Th1, Th2, Th17 Phenotype in Urea Cycle Disorders

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Th1, Th2, Th17 Phenotype in Urea Cycle Disorders

Conditions
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Urea Cycle Disorder, Lysinuric Protein Intolerance

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 53 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with urea cycle disorder<br>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<br>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<br>Children without any comorbidity and chronic diseases. | |

What is the study measuring?
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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 |