Th1, Th2, Th17 Phenotype in Urea Cycle Disorders

Infection-related hyperammonemia in patients with urea cycle disorders is an important cause of morbidity and mortality. The relationship between immune system cells and the metabolic pathways used by these cells and inborn errors of metabolism is still under investigation. Current studies are generally based on experiments in mice. The investigators' goal is to study specific T cell subsets to understand the effects of the urea cycle on T cells.

The investigators collected blood samples from participants with lysinuric protein intolerance and urea cycle disorders for basic immunophenotyping, lymphocyte proliferation in response to phytohemagglutinin and CDmix, and cytokine analysis involving Th1, Th2, and Th17 and compared them with age-matched healthy controls. They also examined amino acid profiles in sera and supernatants before and after stimulation with PMA-ionomycin.

Study Overview

• Status: Completed
• Conditions: Urea Cycle Disorder; Lysinuric Protein Intolerance

Detailed Description

The investigators aim to compare cellular immune response of T cell phenotype and proliferative functions in addition to lymphocyte subset analysis between urea cycle disorders and healthy controls.

Complete blood counts, immunoglobuline levels, lymptocyte subset analysis and Thelper cells will be analyzed. Additionally, T helper cells will be measured regarding their cytokine profile as Th1, Th2 and Th17. T cell proliferation response and aminoacid profiles in supernatants before and after stimulation will be measured.

• Study Type: Observational
• Enrollment (Actual): 65

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey, 34098
    • Istanbul University-Cerrahpasa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 53 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

patients with a diagnosis of urea cycle disorders and lysinuric protein intolerance

Description

Inclusion Criteria:

• Children without any chronic conditions and having normal immunoglobulins and lymphocyte subsets

Exclusion Criteria:

• For healthy control, children having any signs for primary immune deficiencies

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Patients with urea cycle disorder; Patients with inborn errors of metabolism resulting from defects in one of the enzymes or transporter molecules involved in the hepatic removal of ammonia from the bloodstream
Patients with lysinuric protein intolerance; Patients with disorder caused by the body's inability to digest and use certain protein building blocks (amino acids), namely lysine, arginine, and ornithine
Healthy control; Children without any comorbidity and chronic diseases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of Th1, Th2 and Th17 cells	Th1, Th2 and Th17 cells will be measured following stimulation in cell culture	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of T cell proliferative capacity	T cells' proliferation will be measured following stimulation in cell culture	baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of amino acid profile changes before and after stimulation	Serum Aminoacids from periphery, in cell culture supernatants before and after stimulation will be measured	baseline

Collaborators and Investigators

• Sponsor: Istanbul University - Cerrahpasa (IUC)
• Investigators: Principal Investigator: Ayca Kiykim, Istanbul University - Cerrahpasa (IUC)

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2021
• Primary Completion (Actual): December 13, 2022
• Study Completion (Actual): September 1, 2023

Study Registration Dates

• First Submitted: January 23, 2023
• First Submitted That Met QC Criteria: January 23, 2023
• First Posted (Actual): January 31, 2023

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Urea Cycle Disorders, Inborn
• Other Study ID Numbers: IFUCD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No