Metabolites Linked to Nourishment, Inflammation Altered in RDEB

Changes in amino acids seen in recessive dystrophic epidermolysis bullosa

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Patients with recessive dystrophic epidermolysis bullosa (RDEB) had distinct blood metabolic profiles compared with healthy people, a study showed.

The most significantly altered molecules were amino acids — the building blocks of proteins — most of which were at lower levels in RDEB patients and correlated with disease severity.

Many observed changes were linked to malnutrition and inflammation, two features of RDEB, whereas changes linked to fibrosis (scarring) were not evident as expected, the researchers noted.

The study, “Plasma metabolomic profiling reflects the malnourished and chronic inflammatory state in recessive dystrophic epidermolysis bullosa,” was published in the Journal of Dermatological Science.

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Patients with RDEB have two mutated copies of the COL7A1 gene — one inherited from each biological parent. COL7A1 encodes for a portion of the type VII collagen protein, which is important for giving structure and support to the skin and other tissues.

As a result, RDEB patients have fragile skin that easily blisters and scars. The condition is also marked by other features, including systemic inflammation and malnutrition.

Metabolomics is the study of small molecules, called metabolites, that are produced in the process of cellular activities. Metabolomics has emerged as a way to identify distinct biomarkers associated with disease progression or a disease’s particular clinical features.

Metabolic analysis and its results

The researchers conducted a metabolomic analysis of the blood from RDEB patients and healthy people to identify such biomarkers for the rare genetic condition.

Participants were recruited from the National Cheng Kung University Hospital in Taiwan and included 10 patients and 10 healthy controls. Of RDEB patients, seven had severe disease and three had intermediate.

Blood samples were taken and analyzed for metabolites, and all participants were interviewed by a dietitian to document weight, calorie and protein intake, and use of nutritional supplements or medications.

Patients had significantly lower body weight and body mass index (BMI) compared with healthy participants, despite most patients having adequate estimated daily caloric intakes. Low body weight correlated with clinical disease severity.

Metabolic analyses showed distinct profiles between RDEB patients and healthy participants. Patients with intermediate disease severity had a profile that overlapped somewhat with both healthy people and severe patients, suggesting that metabolic profiles may also correlate with disease severity, the researchers noted.

The class of metabolites that most significantly differed between the groups was amino acids. In general, a majority of amino acids and some of their downstream products were at lower levels in RDEB patients compared with healthy people. These amino acid decreases were associated with increased RDEB clinical severity.

Observed metabolic changes were linked to processes involved in malnutrition and inflammation.

While some amino acid levels correlated with body weight in RDEB patients, they did not correlate with weight in healthy controls.

Low amino acid levels have been observed in other conditions of malnourishment or growth delay, and the finding could reflect the chronic malnourished state of RDEB patients, the team noted.

“The general downregulation of amino acid levels in RDEB may be explained by both malnutrition as well as increased amino acid exhaustion and nitrogen loss due to chronic inflammation,” the researchers hypothesized.

One amino acid in particular, called glutamine, was reduced in RDEB patients. Glutamine plays a number of roles in the body, including to provide fuel to the gut to aid digestion, easing inflammation and promoting wound healing.

“To the best of our knowledge, glutamine supplementation in RDEB has not been investigated, but our data indicate this may be a worthwhile endeavor,” the researchers wrote.

Other amino acids linked to inflammatory processes, including tryptophan and phenylalanine, were also altered in the RDEB patients, likely reflecting chronic inflammation. Accumulation of succinate, a metabolite that typically accumulates in inflammatory conditions, was found in RDEB patients.

While certain changes in metabolites linked to fibrosis were expected in RDEB patients, observed changes were not as predicted, based on observations from other diseases marked by fibrosis.

“The systemic dysregulation of metabolites in RDEB reflects malnutrition and chronic inflammation while, unexpectedly, fibrosis-related metabolic characteristics are less apparent,” the researchers wrote.

“Several metabolites, particularly amino acids, merit further study as potential biomarkers of disease severity in RDEB,” the team concluded.