctional epidermolysis bullosa. In this study, we assessed whether immunohistochemistry might be helpful in this regard. We performed immunohistochemical labelling of the dermal-epidermal junction using alpha 3, beta 3 and gamma 2 chain-specific antibodies in 11 patients with junctional epidermolysis bullosa, in whom the laminin 5 mutations had been previously delineated. Although, labelling for the laminin 5 chain bearing the mutations was attenuated or undetectable in all cases, a complete absence of labelling or a reduction in the staining intensity for the other two chains was also seen in all cases. The results showed that immunohistochemical labelling of the dermal-epidermal junction using alpha 3, beta 3 and gamma 2 chain-specific antibodies is not a specific indicator for which of the laminin 5 chain genes contains the pathogenetic mutations, and is therefore unreliable in screening for individual laminin 5 gene mutations in cases of junctional epidermolysis bullosa.
authors.affiliation: St John's Institute of Dermatology (UMDS), St Thomas' Hospital, London, U.K.
authors.forename: J R
authors.initials: JR
authors.lastname: McMillan
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
authors.forename: L
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: A
authors.initials: A
authors.lastname: Kon
authors.forename: R E
authors.initials: RE
authors.lastname: Burgeson
authors.forename: J P
authors.initials: JP
authors.lastname: Ortonne
authors.forename: G
authors.initials: G
authors.lastname: Meneguzzi
authors.forename: J
authors.initials: J
authors.lastname: Uitto
authors.forename: R A
authors.initials: RA
authors.lastname: Eady
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics*; D005804:Genes, Lethal; D005808:Genes, Recessive; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009154:Mutation; D012867:Skin / Q000737:chemistry* / Q000196:embryology; D000097794:Kalinin
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D000097794:Kalinin