Amino Acid Metabolism and Immune Dysfunction in Urea Cycle Disorders: T and B Cell Perspectives

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dc.authoridGemici Karaaslan, Betul/0000-0002-0303-7146
dc.authoridKiykim, Ayca/0000-0001-5821-3963
dc.authoridAktuglu Zeybek, Ayse Cigdem/0000-0001-7256-0750
dc.contributor.authorKaraaslan, Betul Gemici
dc.contributor.authorKiykim, Ayca
dc.contributor.authorBurtecene, Nihan
dc.contributor.authorGokden, Meltem
dc.contributor.authorCansever, Mehmet Serif
dc.contributor.authorHopurcuoglu, Duhan
dc.contributor.authorCengiz, Gokce Nuran
dc.date.accessioned2025-04-06T12:23:57Z
dc.date.available2025-04-06T12:23:57Z
dc.date.issued2025
dc.departmentTekirdağ Namık Kemal Üniversitesi
dc.description.abstractUrea cycle disorders (UCDs) are a group of genetic metabolic conditions characterized by enzyme deficiencies responsible for detoxifying ammonia. Hyperammonemia, the accumulation of intermediate metabolites, and a deficiency of essential amino acids-due to a protein-restrictive diet and the use of ammonia scavengers-can increase the risk of infections, particularly during metabolic crises. While the underlying mechanisms of immune suppression are still being fully elucidated, hyperammonemia may impair the function of immune cells, particularly T cells and macrophages, inhibiting the proliferation of T cells and cytokine production. Arginine, which is essential for T-cell activation and function, may also be limited in these patients, and its depletion can increase their vulnerability to infections. Twenty-four UCD patients and 31 healthy donors were recruited for the study. Peripheral lymphocyte subset analysis, intracellular protein and cytokine staining, and proliferation assays were performed by flow cytometry. Amino acid levels were measured using the HPLC method. The UCD patients exhibited low lymphocyte-proliferation capacity in both proximal and distal defects in response to phytohaemagglutinin (PHA) and anti-CD2, anti-CD3, and anti-CD28 (CD-mix), which was lower than healthy controls. Proximal-UCD patients exhibited a significantly higher response for IFN-gamma compared to both distal-UCD patients and healthy controls. The different amino acids in the culture medium were changed significantly in the groups. This study highlights significant immune dysfunctions in UCD patients, particularly impaired T-cell proliferation and altered amino acid metabolism. Proximal UCD patients exhibited a higher IFN-gamma response, indicating a potential for hyperinflammation. Despite this, infection rates did not significantly differ between proximal UCD and distal UCD patients, although distal UCD patients had higher hospitalization rates. Amino acid analysis revealed distinct metabolic disruptions, emphasizing the complex interplay between metabolism and immune function. These findings suggest that UCDs cause profound immune alterations, necessitating further research to develop targeted therapeutic strategies.
dc.description.sponsorshipScientific Research Projects Coordination Unit of Istanbul University-Cerrahpasa [TOA-2021-35251]
dc.description.sponsorshipThis study was funded by the Scientific Research Projects Coordination Unit of Istanbul University-Cerrahpasa. Project number TOA-2021-35251.
dc.identifier.doi10.1002/jimd.70009
dc.identifier.issn0141-8955
dc.identifier.issn1573-2665
dc.identifier.issue2
dc.identifier.pmid39957310
dc.identifier.scopus2-s2.0-85218058390
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1002/jimd.70009
dc.identifier.urihttps://hdl.handle.net/20.500.11776/17275
dc.identifier.volume48
dc.identifier.wosWOS:001422370400001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofJournal of Inherited Metabolic Disease
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250406
dc.subjecthyperammonemia
dc.subjectimmune dysfunction
dc.subjectT-cell proliferation
dc.subjecturea cycle disorders (UCD)
dc.titleAmino Acid Metabolism and Immune Dysfunction in Urea Cycle Disorders: T and B Cell Perspectives
dc.typeArticle

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