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
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.