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

Hardt-Weinelt, K.
Nilsson, H.
Wolter, Manfred
Dohlsten, M.
Ochsendorf, Falk Rudiger
Kaufmann, Roland
Antonsson, P.
Published in Journal of investigative dermatology. 2001, vol. 116, no. 4, p. 596-601
Abstract Psoriasis is a T-cell-mediated immune dermatosis probably triggered by bacterial superantigens. This pathomechanism has been experimentally reproduced in a SCID-hu xenogeneic transplantation model. We analyzed the effects of different 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 subfamily of staphylococcal enterotoxins only mimicked certain aspects of psoriasis. The biologic effects of staphylococcal enterotoxin A were more pronounced when a mutated form, SEA(H187A), of this superantigen with reduced affinity to major histocompatibility complex class II was coinjected. Another mutated variant, SEA(F47A/D227A), exhibiting no measurable major histocompatibility complex class II affinity blocked the effects triggered by wild-type staphylococcal enterotoxin A when injected in a 10-fold higher dose. Inhibition was specific as induction of psoriasiform epidermal changes by staphylococcal enterotoxin B could not be blocked. As staphylococcal enterotoxin A, in contrast to the other superantigens tested, is capable of inducing epidermal thickening but not the typical appearance of psoriasis, we conclude that bacterial superantigens may differ with regard to their effects on human nonlesional psoriatic skin. Staphylococcal-enterotoxin-A-mediated effects were blocked by a genetically engineered superantigen highlighting the potential therapeutic use of mutated superantigens.
Keywords AnimalsAntibody SpecificityBinding SitesEnterotoxins/*genetics/immunology/physiology/*therapeutic useHistocompatibility Antigens Class II/immunologyHumansMiceMice, SCID*MutationPsoriasis/*drug therapy*Skin TransplantationStaphylococcus/immunologySuperantigens/therapeutic use*Transplantation, Heterologous
PMID: 11286628
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BOEHNCKE, Wolf-Henning et al. Antagonistic effects of the staphylococcal enterotoxin a mutant, SEA(F47A/D227A), on psoriasis in the SCID-hu xenogeneic transplantation model. In: Journal of investigative dermatology, 2001, vol. 116, n° 4, p. 596-601. doi: 10.1046/j.1523-1747.2001.01295.x

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Deposited on : 2013-09-20

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