Evidence for a role of autoantibodies to heat shock protein 60, 70, and 90 in patients with dermatitis herpetiformis

Cell Stress Chaperones. 2014 Nov;19(6):837-43. doi: 10.1007/s12192-014-0507-6. Epub 2014 Mar 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • Biomarkers / blood
  • Case-Control Studies
  • Celiac Disease / blood
  • Celiac Disease / diagnosis
  • Celiac Disease / diet therapy
  • Celiac Disease / immunology*
  • Chaperonin 60 / immunology*
  • Dermatitis Herpetiformis / blood
  • Dermatitis Herpetiformis / diagnosis
  • Dermatitis Herpetiformis / diet therapy
  • Dermatitis Herpetiformis / immunology*
  • Diet, Gluten-Free
  • Female
  • GTP-Binding Proteins
  • HSP70 Heat-Shock Proteins / immunology*
  • HSP90 Heat-Shock Proteins / immunology*
  • Humans
  • Immunity, Humoral
  • Male
  • Middle Aged
  • Mitochondrial Proteins / immunology*
  • Pemphigoid, Bullous / blood
  • Pemphigoid, Bullous / diagnosis
  • Pemphigoid, Bullous / immunology
  • Pemphigus / blood
  • Pemphigus / diagnosis
  • Pemphigus / immunology
  • Protein Glutamine gamma Glutamyltransferase 2
  • Time Factors
  • Transglutaminases / immunology

Substances

  • Autoantibodies
  • Biomarkers
  • Chaperonin 60
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • HSPD1 protein, human
  • Mitochondrial Proteins
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • transglutaminase 1
  • GTP-Binding Proteins