Genetic Analysis for Diagnosis, Monitoring and Predicting Response to Therapy in Kawasaki Disease, Vasculitis and Other Vasculopathies
Kawasaki disease (KD) is an inflammatory condition that is the leading cause of acquired heart disease in children in the United States. KD patients can experience debilitating coronary artery aneurysms followed by thrombosis, stenosis, and even myocardial infarction and death. KD is currently diagnosed on the basis of clinical criteria alone and is often missed or diagnosed too late for therapy to prevent the onset of coronary artery disease. However, if KD is diagnosed and treated early, most commonly with intravenous immunoglobulin therapy (IVIG), the associated health complications and mortality rate are minimal.
Dr. Portman’s lab has developed a new approach for diagnosing and monitoring patients with KD and other vasculopathies. The approach involves isolation of extracellular vesicles called exosomes from patient serum samples, with subsequent sequence analysis of the RNA content of exosomes expressing certain cell-specific antigen markers. Expression patterns identified by this method could also be used to diagnose other types of vascular injury and track their progression.
Dr. Portman’s lab has also made a key discovery about gene promoter variants and IVIG treatment response in KD. IVIG is widely believed to work by binding to Fc-gamma receptors (FCGRs) on certain types of blood or inflammatory cells. Dr. Portman’s team found that some patients have variations in the genes that regulate FCGRs, and that these variations lead to abnormal or mutated FCGRs that can’t properly bind with the IVIG. By analyzing KD patients’ genes, work is progressing on understanding how genetic variations can predict a patient’s response to IVIG.
Stage of Development
- Pre-clinical in vitro
- Pre-clinical in vivo
- Clinical trial
- Sample access
- Collaborative research opportunity
- Sponsored research agreement
- Kourtidou S, Slee AE, Bruce ME, Wren H, Mangione-Smith RM, Portman MA. Kawasaki disease substantially impacts health-related quality of life. J Pediatr. 193: 155-63 e5.
- Portman MA, Shrestha S. One size does not fit all: Genetic prediction of Kawasaki disease treatment response in diverse populations. Circ Cardiovasc Genet. 2017;10. PMID: 29025763 DOI:10.1161/CIRCGENETICS.117.001917
- Yeter D, Portman MA, Aschner M, et al. Ethnic Kawasaki disease risk associated with blood mercury and cadmium in U.S. children. Int J Environ Res Public Health. 2016; 13; 101.
- Shendre A, Wiener HW, Zhi D, Vazquez Al, Portman MA, Shrestha S. High-density genotyping of immune loci in Kawasaki disease and IVIG treatment response in European-American case-parent trio study. Genes lmmn. 2014; 15: 534542. Doi: 10.1038/gene.2014.47.
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