Gene expression profiling of the effect of high-dose intravenous Ig in patients with Kawasaki disease.
Kawasaki disease (KD) is an acute vasculitis of infants and young children, preferentially affecting the coronary arteries. Intravenous infusion of high dose Ig (IVIG) effectively reduces systemic inflammation and prevents coronary artery lesions in KD. To investigate the mechanisms underlying the therapeutic effects of IVIG, we examined gene expression profiles of PBMC and purified monocytes obtained from acute patients before and after IVIG therapy. The results suggest that IVIG suppresses activated monocytes and macrophages by altering various functional aspects of the genes of KD patients. Among the 18 commonly decreased transcripts in both PBMC and purified monocytes, we selected six genes, FCGR1A, FCGR3A, CCR2, ADM, S100A9, and S100A12, and confirmed the microarray results by real-time RT-PCR. Moreover, the expressions of FcgammaRI and FcgammaRIII on monocytes were reduced after IVIG. Plasma S100A8/A9 heterocomplex, but not S100A9, levels were elevated in patients with acute KD compared with those in febrile controls. Furthermore, S100A8/A9 was rapidly down-regulated in response to IVIG therapy. Persistent elevation of S100A8/A9 after IVIG was found in patients who later developed coronary aneurysms. These results indicate that the effects of IVIG in KD may be mediated by suppression of an array of immune activation genes in monocytes, including those activating FcgammaRs and the S100A8/A9 heterocomplex.
Abe
Jun
J
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. jabe@nch.go.jp
Jibiki
Toshiaki
T
Noma
Seiji
S
Nakajima
Tosiharu
T
Saito
Hirohisa
H
Terai
Masaru
M
D000208:Acute Disease; D040501:Calgranulin A / Q000096:biosynthesis; D040502:Calgranulin B / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D004334:Drug Administration Schedule; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009080:Mucocutaneous Lymph Node Syndrome / Q000235:genetics* / Q000628:therapy*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology
D040501:Calgranulin A; D040502:Calgranulin B; C489017:FCGR1A protein, human; C496124:FCGR3A protein, human; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG