Clinical trial NCT03633409: Differential EBI2 Expression Upon Allelic Status of the rs9557195 Polymorphism
Official title: Differential EBI2 Expression Upon Allelic Status of the rs9557195 Polymorphism
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Inflammatory Bowel Diseases
Keywords: IBD
EBI2
G protein coupled receptor
FACS
UBAC2
lymphocyte migration
single nucleotide polymorphism
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2018-08-16
Enrollment: 340
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: we will recruit a mixed population (patients can be in more than one group)

* up to 100 healthy volunteers
* up to 30 IBD patients with the rs9557195-CC IBD risk genotype in clinical remission
* up to 30 IBD patients with the rs9557195-CT IBD risk genotype in clinical remission
* up to 30 IBD patients with the rs9557195-TT IBD low risk genotype in clinical remission
* up to 50 IBD patients of any genotype during a flare
* up to 50 IBD patients of any genotype treated with vedolizumab
* up to 50 IBD patients of any genotype treated with a TNF-inhibitor (infliximab, adalimumab, golimumab, certolizumab)

Brief summary: EBI2 is a risk gene for inflammatory bowel diseases (rs9557195). Patients of the Swiss IBD cohort study have been genotyped for the allelic status of EBI2. The investigators will test the influence of rs9557195 genoty (TT or CC allel), inflammatory activity and current treatment (infliximab vs. vedolizumab) on expression and activity of EBI2 on blood lymphocytes, mRNA expression of EBI2 and UBAC2 (located on the opposite DNA strand of EBI2) and activity of lymphocytes on a migraton assay.

Detailed description: EBI2 is a risk gene for inflammatory bowel diseases (rs9557195). EBI2 is a G protein coupled receptors expressed on the immune cells. EBI2 directs migration and activity of immune cells.

Patients of the Swiss IBD cohort study have been genotyped for the allelic status of EBI2. The investigators will recruit patients with Crohn's disease and ulcerative colitis, assess epidemiological and clinical parameters (including clinical activity of IBD) draw blood, isolate lymphocytes, DNA and RNA.

The investigators will test the influence of rs9557195 genotype (TT or CC allel), inflammatory activity and current treatment (infliximab vs. vedolizumab) on expression and activity of EBI2 on blood lymphocytes (by FACS using an EBI2-antibody), mRNA expression (by qPCR) of EBI2 and UBAC2 (located on the opposite DNA strand of EBI2) and activity of lymphocytes on a migration assay.

Eligibility criteria: Inclusion Criteria:

* Patient with IBD OR healthy volunteer
* No major uncontrolled medical/ surgical/ psychiatric condition requiring ongoing management besides IBD in the respective study groups. Well controlled conditions (i.e. medically controlled arterial hypertension, occupational asthma) may be present

Exclusion Criteria: none

Primary outcomes:
measure: EBI2 expression - dependent on rs9557195 allele status (FACS)
timeFrame: at time of inclusion into the study
Secondary outcomes:
measure: EBI2 expression - dependent on rs9557195 allele status (RT-PCR)
timeFrame: at time of inclusion into the study
measure: UBAC2 expression - dependent on rs9557195 allele status (RT-PCR)
timeFrame: at time of inclusion into the study
measure: Motility of PBMCs dependent on rs9557195 allele status (Boyden chamber)
timeFrame: at time of inclusion into the study
measure: EBI2-expression (FACS) in individuals treated with infliximab vs. vedolizumab
timeFrame: at time of inclusion into the study
measure: EBI2-expression (FACS) according to gut inflammation
timeFrame: at time of inclusion into the study
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
References: