Defective FOXP3 expression in patients with acute Kawasaki disease and restoration by intravenous immunoglobulin therapy.

Abstract

OBJECTIVES:

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: Biagio Olivito, Andrea Taddio, Gabriele Simonini, Cristina Massai, Sara Ciullini, Eleonora Gambineri, Maurizio de Martino, Chiara Azzari, Rolando Cimaz
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) 2010 Jan-Feb Vol. 28 Issue 1 Suppl 57 Pg. 93-7 ISSN: 0392-856X [Print] Italy
• PMID: 20412712 (Publication Type: Journal Article)

Chemical References

• FOXP3 protein, human
• Forkhead Transcription Factors
• Immunoglobulins, Intravenous
• RNA, Messenger

Topics

• Acute Disease
• Child
• Child, Preschool
• Female
• Flow Cytometry
• Forkhead Transcription Factors (genetics, metabolism)
• Genotype
• Humans
• Immunoglobulins, Intravenous (administration & dosage)
• Infant
• Italy
• Male
• Mucocutaneous Lymph Node Syndrome (genetics, immunology, therapy)
• Polymorphism, Single Nucleotide
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocytes, Regulatory (immunology)