title: Evidence for a role of autoantibodies to heat shock protein 60, 70, and 90 in patients with dermatitis herpetiformis.
abstract: Heat shock proteins (Hsp) are highly conserved immunomodulatory molecules upregulated when cells are exposed to stressful stimuli, such as inflammation. Their involvement in various autoimmune diseases, including autoimmune bullous diseases and celiac disease, has been increasingly recognized. To further study the role of Hsp in autoimmune bullous diseases, we have investigated for the first time the humoral autoimmune response to Hsp40, Hsp60, Hsp70, and Hsp90 in patients with dermatitis herpetiformis (DH; n = 26), bullous pemphigoid (BP; n = 23), and pemphigus vulgaris (PV; n = 16), the first representing a cutaneous manifestation of celiac disease. While in patients with active BP and PV, serum levels of autoantibodies against these Hsp did not differ from the corresponding age- and gender-matched healthy controls (n = 9-14); circulating autoantibodies against Hsp60, Hsp70, and Hsp90 were found to be increased at the active disease stage of DH. Further analysis of this latter patient subgroup showed that these anti-Hsp autoantibodies decreased in parallel with serum autoantibodies against epidermal and tissue transglutaminase during remission of skin lesions following a gluten-free diet, revealing significantly positive correlations. Although further studies on larger groups of patients will be needed to confirm the present data, our results support the notion that autoantibodies against Hsp60, Hsp70, and Hsp90 deserve attention in the study of the mechanisms that promote the development and maintenance of DH and possibly also the underlying celiac disease as well as potential novel disease biomarkers.
authors.affiliation: Department of Dermatology, University of Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany, Michael.Kasperkiewicz@uk-sh.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Kasperkiewicz
authors.forename: Stefan
authors.initials: S
authors.lastname: Tukaj
authors.forename: Anna-Julia
authors.initials: AJ
authors.lastname: Gembicki
authors.forename: Pálma
authors.initials: P
authors.lastname: Silló
authors.forename: Anna
authors.initials: A
authors.lastname: Görög
authors.forename: Detlef
authors.initials: D
authors.lastname: Zillikens
authors.forename: Sarolta
authors.initials: S
authors.lastname: Kárpáti
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002446:Celiac Disease / Q000097:blood / Q000175:diagnosis / Q000178:diet therapy / Q000276:immunology*; D018834:Chaperonin 60 / Q000276:immunology*; D003874:Dermatitis Herpetiformis / Q000097:blood / Q000175:diagnosis / Q000178:diet therapy / Q000276:immunology*; D055050:Diet, Gluten-Free; D005260:Female; D019204:GTP-Binding Proteins; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000276:immunology*; D010391:Pemphigoid, Bullous / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D010392:Pemphigus / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D013997:Time Factors; D011503:Transglutaminases / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C060293:HSPD1 protein, human; D024101:Mitochondrial Proteins; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; C105804:transglutaminase 1; D019204:GTP-Binding Proteins