title: CD84 is markedly up-regulated in Kawasaki disease arteriopathy.
abstract: The major goals of Kawasaki disease (KD) therapy are to reduce inflammation and prevent thrombosis in the coronary arteries (CA), but some children do not respond to currently available non-specific therapies. New treatments have been difficult to develop because the molecular pathogenesis is unknown. In order to identify dysregulated gene expression in KD CA, we performed high-throughput RNA sequencing on KD and control CA, validated potentially dysregulated genes by real-time reverse transcription-polymerase chain reaction (RT-PCR) and localized protein expression by immunohistochemistry. Signalling lymphocyte activation molecule CD84 was up-regulated 16-fold (P < 0·01) in acute KD CA (within 2 months of onset) and 32-fold (P < 0·01) in chronic CA (5 months to years after onset). CD84 was localized to inflammatory cells in KD tissues. Genes associated with cellular proliferation, motility and survival were also up-regulated in KD CA, and immune activation molecules MX2 and SP140 were up-regulated in chronic KD. CD84, which facilitates immune responses and stabilizes platelet aggregates, is markedly up-regulated in KD CA in patients with acute and chronic arterial disease. We provide the first molecular evidence of dysregulated inflammatory responses persisting for months to years in CA significantly damaged by KD.
authors.affiliation: Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, USA.
authors.forename: R
authors.initials: R
authors.lastname: Reindel
authors.forename: J
authors.initials: J
authors.lastname: Bischof
authors.forename: K-Y A
authors.initials: KY
authors.lastname: Kim
authors.forename: J M
authors.initials: JM
authors.lastname: Orenstein
authors.forename: M B
authors.initials: MB
authors.lastname: Soares
authors.forename: S C
authors.initials: SC
authors.lastname: Baker
authors.forename: S T
authors.initials: ST
authors.lastname: Shulman
authors.forename: E J
authors.initials: EJ
authors.lastname: Perlman
authors.forename: M W
authors.initials: MW
authors.lastname: Lingen
authors.forename: A J
authors.initials: AJ
authors.lastname: Pink
authors.forename: C
authors.initials: C
authors.lastname: Trevenen
authors.forename: A H
authors.initials: AH
authors.lastname: Rowley
mesh_terms: D000208:Acute Disease; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D001792:Blood Platelets / Q000276:immunology*; D048708:Cell Growth Processes / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002908:Chronic Disease; D003331:Coronary Vessels / Q000473:pathology; D005260:Female; D057166:High-Throughput Screening Assays; D006801:Humans; D007223:Infant; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000097:blood / Q000235:genetics / Q000276:immunology*; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism*; D010974:Platelet Aggregation / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D000071176:Signaling Lymphocytic Activation Molecule Family; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D061205:Vascular Calcification / Q000097:blood / Q000235:genetics / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D034961:Antigens, Nuclear; C498970:CD84 protein, human; C579068:MX2 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; C102470:SP140 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family; D014157:Transcription Factors
keywords: CD84; Kawasaki disease; coronary artery aneurysm; inflammation; vasculitis