CD84 is markedly up-regulated in Kawasaki disease arteriopathy

Authors

  • R. Reindel,

    1. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, USA
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  • J. Bischof,

    1. Cancer Biology and Epigenomics Program, Ann and Robert H. Lurie Children's Hospital of Chicago Research Center, Chicago, USA
    Current affiliation:
    1. Computation Institute, University of Chicago, Chicago, IL, USA
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  • K.-Y. A. Kim,

    1. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, USA
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  • J. M. Orenstein,

    1. Department of Pathology, George Washington University School of Medicine, Washington, DC, USA
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  • M. B. Soares,

    1. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, USA
    2. Cancer Biology and Epigenomics Program, Ann and Robert H. Lurie Children's Hospital of Chicago Research Center, Chicago, USA
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  • S. C. Baker,

    1. Department of Microbiology/Immunology, Loyola University Stritch School of Medicine, Maywood, IL, USA
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  • S. T. Shulman,

    1. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, USA
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  • E. J. Perlman,

    1. Department of Pathology, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, USA
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  • M. W. Lingen,

    1. Department of Pathology, University of Chicago Pritzker School of Medicine, Chicago, USA
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  • A. J. Pink,

    1. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, USA
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  • C. Trevenen,

    1. Department of Pathology and Laboratory Medicine, Alberta Children's Hospital, Calgary, Alberta, Canada
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  • A. H. Rowley

    Corresponding author
    1. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, USA
    • Correspondence: A. H. Rowley, Northwestern University Feinberg School of Medicine, 310 E Superior Street, Morton 4-625B, Chicago, IL 60611, USA.

      E-mail: a-rowley@northwestern.edu

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Summary

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.

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