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Past Research Studies

New treatment for children who fail to respond to IVIG infusion

Approximately 20% of children with KD fail to respond to the first dose of gamma globulin (IVIG). Infliximab (Remicade®) is an antibody that binds TNF-α, a pro-inflammatory molecule that is elevated in the blood of children with KD. This therapeutic antibody may help turn off the inflammation in children who do not completely respond to IVIG.

  • Burns JC, Best BM, Mejias A, Mahony L, Fixler DE, Jafri HS, Melish ME, Jackson MA, Asmar B, Lang D, Connor JD, Capparelli EV, Keen ML, Mamun K, Keenan G, Ramilo O. Infliximab treatment of IVIG-resistant Kawasaki disease. J Pediatr. 2008; 153(6):833-8.
  • Tremoulet AH, Best BM, Song S, Wang S, Corinaldesi E, Eichenfield J, Burns JC. Resistance to intravenous immunoglobulin in children with Kawasaki Disease. J Pediatr. 2008;153:117-121.
  • Burns JC, Mason WH, Hauger SB, Janai H, Bastian JF, Wohrley JD, Balfour I, Shen CA, Michel ED, Shulman ST, Melish ME. Infliximab treatment for refractory Kawasaki syndrome. J Pediatr. 2005;146:662-667.

Epidemiology of KD in San Diego County, Dr. Annie Kao

Reporting of KD cases to the county health department is a requirement in California. This study was performed in collaboration with the San Diego Dept. of Health Services and describes all patients diagnosed with KD in San Diego County during the 5-yr. study period from 1998-2003. For the first time, clustering of KD cases in time and space was documented, which further suggests an infectious disease trigger for KD.

  • Wilder MS, Palinkas LA, Kao AS, Bastian JF, Burns JC. Delayed diagnosis by physicians contributes to the development of coronary artery aneurysms in patients with Kawasaki syndrome. Ped Inf Dis J. 2007; 26: 256-260.

Genetics and KD

Regions of the DNA that may influence susceptibility to KD and outcome were examined in a mixed ethnic/racial cohort of KD patients and their families from North America. We represent the U.S. in the International KD Genetics Consortium and are collaborating with research groups from the UK, Canada, Holland, Australia, and Singapore in an effort to further our knowledge about how genes affect both susceptibility to KD and disease outcome. Families with multiple affected members are now being recognized in North America and a family linkage study to examine the DNA from families with multiple affected members has just been completed. We welcome participation of all KD families in our genetic studies. Contact us at kdgenetics@ucsd.edu for more information.

  • Khor CC, Davila S, Shimizu C, Sheng S, Matsubara T, Suzuki Y, Newburger JW, Baker A, Burgner D, Breunis W, Kuijpers T, Wright VJ, Levin M, Hibberd ML, Burns JC. Genome wide linkage and association mapping identify susceptibility alleles in ABCC4 for Kawasaki disease. In revision, Journal of Medical Genetics. J Med Genet. 2011 May 13 [Epub ahead of print].
  • Shimizu C, Jain S, Lin KO, Molkara D, Frazer JR, Sun S, Baker AL, Newburger JW, Rowley AH, Shulman ST, Davila S, Hibberd ML, Burgner D, Breunis WB, Kuijpers TW, Wright VJ, Levin M, Popper SJ, Relman DA, Fury W, Lin C, Mellis S, Tremoulet AH, Burns JC. Transforming growth factor-β signaling pathway in patients with Kawasaki disease. Circulation: Cardiovascular Genetics 2011;4:16-25.
  • Shimizu C, Matsubara T, Onouchi Y, Jain S, Sun S, Nievergelt CM, Shike H, Takegawa T, Furukawa, Akagi T, Newburger JW, Baker AL, Burgner D, Hibberd ML, Davila S, Levin M, Mamtani M, He W, Ahuja SK, Burns JC. Matrix metalloproteinases haplotypes are associated with coronary artery aneurysm formation in patients with Kawasaki disease. J Human Genetics 2010;55(12):779-84.
  • Burgner D, Davila S, Breunis WB, Ng SB, Li Y, Bonnard C, Ling L, Wright VJ, Odam M, Shimizu C, Burns JC, Levin M, Kuijpers TW, Hibberd ML for the International Kawasaki Disease Genetics Consortium. A genome-wide association study identifies novel and functionally related susceptibility loci for Kawasaki disease. PloS Genetics. 2009 Jan:5(1):e1000319.
  • Onouchi Y, Gunji T, Burns JC, Shimizu C, Newburger JW, Yashiro M, Nakamura Y, Yanagawa H, Wakui K, Fukushima Y, Kishi F, Hamamoto K, Terai M, Sato Y, Ouchi K, Saji T, Narai A, Kaburagi Y, Yoshikawa T, Suzuki K, Tanaka T, Nagai T, Cho H, Fujino A, Sekine A, Nakmuchi R, Tatsuhiko T, Kawasaki T, Nakamura Y, Hata A. IPTKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nature Genetics 2008 Jan;40(1):35-42.
  • Dergun M, Kao A, Hauger SB, Newburger JW, Burns JC. Familial occurrence of Kawasaki syndrome in North America. Arch Pediatr Adolesc Med. 2005;159:876-881.
  • Burns JC, Shimizu C, Gonzalez E, Kulkarni H, Patel S, Shike J, Sundel RS, Newburger JW, Ahuja SK. Genetic variations in the receptor-ligand pair, CCR5 and CCL3L1, are important determinants of susceptibility to Kawasaki disease. J Infect Dis. 2005;192:344-349.
  • Burns JC, Shimizu C, Shike H, Newburger JW, Sundel RS, Matsubara T, Ishikawa Y, Cheng S, Grow MA, Steiner L, Brophy VA, Cantor R. Family-based association analysis of genes in inflammatory and cardiovascular pathways implicates IL-4 in Kawasaki Disease. Genes and Immunity 2005;6:438-444.

Climate Study

In collaboration with Dan Cayan, Director, Climate Center, Scripps Institution of Oceanography, UCSD, we studied possible links between KD and seasons of the year. In Japan, there are two peaks, one in the winter months (Jan.-March) and a second in mid-summer (July/August). This pattern for KD also is evident in San Diego County. A new analysis of time series of KD patients from all over the world is being lead by Dr. Xavier Rodo in collaboration with our group and the SIO team. This represents a broad collaboration of KD researchers from both the northern and southern hemispheres and should yield the most comprehensive understanding of how the “KD agent” moves around the globe. Stay tuned!

  • Burns JC, Cayan DR, Tong F, Turner CL, Shike H, Kawasaki T, Nakamura Y, Yashiro M, Yanagawa H. Seasonality and temporal clustering of Kawasaki Syndrome in Japan, 1987-2000. Epidemiology 2005;16:220-225.