Study finds elevated inflammatory markers in Fabry patients

Early markers could help indicate onset, progression of organ dysfunction

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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People with Fabry disease have higher-than-normal levels of three inflammatory markers in their blood, according to a recent study.

These markers include elevated neopterin and biopterin levels, and an increased kynurenine-to-tryptophan ratio.

The study, “Serum Neopterin, Biopterin, Tryptophan, and Kynurenine Levels in Patients with Fabry Disease,” was published in the Balkan Medical Journal.

Fabry disease is caused by mutations in the gene that provides instructions for making the enzyme alpha-galactosidase A. This enzyme is a key component of lysosomes, which are cellular structures that act as “recycling centers,” helping to break down unneeded molecules. Without a functional version of this enzyme, certain fatty molecules such as lyso-Gb3 build up to toxic levels in cells, causing damage that drives disease symptoms.

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Increased immune inflammation in dysfunctional lysosomes

In addition to helping remove cellular waste, lysosomes are also important for the function of the immune system. These cellular compartments play critical roles in allowing immune cells to identify and eliminate infectious threats. Prior studies have suggested immune inflammation is increased when the lysosome is dysfunctional in conditions like Fabry disease.

In the study, a team of scientists in Turkey evaluated levels of three inflammatory markers in the blood, comparing levels seen in 33 people diagnosed with Fabry against levels from 33 people without the disease who were matched by age and sex. Most of the Fabry patients were on enzyme replacement therapy.

The first two inflammatory markers assessed were neopterin and biopterin, both of which belong to a class of inflammation-related molecules called pteridines. Neopterin is produced by cells of the immune system when they are activated, while biopterin is involved in the production of neurotransmitters and plays a role in maintaining immune system balance.

Results showed average levels of both these markers were significantly increased in Fabry patients. The ratio of neopterin to biopterin also tended to be higher in Fabry patients — which could indicate increased activity of the immune system or inflammation — though the difference from controls wasn’t statistically significant.

The third marker measured in the study was kynurenine, which is a molecular byproduct made when tryptophan (an amino acid, one of the building blocks of proteins) is broken down. Kynurenine levels tended to be increased in Fabry patients, while tryptophan levels tended to be decreased. Neither of these differences was statistically significant on its own, but the ratio of kynurenine to tryptophan was significantly higher in Fabry patients than in those without the disease.

The researchers noted increased levels of these inflammatory markers were seen in Fabry patients even very early in the disease course, and in patients with or without treatment.

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Higher levels of neopterin linked to heart, kidney issues

Further statistical analyses showed Fabry patients with higher levels of biopterin or kynurenine tended also to have lower lyso-Gb3 levels, but these trends weren’t statistically significant.

However, analyses did show patients with higher levels of neopterin were more likely to have heart problems such as abnormal heart rhythms or an enlarged heart (a common sign of heart damage). Patients with higher neopterin levels also tended to have poorer kidney health.

Meanwhile, higher levels of kynurenine were linked with a greater likelihood of problems affecting the valves of the heart, and higher tryptophan levels were associated with an increased risk of hearing issues.

Collectively, these results suggest “pteridine and kynurenine metabolites may serve as early biomarkers of inflammation in Fabry disease, indicating the onset and progression of organ dysfunction,” the researchers wrote, adding that in addition to ERT, “targeted therapies for inflammation and immune activation may be beneficial in managing the disease.”

They noted, however, that this study was limited by its small size and the fact that these markers were assessed at only one point in time, and called for more long-term studies to investigate the potential utility of these inflammatory markers in larger populations.