Genetics and Kawasaki Disease: Inflammatory disease in children due to pathogens

Kawasaki disease is in the news these days in reference to kids with COVID-19 infections. It is an inflammatory condition that can occur in kids when they have been sick with a viral or bacterial illness.

This article explains what Kawasaki disease is and the (rare!) cases with COVID-19. It dives into the genetic variants that increase susceptibility to Kawasaki disease.

What is Kawasaki Disease?

Kawasaki disease is a condition that causes inflammation in the endothelial cells that make up the medium-sized blood vessel and the muscle of the heart.  It generally strikes infants and young children, ages 5 and under.

Symptoms of Kawasaki disease can include: [ref][ref]

  • rash, especially mouth and eyes
  • fever, lasting for 5+ days
  • red eyes
  • red palms and swollen feet
  • swollen, red tongue
  • enlarge lymph nodes in the neck
  • irritability

For most kids, the acute disease phase lasts less than 2 weeks, and it usually clears up on its own.  The problem comes for the 25% of patients that end up with a longer-lasting disease, which can develop into long-lasting problems with their heart and blood vessels. [ref]

Cause of Kawasaki Disease:

Researchers have debated the causes of Kawasaki disease for decades. Some researchers once theorized that it was triggered by an antigen (produced after an infection) that causes an autoimmune type reaction against the cells in the blood vessel walls. The problem with calling it an autoimmune type of reaction is that Kawasaki disease only lasts for a short period of time, unlike long-lasting autoimmune diseases. Most researchers believe it is caused by the activation of the immune system by a virus in the coronary arteries. [ref] [ref]

Kawasaki disease is fairly common in Asian countries such as Korea, Japan, and China. It is diagnosed much less frequently in Western countries. [ref]

Inflammatory cytokines are elevated in children with Kawasaki disease. It is thought that a pathogen (virus, bacteria, fungi) causes an inflammatory and immune response that leads to the destruction of the epithelial cells in medium-size blood vessels.[ref]

In a study from 2014, researcher found that cases of Kawasaki disease were caused by several different viruses including “enterovirus (16.8% vs. 4.4%, p < 0.001), adenovirus (8.0% vs. 1.8%, p = 0.007), human rhinovirus (26.5% vs. 9.7%, p < 0.001), and coronavirus (7.1% vs. 0.9%, p = 0.003″. [ref]

There are also a number of bacterial pathogens, including staphylococcus aureus and streptococcus pyrogenes, that are suspected of causing Kawasaki disease. The figure below (Creative Commons license) outlines the mechanisms of how Kawasaki disease happens.[ref]

Kawasaki Disease and COVID-19:

There have been many news reports (April and May 2020) of kids getting Kawasaki disease like symptoms after getting the SARS-CoV2 virus. And from the number of news stories on the topic, parents may be worried.

A recent preprint of a study explained that only about 100 cases of Kawasaki disease in children (ages 6mo to 9 years) have been reported during this pandemic. Most of the cases in the study were in Europe. Cases seem to occur about 2 to 4 weeks after infection.  The researchers note that Kawasaki disease is a rare complication of COVID-19 and estimate that it occurs in 0.01 – 0.3% of infected kids. [ref]

When you consider the very low number of cases of COVID-19 in children, it is not something that most parents need to be concerned about. Instead, realize that Kawasaki disease is something that occurs more commonly with other childhood illnesses.


Genetic variants associated with Kawasaki Disease

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I want to make clear that carrying the genetic variants below definitely does not mean that an individual will get Kawasaki disease — it just means that there is a statistical increase in risk.

More importantly, understanding which genes are involved can help researchers and doctors better understand how to treat the disease. Knowing where the genetic susceptibility lies can help to know the root cause.

FCGR2A gene: codes for a receptor that is involved in the immune response to antigens

Check your genetic data for rs1801274 (23andMe v4, v5; AncestryDNA):

  • G/G: decreased susceptibility to Kawasaki disease [ref] [ref][ref]
  • A/G: decreased susceptibility to Kawasaki disease
  • A/A: typical risk

Members: Your genotype for rs1801274 is .

ITPKC gene: codes for inositol-triphosphate 3-kinase which regulates T-cell activation

Check your genetic data for rs28493229 (23andMe v4, v5; AncestryDNA):

  • G/G: increased susceptibility to Kawasaki disease [ref]
  • C/G: increased susceptibility to Kawasaki disease
  • C/C: typical risk

Members: Your genotype for rs28493229 is .

RAB4B gene: codes for Ras-related protein Rab-4B

Check your genetic data for rs2233152 (23andMe v4, v5; AncestryDNA):

  • G/G: increased susceptibility to Kawasaki disease [ref]
  • A/G: increased susceptibility to Kawasaki disease
  • A/A: typical risk

Members: Your genotype for rs2233152 is .

BLK gene: codes for a B-lymphocyte kinase

Check your genetic data for rs2736340 (23andMe v4. v5; AncestryDNA):

  • T/T: increased susceptibility to Kawasaki disease[ref]
  • C/T: increased susceptibility to Kawasaki disease (common variant)
  • C/C: typical risk

Members: Your genotype for rs2736340 is .

CD40 gene: codes for a protein that is needed in antigen-presenting cells in the immune system

Check your genetic data for rs1569723 (23andMe v4. v5; AncestryDNA):

  • A/A: most common genotype, increased susceptibility to Kawasaki disease[ref]
  • A/C: increased susceptibility to Kawasaki disease (common variant)
  • C/C: less susceptibility to Kawasaki disease.

Members: Your genotype for rs1569723 is .

INFG gene: codes for interferon-gamma, an important part of the initial immune response to pathogens

Check your genetic data for rs1861493 (23andMe v4; AncestryDNA):

  • G/G: better response to IV immunoglobulin therapy in Kawasaki disease patients [ref]
  • A/G: better response to IV immunoglobulin therapy in Kawasaki disease patients
  • A/A: lower plasma IFN-γ level, increased risk of coronary artery aneurysms in Kawasaki disease patients

Members: Your genotype for rs1861493 is .


Lifehacks:

This is not one of those DIY situations… If you suspect that your child has Kawasaki disease, you should take him/her to the doctor. The risk of long-term heart problems is real, and there are treatments such as IV immunoglobulin therapy that can work.

 


Related Articles:

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Acute Respiratory Distress Syndrome (ARDS) genes
ARDS is caused by an overwhelming immune response to a virus, bacteria, or lung injury. Learn more about which of your immune system genes are involved in ARDS.

Viruses: Are you susceptible to coronavirus, flu, and more?
Your genetic variants shape your immune system and give you superpowers against some pathogens – and perhaps more susceptible to others.



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.