title: RasGAP-like protein IQGAP1 is expressed by human keratinocytes and recognized by autoantibodies in association with bullous skin disease.
abstract: Autoantibodies in patients with autoimmune bullous skin diseases, such as pemphigus or bullous pemphigoid are of diagnostic value and might play a part in the pathogenic scenario. In this study we present five patients with erythematous plaques, subepidermal blister formation of the skin, and the presence of circulating autoantibodies directed against a so far unrecognized 190 kDa antigen in human keratinocytes. Amino acid sequence analysis identified the protein as IQGAP1, a recently described human Ras GTPase-activating-like protein suspected to act as an effector molecule for Cdc42 and Rac1, members of the Rho small GTPase family and to play a key part in regulating E-cadherin-mediated cell adhesion. The protein is selectively recognized by a monoclonal anti-IQGAP1 antibody on western blots and immunoprecipitates from keratinocyte extracts. Indirect immunofluorescence locates IQGAP1 within individual keratinocytes in a cytoplasmic pattern and along the cell periphery at adhesive sites. Our results demonstrate IQGAP1, a newly described multifunctional protein, to be constitutively expressed in human keratinocytes where it may contribute to the integrity of the epidermal layer. Furthermore, we found autoantibodies reacting with IQGAP1 in patients with bullous skin eruptions most apparently belonging to the spectrum of bullous pemphigoid.
authors.affiliation: Department of Dermatology, Division of General Dermatology, University of Vienna, School of Medicine, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Presslauer
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hinterhuber
authors.forename: Karla
authors.initials: K
authors.lastname: Cauza
authors.forename: Reinhard
authors.initials: R
authors.lastname: Horvat
authors.forename: Klemens
authors.initials: K
authors.lastname: Rappersberger
authors.forename: Klaus
authors.initials: K
authors.lastname: Wolff
authors.forename: Dagmar
authors.initials: D
authors.lastname: Foedinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence / Q000235:genetics; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D004892:Erythema Multiforme / Q000276:immunology / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010391:Pemphigoid, Bullous / Q000276:immunology / Q000378:metabolism; D010392:Pemphigus / Q000276:immunology / Q000378:metabolism; D012016:Reference Values; D012867:Skin / Q000276:immunology; D012872:Skin Diseases, Vesiculobullous / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D020703:ras GTPase-Activating Proteins
chemical_list: D001323:Autoantibodies; D002352:Carrier Proteins; C101203:IQ motif containing GTPase activating protein 1; D020703:ras GTPase-Activating Proteins