title: The role of immune response to Staphylococcus aureus superantigens and disease severity in relation to the sensitivity to tacrolimus in atopic dermatitis.
abstract: BACKGROUND
  Staphylococcus aureus-producing superantigens (SAgs), such as staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin-1 (TSST-1), are frequently observed in atopic dermatitis (AD). However, little has been done to establish the association of immune responses to SAgs and the therapeutic response to immunosuppressive drugs in AD. Therefore, we investigated the prevalence and role of SAgs in the pathophysiology and immunosuppressive drug sensitivity in AD patients.
  
  
  METHODS
  We classified 29 patients into two groups on the basis of their clinical AD scores: a low-score group (n = 14) corresponding to mild to moderate patients and a high-score group (n = 15) corresponding to severe patients. We estimated the plasma anti-SEB or TSST-1 IgE of these patients and healthy subjects by ELISA. We also estimated individual drug sensitivity by determining drug concentrations that would give 50% inhibition (IC(50)) of peripheral-blood mononuclear cell (PBMC) proliferation in vitro.
  
  
  RESULTS
  The levels of plasma anti-SEB or TSST-1 IgE in the severe patients were significantly higher than those in the mild to moderate patients (p < 0.05 and p < 0.01, respectively). When stimulated with concanavalin A in vitro, PBMCs in the severe patients exhibited low sensitivity to the suppressive efficacy of tacrolimus (FK506) as compared to the mild to moderate patients (p < 0.01). Furthermore, there was a significant correlation between the IC(50)s of FK506 and plasma anti-TSST-1 IgE levels (p < 0.01).
  
  
  CONCLUSIONS
  We showed that PBMCs in severe AD patients exhibited lower sensitivity to FK506, and had higher plasma levels of anti-TSST-1 IgE as compared to the mild AD patients. SAgs appear to be one of the causes of decreased PBMC sensitivity to FK506, and therefore an alternative treatment would be useful based on the individual drug sensitivity data and anti-TSST-1 IgE levels.
authors.affiliation: Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Science, Tokyo, Japan. kahimi28@ps.toyaku.ac.jp
authors.forename: Hisayo
authors.initials: H
authors.lastname: Fukushima
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
authors.forename: Naoko
authors.initials: N
authors.lastname: Shibayama
authors.forename: Keishi
authors.initials: K
authors.lastname: Miwa
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Ito
authors.forename: Masukichi
authors.initials: M
authors.lastname: Saito
authors.forename: Haruko
authors.initials: H
authors.lastname: Sumida
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oyake
authors.forename: Ryoji
authors.initials: R
authors.lastname: Tsuboi
authors.forename: Kitaro
authors.initials: K
authors.lastname: Oka
mesh_terms: D000328:Adult; D001427:Bacterial Toxins / Q000494:pharmacology; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000503:physiopathology; D004351:Drug Resistance / Q000276:immunology*; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000097:blood / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D012720:Severity of Illness Index; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D007166:Immunosuppressive Agents; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D007073:Immunoglobulin E; D016559:Tacrolimus