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Keywords:

  • autoantibodies;
  • periplakin;
  • toxic epidermal necrolysis

Summary

Background  The pathophysiological mechanism of toxic epidermal necrolysis (TEN) with extensive bullae that is induced suddenly by drugs is not well understood. The individual patterns and distribution of the widespread mucocutaneous reactions of TEN often show striking similarities with those of paraneoplastic pemphigus (PNP), which is known to involve autoantibodies (aAbs) to members of the plakin family.

Objectives  To investigate the existence of circulating aAbs to periplakin in the sera of patients with TEN.

Methods  The presence of circulating aAbs to periplakin was examined using immunoblotting, immunoabsorption and indirect immunofluorescence (IF) analyses. Recombinant protein expression was used to determine the interaction between periplakin and aAbs in the sera of patients with TEN.

Results  Indirect IF studies revealed circulating aAbs in the intercellular area in the epidermis. Interestingly, on rat bladder the staining pattern of the IgG deposits was similar to that observed in patients with PNP. Immunoblotting analysis of the epidermal extracts was used to identify the aAbs in the sera of patients with TEN. These contained circulating aAbs to a 190-kDa protein corresponding to periplakin. Recombinant periplakin and domains of periplakin were prepared in order to confirm the existence of aAbs to periplakin. Immunoblotting with these proteins demonstrated that the sera from patients with TEN reacted with each domain as well as with the full-length periplakin.

Conclusions  We found that circulating aAbs in the sera of patients with TEN target periplakin. These aAbs might play a role in the pathogenesis of TEN as a humoral autoimmune mechanism.