title: Altered distribution of keratinization markers in epidermolytic hyperkeratosis.
abstract: Epidermolytic hyperkeratosis (EH) is a genetic disorder of keratins associated with epidermal differentiation. Affected individuals carry gene mutations for conserved sequences of keratins K1 or K10. The structural alterations of tonofilaments in EH seem to be a direct consequence of the keratin gene mutations. EH epidermis, however, shows many other unexplained abnormalities including acanthosis, hypergranulosis, and hyperkeratosis. To further elucidate the pathogenetic mechanism of EH, we studied distribution patterns of other keratinization-associated molecules including involucrin, small proline-rich protein (SPRR) 1, loricrin and trichohyalin in the skin of four patients by light and electron microscopic immunohistochemistry in conjunction with conventional transmission electron microscopy. The middle to upper epidermal cells showed moderate to strong immunoreactivities to involucrin, SPRR1 and loricrin antibodies. Both intracellular staining and cell peripheral staining was seen for involucrin and SPRR1 antibodies. Loricrin labelling was prematurely associated with the plasma membrane of granular cells, possibly relating to abnormal keratin filament aggregation and cellular vacuolization. Some loricrin labelling was localized on the keratin aggregates, suggesting intermolecular associations between keratin and loricrin. Trichohyalin, hardly detectable in normal epidermis, was present in some granular and cornified cells in EH in association with keratin filaments, suggesting that it may function as an intermediate filament-associated protein. While cornified cell envelopes were intensely labelled only with loricrin antibodies in normal skin, they were immunoreactive to involucrin, SPRR1 and loricrin antibodies in EH. Sequential change in electron density of the cornified cell envelopes, a constant feature in normal skin, was often absent in EH. These results suggest an altered assembly process of cornified cell envelopes in EH.
authors.affiliation: Department of Cell Pathology, St. John's Institute of Dermatology, St. Thomas's Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Ishida-Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Iizuka
authors.forename: M
authors.initials: M
authors.lastname: Manabe
authors.forename: W M
authors.initials: WM
authors.lastname: O'Guin
authors.forename: D
authors.initials: D
authors.lastname: Hohl
authors.forename: T
authors.initials: T
authors.lastname: Kartasova
authors.forename: T
authors.initials: T
authors.lastname: Kuroki
authors.forename: D R
authors.initials: DR
authors.lastname: Roop
authors.forename: R A
authors.initials: RA
authors.lastname: Eady
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D055233:Cornified Envelope Proline-Rich Proteins; D005260:Female; D006801:Humans; D017488:Hyperkeratosis, Epidermolytic / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D007381:Intermediate Filament Proteins; D007633:Keratins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D011498:Protein Precursors / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013194:Staining and Labeling; D014018:Tissue Distribution
chemical_list: D015415:Biomarkers; D055233:Cornified Envelope Proline-Rich Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; D011506:Proteins; C064554:loricrin; C016159:trichohyalin; D007633:Keratins