Metabolites in blood tests may help diagnose HAE, study suggests
Measures of molecule levels able to differentiate angioedema types
HAE attacks
Changes in the levels of certain metabolites — molecules that take part in metabolism — in the blood may serve as accurate biomarkers to diagnose hereditary angioedema (HAE), a study suggests.
Moreover, ratios of metabolite levels also were able to differentiate between people with HAE and those with idiopathic angioedema, or angioedema without an identifiable cause.
“Identifying new biomarkers may offer enhanced prospects for accurate, timely, and economical diagnosis of HAE, as well as tailored treatment selection for optimal patient care,” the researchers wrote.
The study, “Exploring disease-specific metabolite signatures in hereditary angioedema patients,” was published in the journal Frontiers in Immunology.
Levels of metabolites in the blood may be ‘accurate’ biomarkers for HAE
HAE is a rare genetic disorder mostly caused by a deficient or dysfunctional enzyme called C1 esterase inhibitor, or C1-INH. In HAE types 1 and 2, a lack of functional enzyme triggers recurrent episodes of swelling attacks, called edema, in the deeper layers of the skin.
Blood levels and activity of C1-INH are used to diagnose HAE, as are levels of C4, a protein that’s broken down by another enzyme normally blocked by C1-INH. A diagnosis usually is confirmed by genetic testing to identify the disease-causing mutation(s).
Metabolomics is the study of all small-molecule metabolites found in blood, urine, or tissue. Due to advances in detection, the technique can now identify a wide range of metabolites using noninvasive or minimally invasive methods. It can be used to find biomarkers to help with diagnosis, monitor treatment responses, and understand disease processes.
“Exploring the metabolite profile of HAE, which is currently not well-defined, could lead to an improved comprehension of the disease’s underlying mechanisms and facilitate the identification of novel metabolic biomarkers,” according to the team of researchers, from Latvia.
Blood samples were collected from 10 patients with HAE type 1 or 2, 15 patients with idiopathic angioedema, and 20 healthy individuals who served as controls. Idiopathic angioedema was included to control factors that may influence the metabolome results. A set of 55 metabolites routinely tested during newborn screening were measured.
“By measuring these established markers, changes detected in their concentrations in HAE patients’ blood could potentially offer a readily implementable diagnostic tool for this inherited disorder,” the researchers wrote.
Experiments detected three metabolites that differed between both types of angioedema and the control group: cysteine, isovalerylcarnitine, and hydroxyproline. Cysteine and hydroxyproline are amino acids, or protein building blocks, while isovalerylcarnitine is the breakdown product of leucine, another amino acid.
By measuring these established markers, changes detected in their concentrations in HAE patients’ blood could potentially offer a readily implementable diagnostic tool for this inherited disorder.
Cysteine, which has antioxidant properties and plays a role in immune function, was markedly lower in HAE patients than in the control group, and isovalerylcarnitine, which is involved in the transport of fatty acids into cells, was lower in both angioedema groups.
Levels of another amino acid, called aspartic acid, were higher in HAE patients when compared with idiopathic angioedema patients, indicating that “aspartic acid is a significant metabolite that can differentiate between HAE and idiopathic [angioedema],” the team wrote.
A statistical analysis revealed that combining multiple metabolite results significantly improved the ability to predict HAE. Using the ratio of hydroxyproline times cysteine over creatinine times isovalerylcarnitine, the ability to correctly identify HAE was 100% (sensitivity), and the ability to rule out HAE was 90% (selectivity).
Likewise, the ratio of the amino acids glycine and asparagine distinguished HAE from idiopathic angioedema, with a sensitivity of 90% and a selectivity of 85.7%. The team noted that age had no significant effect on the altered levels of metabolites.
“Our results provide a valuable contribution to the HAE diagnosis and treatment field,” the researchers wrote. “The potential benefits of identifying new biomarkers and conducting further research with larger study groups are significant and could significantly improve the lives of patients affected by this rare disease.”
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