title: Lack of CD4⁺CD25⁺FOXP3⁺ regulatory T cells is associated with resistance to intravenous immunoglobulin therapy in patients with Kawasaki disease.
abstract: The aim of this study was to investigate changes in CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) throughout the clinical course of Kawasaki disease (KD) and correlations with response to intravenous immunoglobulin (IVIg) therapy. Participants comprised 18 patients who fulfilled the diagnostic criteria for KD and 20 healthy subjects. Expressions of CD25 and FOXP3 among all CD4(+) T cells in peripheral blood mononuclear cells were analyzed by flow cytometry before and 7 and 30 days after IVIg therapy. Before treatment, percentages of CD4(+)CD25(+)FOXP3(+) Tregs among total CD4(+) Tregs were significantly lower among KD patients (4.19 %; range, 0.16-8.11 %) than among healthy subjects (7.32 %; 4.18-13.42 %; P = 0.0001). Both percentages and absolute numbers of CD4(+)CD25(+)FOXP3(+) Tregs on day  7 after IVIg therapy were significantly increased compared with values before treatment (8.02 % (range, 0.51-12.6 %) vs. 4.19 % (range, 0.16-8.11 %), P = 0.0005; 93.25/ μL (range, 6.67-258.05) vs. 41.85/ μL (range, 0.44-160.62), P < 0.0001, respectively). Moreover, percentages and absolute numbers of CD4(+)CD25(+)FOXP3(+) Tregs before treatment were significantly lower in the IVIg-resistant group than in the IVIg-sensitive group (0.18 % (range, 0.16-3.34 %) vs. 4.52 % (range, 2.8-8.11 %), P = 0.0022; 0.68/μL (range, 0.44-53.81) vs. 51.66/μL (range, 2.88-160.62), P = 0.0098, respectively). The frequency of CD4(+)CD25(+)FOXP3(+) Tregs in four of the five IVIg-resistant patients at diagnosis was more than 3 standard deviations below that in healthy subjects. Two of these four patients displayed coronary abnormalities, and one of these two patients developed coronary aneurysm.
  
  
  CONCLUSIONS
  Lack of CD4(+)CD25(+)FOXP3(+) Tregs before treatment may predict resistance to IVIg therapy in patients with KD.
authors: Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors: Yu
authors: Y
authors: Hirabayashi
authors: Yoshiyuki
authors: Y
authors: Takahashi
authors: Yinyan
authors: Y
authors: Xu
authors: Kazuyuki
authors: K
authors: Akane
authors: Itzel Bustos
authors: IB
authors: Villalobos
authors: Yusuke
authors: Y
authors: Okuno
authors: Shinji
authors: S
authors: Hasegawa
authors: Hideki
authors: H
authors: Muramatsu
authors: Asahito
authors: A
authors: Hama
authors: Taichi
authors: T
authors: Kato
authors: Seiji
authors: S
authors: Kojima
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003324:Coronary Artery Disease / Q000150:complications / Q000276:immunology; D004351:Drug Resistance / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000276:immunology / Q000627:therapeutic use*; D007223:Infant; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D053645:Interleukin-2 Receptor alpha Subunit