# Genetic Prediction for Treatment Resistance in Kawasaki Disease

> **NIH NIH R01** · SEATTLE CHILDREN'S HOSPITAL · 2021 · $56,324

## Abstract

PROJECT SUMMARY
Kawasaki Disease (KD) is systemic autoinflammatory vasculitis occurring in children and showing predilection
for attacking the coronary arteries. Despite 60 years of research, the etiology and pathogenesis for KD still
require elucidation. The predominant hypothesis regarding pathogenesis involves an unknown antigen,
possibly microbial, or super-antigen induced hyperimmune response occurring in genetically susceptible
individuals. Treatment includes inflammatory suppression with high dose immunoglobulin. However,
response, defined as persistent of fever, or continuing coronary vasculitis characterized by dilation and
aneurysm formation, is highly variable. The parent grant tests the hypothesis that treatment response depends
on pharmacogenetics, which is currently being probed with whole genome sequencing. Disease severity,
particularly formation of giant coronary aneurysms, could also depend on the pathogen signaling the immune
response. Currently, the world faces a pandemic from the novel human corona virus SARS-COV-2 resulting in
development of Covid-19 disease. This virus promotes a dramatic systemic inflammatory response, in some
ways mirroring that occurring in KD. Thus, prior studies have explored and suggested a role for corona virus
HCoV-NL63 in KD pathogenesis, although subject numbers displaying both KD and serological evidence for
corona have been limited due to relatively low infectivity of corona virus overall. In contrast, SARS-COV-2
shows high human to human transmission, and modeling shows that millions of Americans will eventually be
infected. This transmission alters the landscape for evaluating a potential role for corona viruses in
pathogenesis of KD in children. Covid-19 is particularly intriguing for KD as the SARS-COV-2 spike protein
binds to angiotensin converting enzyme2 (ACE2) as a receptor and promotes cellular entry of the virus. ACE2
enzymatically directs angiotensin2 to angiotensin (1-9), which promotes coronary arterial dilation, an important
aspect of KD. SARS-COV-2 infection severity in children currently appears to be mild leading to low rates of
testing (although we are now receiving reports of respiratory distress and even death in children and infants in
the U.S and throughout the world). Thus, the relationship of SARS-COV-2 and autoinflammatory pediatric
diseases such as KD remains unknown. This study will use existing grant infrastructure to determine
relationships between SARS-COV-2 infection and KD. We will also use this opportunity to determine antibody
response to SARS-COV-2 exposure in a febrile and afebrile Pediatric populations. The supplement scope will
be supported by UAB investigators, who are at the forefront of developing serological testing for SARS-COV-2,
as well as Seattle Children’s located at the initial U.S epicenter for the pandemic.

## Key facts

- **NIH application ID:** 10150348
- **Project number:** 3R01HL146130-03S1
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Michael A Portman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $56,324
- **Award type:** 3
- **Project period:** 2018-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150348

## Citation

> US National Institutes of Health, RePORTER application 10150348, Genetic Prediction for Treatment Resistance in Kawasaki Disease (3R01HL146130-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10150348. Licensed CC0.

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