title: Immune-monitoring in Kawasaki disease patients treated with infliximab and intravenous immunoglobulin.
abstract: The expansion of regulatory T cells (Treg ) controls inflammation in children with acute Kawasaki disease (KD). Blockade of tumour necrosis factor (TNF)-α is an emerging therapy for KD patients with refractory inflammation, but there is concern that this therapy could impede the host immune regulation. To define the effect of TNF-α blockade, we conducted ex-vivo immune-monitoring in KD subjects who participated in a randomized, double-blind, placebo-controlled clinical trial of the addition of infliximab to standard intravenous immunoglobulin (IVIG) therapy. We enumerated circulating myeloid and plasmocytoid dendritic cells (DC), regulatory T cells (Treg ) and memory T cells (Tmem ) in 14 consecutive, unselected KD patients (seven treated with IVIG, seven with IVIG + infliximab) at three time-points: (i) acute phase prior to treatment, (ii) subacute phase and (iii) convalescent phase. Myeloid DC (mDC), but not plasmacytoid DC (pDC), were numerous in the peripheral blood in acute KD subjects and decreased in the subacute phase in both IVIG(-) and IVIG (+)  infliximab-treated groups. The co-stimulatory molecule for antigen presentation to T cells and CD86 decreased in mDC from acute to subacute time-points in both treatment groups, but not in the single patient who developed coronary artery aneurysms. We also defined tolerogenic mDC that expand in the subacute phase of KD not impaired by infliximab treatment. Treg and Tmem expanded after treatment with no significant differences between the two groups. Treatment of KD patients with infliximab does not adversely affect generation of tolerogenic mDC or the development of T cell regulation and memory.
authors.affiliation: Department of Pediatrics, School of Medicine, University of California San Diego and Rady Children's Hospital, La Jolla, CA, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Burns
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.forename: M
authors.initials: M
authors.lastname: Bujold
authors.forename: C
authors.initials: C
authors.lastname: Shimizu
authors.forename: J T
authors.initials: JT
authors.lastname: Kanegaye
authors.forename: A H
authors.initials: AH
authors.lastname: Tremoulet
authors.forename: A
authors.initials: A
authors.lastname: Franco
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D051940:B7-2 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003323:Coronary Aneurysm / Q000139:chemically induced; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use; D007156:Immunologic Memory; D007223:Infant; D007249:Inflammation / Q000276:immunology; D000069285:Infliximab; D018655:Lymphocyte Count; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000188:drug therapy*; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology; D010919:Placebos; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D051940:B7-2 Antigen; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
keywords: Kawasaki disease; T cells; dendritic cells; infliximab; vascular inflammation
references.citation: Autoimmunity. 2010 Jun;43(4):317-24
references.pmid: 20166878
references.citation: Ann Rheum Dis. 2008 Jun;67(6):762-8
references.pmid: 17965117
references.citation: Hum Immunol. 2009 Dec;70(12):966-9
references.pmid: 19664675
references.citation: Scand J Immunol. 2013 Mar;77(3):213-20
references.pmid: 23298344
references.citation: Pediatrics. 1974 Sep;54(3):271-6
references.pmid: 4153258
references.citation: J Pediatr. 2008 Dec;153(6):833-8
references.pmid: 18672254
references.citation: J Exp Med. 1994 Apr 1;179(4):1109-18
references.pmid: 8145033
references.citation: Nat Med. 2013 Mar;19(3):322-8
references.pmid: 23396208
references.citation: Annu Rev Immunol. 2004;22:745-63
references.pmid: 15032595
references.citation: Nat Genet. 2008 Jan;40(1):35-42
references.pmid: 18084290
references.citation: Blood. 2010 Aug 12;116(6):935-44
references.pmid: 20448110
references.citation: Hum Immunol. 2013 Apr;74(4):406-11
references.pmid: 23238214