Chronic Granulomatous Disease
Conditions
Keywords
inflammatory bowel disease, chronic granulomatous disease, inborn errors of immunity
Brief summary
ABSTRACT Introduction Residual or absent oxidase function in peripheral neutrophils may point to an inborn defect of neutrophil function - chronic granulomatous disease (CGD) - whereas low to normal oxidative burst capacity has been linked to variants in various members of the NADPH-complex. Aims To assess the clinical value of routinely measuring oxidative burst activity of granulocytes in pediatric patients diagnosed with very early onset IBD (VEO-IBD) and late onset IBD. Objectives To investigate possible correlations between neutrophil function and IBD disease activity and to inquire the presence of genetic variants in those with low to absent oxidative burst. To identify the rate of monogenic VEO-IBD in our cohort. Materials and Methods The proposal constitutes a collaborative effort among Romanian pediatric tertiary care centers to examine the value of assessing neutrophil function in all pediatric IBD patients. Children aged \<18 years diagnosed with Crohn's disease, ulcerative colitis or IBD-undetermined and age-matched healthy controls are recruited. A DHR flow cytometry assay is performed in included subjects and controls. Reduced or absent burst activity will lead to genetic testing in search of overt immunodeficiency or susceptibility variants. All VEO-IBD patients will have an immunological work-up in search of a primary immunodeficiency. Expected Results We anticipate to include a number of 150 pediatric patients with IBD over 12 months from the three pediatric gastroenterology units in Bucharest, Romania. We expect to identify an overall diminished neutrophil function in IBD patients versus controls and possible variants in the NADPH-complex genes.
Interventions
DIAGNOSTIC_TESTPhagoburst
The main objective is to perform oxidative burst activity in pediatric patients with a definitive diagnosis of IBD and compare them with healthy controls.
DIAGNOSTIC_TESTLymphocytes subsets
To determine lymphocytes subsets in patients with suspicion of IEI
DIAGNOSTIC_TESTGenetic testing
Perform targeted genetic testing in those with reduced to absent oxidative activity in search of PIDs and susceptibility variants
Sponsors
Marie Curie Emergency Children's Hospital, Bucharest
Victor Gomoiu Children's Hospital, Bucharest
National Institute for Mother and Child Health Alessandrescu Rusescu
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
Subjects: 1. age under 18 years; 2. confirmed diagnosis of IBD fulfilling standard diagnosis criteria (clinical, radiological, endoscopical, histological features) 3. parental/guardian consent for study enrollment Controls: Healthy age-gender matched controls
Exclusion criteria
1. IBD associated to an already defined monogenic defect 2. Diagnosis of IBD uncertain 3. HIV/TB positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oxidative burst activity in IBD patients | 12 months | Perform oxidative burst activity in pediatric patients with a definitive diagnosis of IBD and compare them with healthy controls. |
| Genetic testing in patients with suspicion of IEI | 12 months | Perform targeted genetic testing in those with reduced to absent oxidative activity in search of PIDs and susceptibility variants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Role of burst activity in disease phenotype | 12 months | Find correlations between burst activity and disease activity |
Countries
Romania
Contacts
Primary ContactAlexis Virgil Cochino, MD, PhD
Outcome results
None listed