title: Defective FOXP3 expression in patients with acute Kawasaki disease and restoration by intravenous immunoglobulin therapy.
abstract: OBJECTIVE
  The aims of this study were: 1) to investigate forkhead box P3 (FOXP3) expression in patients with Kawasaki disease (KD), exploring possible differences during the acute phase and after defervescence; 2) to evaluate a possible association of the FOXP3 single nucleotide polymorphism (SNP) 543 (SNP ID: rs2232367) with KD.
  
  
  METHODS
  FOXP3 expression was evaluated on 8 children with KD and 15 healthy children by flow cytometry and Real-Time polymerase chain reaction (RT-PCR). FOXP3 SNP 543 was genotyped by denaturing high-performance liquid chromatography (DHPLC) and sequencing on DNA samples from 58 additional children with KD and 114 healthy donors.
  
  
  RESULTS
  The frequencies of CD4+CD25 +FOXP3+ regulatory T cells were significantly (p=0.0002) lower during the acute phase of KD than in sex- and age-matched healthy donors (median % + SD: 4.8+/-1.3 vs. 7.7+/-1.7) and a similar tendency was revealed for FOXP3 mRNA transcripts (p<0.0001). FOXP3 expression increased significantly, at both protein and mRNA levels, after intravenous immunoglobulin (IVIG) therapy treatment and achieving complete remission of disease (at least 48 hrs; median 9.5 days, range 2-30). Of the 58 patients screened, only one female subject (1.7%) carried the presence of 543 SNP in heterozygosis (C>T; for a total of 1 allele out of 88), with no difference between KD patients and controls (0.0%, 0/203 alleles).
  
  
  CONCLUSIONS
  Our data reinforce the notion of an impaired immunoregulation in KD, suggesting also a role of IVIG treatment in modifying the Treg compartment. FOXP3 SNP 543 does not seem to be involved in susceptibility to KD in Italian children.
authors.affiliation: Department of Paediatrics, University of Florence and Anna Meyer Children's Hospital, Florence, Italy. b.olivito@meyer.it
authors.forename: Biagio
authors.initials: B
authors.lastname: Olivito
authors.forename: Andrea
authors.initials: A
authors.lastname: Taddio
authors.forename: Gabriele
authors.initials: G
authors.lastname: Simonini
authors.forename: Cristina
authors.initials: C
authors.lastname: Massai
authors.forename: Sara
authors.initials: S
authors.lastname: Ciullini
authors.forename: Eleonora
authors.initials: E
authors.lastname: Gambineri
authors.forename: Maurizio
authors.initials: M
authors.lastname: de Martino
authors.forename: Chiara
authors.initials: C
authors.lastname: Azzari
authors.forename: Rolando
authors.initials: R
authors.lastname: Cimaz
mesh_terms: D000208:Acute Disease; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007223:Infant; D007558:Italy; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016756:Immunoglobulins, Intravenous; D012333:RNA, Messenger