HomeLifestyleHealth & FitnessHigher Body Temperature May Trigger Inflammatory Flares In These People - Are...

Higher Body Temperature May Trigger Inflammatory Flares In These People – Are You At Risk?

Published on

The disease usually starts in early childhood, and people who have it often get high fevers, rashes, ulcers, swollen lymph nodes, and pain in their stomachs.

A groundbreaking study sheds light on the inflammatory disorder mevalonate kinase deficiency and identifies novel therapeutic targets for this life-threatening condition.

New research from the Garvan Institute of Medical Research demonstrates how increases in core body temperature may trigger inflammatory flares in individuals with a rare genetic autoinflammatory condition.

Mevalonate kinase deficiency (MKD) is a recessive disorder caused by changes in the gene for mevalonate kinase, an enzyme that is found in every cell in the body.

In the absence of this enzyme, abnormal proteins accumulate, causing immune system cells to malfunction and produce inflammation.

The disease usually starts in early childhood, and people who have it often get high fevers, rashes, ulcers, swollen lymph nodes, and pain in their stomachs.

A very serious illness can be fatal and also contribute to neurological and developmental issues.

“Our research provides exciting new insights into the underlying physiology of MKD,” says professor Mike Rogers, adding, “and what may be triggering the inflammatory flares, opening up potential new ways of treating this devastating disorder.”

The study appears in the Journal of Clinical Investigation.

Understanding MKD, and specifically what triggers disease flares in MKD patients, has made relatively little progress. One of the main reasons for this lack of knowledge is that there aren’t enough good animal models to study how diseases work, says the study’s lead author, Dr. Marcia Munoz of Garvan.

The group created new mouse models that mimic the metabolic mutation found in MKD patients using gene editing techniques.

“An increase in core body temperature, for example, which could occur with stress or a mild infection, worsened the impact of the mutant enzyme and led to a dramatic build-up of abnormal proteins. This is a likely cause of the inflammatory flares in patients,” adds Dr. Munoz.

It is unclear why MKD has a wide range of illness severity. It is challenging to forecast whether mutations together result in a mild or severe variant of MKD because the disease is brought on by having two copies of the mutant gene, according to Professor Rogers. There are more than 250 identified mutations.

Researchers created illness models with varying combinations of mutations, resulting in enzyme activities of 10% or 20% of normal.

“We discovered that there’s a threshold of enzyme activity. At about 20% activity, there is no disease. Disease starts to appear if enzyme activity falls below this threshold, when the effect on proteins really kicks in,” adds Professor Rogers.

Mice with 20% enzyme activity exhibited relatively modest illness, whereas those with 10% activity exhibited overt disease symptoms and larger quantities of aberrant proteins.

Notably, increasing the body temperature lowered enzyme activity to almost nearly zero, which led to very high amounts of the abnormal proteins.

“We can start to use this information predictively; for example, by measuring the level of abnormal proteins in samples of blood we may be able to foresee the severity of the symptoms” adds Professor Rogers. “Clinicians could use this knowledge to help diagnose and manage the disease.”

Importantly, the researchers found that NLRP3, a protein, participates in the inflammatory stage of MKD. The development of NLRP3 blockers for use in the clinic is currently of great interest due to its involvement in a wide range of inflammatory illnesses. Based on this finding, it seems like NLRP3 could be a new way to treat MKD.

Natalie Billiard, a parent of a 13-year-old daughter who has a rare autoinflammatory illness for which she received a diagnosis as a newborn, is pleased with the new findings. 

“Fifty years ago my daughter’s illness was termed ‘not compatible with life’. We have come a long way thanks to people like Professor Rogers and the research his team is doing. It’s giving our kids a chance at life,” she says.

Image Credit: Getty

You were reading: Higher Body Temperature May Trigger Inflammatory Flares In These People – Are You At Risk?

Latest articles

Most-complete Fossils Reveal New Horrifying Secrets Of Early Tetrapod – ‘T. Rex Of Its Time’

The Field Museum in Chicago has the largest and most complete remains of a...

New Research Finds ‘Striking’ Changes In The Brains Of Obese Children

New findings presented today show how higher weight and BMI can destroy the brain...

Eating This Popular Veggie Can Really Help if You’re Trying to Lose Weight – New Study

Trouble Losing Weight? Scientists agree that vegetables are an excellent source of many necessary...

Surprising New Findings: This Is What Actually Connects Us To Octopus

Animals with sophisticated neurological systems, such as cephalopods like octopuses, squids, and cuttlefish, are...

More like this

Most-complete Fossils Reveal New Horrifying Secrets Of Early Tetrapod – ‘T. Rex Of Its Time’

The Field Museum in Chicago has the largest and most complete remains of a...

New Research Finds ‘Striking’ Changes In The Brains Of Obese Children

New findings presented today show how higher weight and BMI can destroy the brain...

Eating This Popular Veggie Can Really Help if You’re Trying to Lose Weight – New Study

Trouble Losing Weight? Scientists agree that vegetables are an excellent source of many necessary...