Patients with Fanconi anemia (FA) may demonstrate a substantial increase in serum serotonin levels 2 weeks after hematopoietic stem cell transplantation (HSCT), according to study results published in Blood Advances.
FA is a condition involving defective DNA repair that gives rise to bone marrow abnormalities and a propensity to malignancies, but patients with FA also commonly display metabolic disturbances. In this study, the researchers set out to explore various aspects of tryptophan metabolism in the context of FA.
“In this report, we describe for the first time multiple tryptophan-related metabolic abnormalities in individuals with FA undergoing bone marrow transplant,” the study authors wrote in their report.
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The research team performed enzyme-linked immunosorbent assays on tryptophan and metabolites in blood and stool specimens obtained through the Cincinnati Children’s Hospital Medical Center in Ohio, from a total of 23 patients with FA and 29 patients with other diagnoses. Transcript, immunohistochemistry, and nuclear magnetic resonance assays were also performed for multiple gene expression and metabolite analyses.
Serum tryptophan levels were elevated in patients in this study 14 days after HSCT, regardless of diagnosis. Levels of serum serotonin, a tryptophan metabolite, also were significantly altered in patient at 14 days following transplantation; however, a substantial increase in serotonin was primarily found in patients with FA (P <.0001), while most patients with other diagnoses showed a decrease during this time (P =.019).
While serum serotonin showed increases in patients with FA following HSCT, the opposite pattern emerged in these patients for serotonin present in stool, which showed a decrease at 14 days (P =.0026); patients with other diagnoses also showed a decrease in stool serotonin (P =.0001). However, the researchers separately found that serotonin was present in skin samples in patients with FA, but not in age-matched control subjects, suggesting possible differences in the sites and associated impacts of serotonin production in patients with FA.
Additionally, the researchers detected an inverse correlation between serum serotonin levels and body-mass index in patients with FA (Spearman’s correlation coefficient, -0.51; P =.013). Because of the effects of serotonin on an array of biological processes, including appetite reduction and others, the researchers suggested serotonin itself may be a therapeutic target in FA treatment.
“Our findings suggest serotonin inhibition as a new avenue to diminish a multitude of clinical risks and disease phenotypes in FA, which will now require detailed characterization of local and systemic serotonin metabolism,” the researchers concluded in their report.
Reference
Bartlett AL, Romick-Rosendale L, Nelson A, et al. Tryptophan metabolism is dysregulated in individuals with Fanconi anemia. Blood Adv. 2021;5(1):250-261. doi:10.1182/bloodadvances.2020002794
