Abstract
Objective
To investigate the role of the novel cytokine high mobility group box chromosomal protein 1 (HMGB‐1) in the pathogenesis of cutaneous lupus erythematosus (CLE).
Methods
Punch biopsy specimens of lesional and unaffected skin from 10 patients with CLE and 3 healthy control subjects were investigated. Immunohistochemical staining for HMGB‐1, tumor necrosis factor α (TNFα), and interleukin‐1β (IL‐1β) was performed on consecutive sections. Analysis of single‐nucleotide polymorphisms of −308 TNF was performed on DNA extracted from peripheral blood mononuclear cells.
Results
An altered expression of HMGB‐1 was observed both in the epidermis and in the dermal infiltrates of lesional skin. Expression of HMGB‐1 in the epidermis and dermis was increased (P < 0.01 and P < 0.001, respectively, versus unaffected skin), and translocation to the cytoplasm as well as the extracellular presence of secreted HMGB‐1 were found. Increased levels of TNFα and IL‐1β were also observed in the dermal infiltrates of lesional skin (P < 0.01 and P < 0.05, respectively, versus unaffected skin). The carrier frequency of the −308A TNF polymorphism was 80% in patients with subacute CLE, but this was not related to higher expression of TNFα in biopsy specimens from the CLE group.
Conclusion
The high amount of extracellular HMGB‐1 observed in skin lesions indicates that HMGB‐1 is involved in the inflammatory process of CLE. TNFα and IL‐1β may form a proinflammatory loop with HMGB‐1, since they can induce the release of each other. The extracellular HMGB‐1 observed by immunostaining of the epidermis indicates that keratinocytes may be an as yet unrecognized source of secreted HMGB‐1, underscoring the role of the target organ in the rheumatoid autoimmune inflammatory process.