title: Transcriptional regulation by infliximab therapy in Kawasaki disease patients with immunoglobulin resistance.
abstract: BACKGROUND
  Infliximab (IFX), a known monoclonal antibody against tumor necrosis factor-α (TNF-α), is used to treat Kawasaki disease (KD) patients with intravenous immunoglobulin (IVIG) resistance. The transcriptional modulation of inflammation following IFX therapy has not been reported in KD patients.
  
  
  METHODS
  We investigated the transcript abundance profiles in whole blood obtained from eight IVIG-resistant KD subjects treated with IFX therapy using microarray platforms and compared them with those in initially IVIG-responsive subjects. A pathway analysis was performed using WikiPathways to search for the biological pathways of the transcript profiles. Four transcripts changed by IFX therapy were subsequently validated using quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  The pathway analysis showed the reduced abundance of transcripts in the nucleotide-binding oligomerization domain, matrix metalloproteinase (MMP), and inflammatory cytokine pathways and the increased abundance of transcripts in the T-cell receptor, apoptosis, TGF-β, and interleukin-2 pathways. Additionally, the levels of four transcripts (peptidase inhibitor-3, MMP-8, chemokine receptor-2, and pentraxin-3) related to KD vasculitis and IVIG resistance decreased after IFX therapy.
  
  
  CONCLUSIONS
  The administration of IFX was associated with both the signaling pathways of KD inflammation and several transcripts related to IVIG resistance factors. These findings provide strong theoretical support for the use of IFX in KD patients with IVIG resistance.
authors: Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan.
authors: Yoshihito
authors: Y
authors: Ogihara
authors: Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan.
authors: Shohei
authors: S
authors: Ogata
authors: Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan.
authors: Keiko
authors: K
authors: Nomoto
authors: Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan.
authors: Takasuke
authors: T
authors: Ebato
authors: Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan.
authors: Kayoko
authors: K
authors: Sato
authors: Department of Medical Engineering and Technology, Kitasato University School of Allied Health Sciences, Sagamihara, Japan.
authors: Kenichi
authors: K
authors: Kokubo
authors: Department of Medical Engineering and Technology, Kitasato University School of Allied Health Sciences, Sagamihara, Japan.
authors: Hirosuke
authors: H
authors: Kobayashi
authors: Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Japan.
authors: Masahiro
authors: M
authors: Ishii
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D030541:Databases, Genetic; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007223:Infant; D000069285:Infliximab; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D000069285:Infliximab