PMU-Autor/inn/en
Meyersburg DamianAbstract
The cell stress chaperone heat shock protein 90 (Hsp90) has been implicated in inflammatory responses and its inhibition has proven successful in different mouse models of autoimmune diseases, including epidermolysis bullosa acquisita. Here, we investigated expression levels and secretory responses of Hsp90 in patients with bullous pemphigoid (BP), the most common subepidermal autoimmune blistering skin disease. In comparison to healthy controls, the following observations were made: (i) Hsp90 was highly expressed in the skin of BP patients, whereas its serum levels were decreased and inversely associated with IgG autoantibody levels against the NC16A immunodominant region of the BP180 autoantigen, (ii) in contrast, neither aberrant levels of circulating Hsp90 nor any correlation of this protein with serum autoantibodies was found in a control cohort of autoimmune bullous disease patients with pemphigus vulgaris, (iii) Hsp90 was highly expressed in and restrictedly released from peripheral blood mononuclear cells of BP patients, and (iv) Hsp90 was potently induced in and restrictedly secreted from human keratinocyte (HaCaT) cells by BP serum and isolated anti-BP180 NC16A IgG autoantibodies, respectively. Our results reveal an upregulated Hsp90 expression at the site of inflammation and an autoantibody-mediated dysregulation of the intracellular and extracellular distribution of this chaperone in BP patients. These findings suggest that Hsp90 may play a pathophysiological role and represent a novel potential treatment target in BP.
Useful keywords (using NLM MeSH Indexing)
Aged
Aged, 80 and over
Autoantibodies/blood
Autoantibodies/immunology
Autoantigens/immunology
Cell Line
Cyclic AMP-Dependent Protein Kinases/metabolism
Epidermis/immunology
Epidermis/metabolism
Epidermis/pathology
Female
Gene Expression*
Glycoproteins/metabolism
HSP90 Heat-Shock Proteins/blood
HSP90 Heat-Shock Proteins/genetics*
HSP90 Heat-Shock Proteins/metabolism*
Humans
Immunoglobulin G/blood
Immunoglobulin G/immunology
Keratinocytes/immunology
Keratinocytes/metabolism
Leukocytes, Mononuclear/immunology
Leukocytes, Mononuclear/metabolism
Male
Middle Aged
Non-Fibrillar Collagens/immunology
Pemphigoid, Bullous/blood
Pemphigoid, Bullous/genetics*
Pemphigoid, Bullous/immunology
Pemphigoid, Bullous/metabolism*
Transforming Growth Factor alpha/metabolism