Antagonistic effects of the staphylococcal enterotoxin a mutant, SEA(F47A/D227A), on psoriasis in the SCID-hu xenogeneic transplantation model

Citation
Wh. Boehncke et al., Antagonistic effects of the staphylococcal enterotoxin a mutant, SEA(F47A/D227A), on psoriasis in the SCID-hu xenogeneic transplantation model, J INVES DER, 116(4), 2001, pp. 596-601
Citations number
32
Categorie Soggetti
Dermatology,"da verificare
Journal title
JOURNAL OF INVESTIGATIVE DERMATOLOGY
ISSN journal
0022202X → ACNP
Volume
116
Issue
4
Year of publication
2001
Pages
596 - 601
Database
ISI
SICI code
0022-202X(200104)116:4<596:AEOTSE>2.0.ZU;2-U
Abstract
Psoriasis is a T-cell-mediated immune dermatosis probably triggered by bact erial superantigens, This pathomechanism has been experimentally reproduced in SCID-hu xenogeneic transplantation model. We analyzed the effects of di fferent bacterial superantigens on the induction of psoriasis in this model , Staphylococcal enterotoxin B and exfoliative toxin triggered the onset of psoriasis when administered repetitively intracutaneously over a period of 2 wk, whereas staphylococcal enterotoxin A representing a distinct subfami ly of staphylococcal enterotoxins only mimicked certain aspects of psoriasi s, The biologic effects of staphylococcal enterotoxin A were more pronounce d when a mutated form, SEA(H187A), of this superantigen with reduced affini ty to major histocompatibility complex class II was coinjected, Another mut ated variant, SEA(F47A/D227A), exhibiting no measurable major histocompatib ility complex class II affinity blocked the effects triggered by wildtype s taphylococcal enterotoxin A when injected in a 10-fold higher dose. Inhibit ion was specific as induction of psoriasiform epidermal changes by staphylo coccal enterotoxin B could not be blocked. As staphylococcal enterotoxin A, in contrast to the other superantigens tested, is capable of inducing epid ermal thickening but not the typical appearance of psoriasis, we conclude t hat bacterial superantigens may differ with regard to their effects on huma n nonlesional psoriatic skin. Staphylococcal-enterotoxin-A-mediated effects were blocked by a genetically engineered superantigen highlighting the pot ential therapeutic use of mutated superantigens.