R2IGH: Immunoglobulin Gene Rearrangement and Repair in Healthy Donors

Sponsor

University Hospital, Limoges (Other)

Overall Status

Completed

CT.gov ID

NCT04889573

Collaborator

(none)

120

Enrollment

Location

Arm

3.3

Actual Duration (Months)

36.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

B-cells ensure humoral immune response against antigens (Ag) thanks to their receptor (BCR). V(D)J rearrangement, somatic hypermutation, immunoglobulin (Ig) class switch and locus suicide recombination are mutational/recombinational processes targeting Ig loci influencing BCR expression. Study of these events is essential for B cell function analysis. Our project will provide the normal reference values using high throughput sequencing-based protocols.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Genetic: Blood sample	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Immunoglobulin Gene Rearrangement and Repair in Healthy Donors

Actual Study Start Date :

Jul 7, 2021

Actual Primary Completion Date :

Oct 14, 2021

Actual Study Completion Date :

Oct 14, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Blood sample	Genetic: Blood sample The blood samples will be collected from healthy volunteers : 7 tubes of 7 ml with anti-coagulant Héparine Lithium and 1 tube of 7ml with anti-coagulant EDTA

Arm

Intervention/Treatment

Experimental: Blood sample

Genetic: Blood sample

The blood samples will be collected from healthy volunteers : 7 tubes of 7 ml with anti-coagulant Héparine Lithium and 1 tube of 7ml with anti-coagulant EDTA

Outcome Measures

Primary Outcome Measures

Frequency of use of the V, D and J genes in VDJ rearrangements [through study completion, an average of 18 months]

Secondary Outcome Measures

Percentage of HyperMutation Somatic (SHM) in VDJ regions [through study completion, an average of 18 months]
Nature of HyperMutation Somatic (SHM) [through study completion, an average of 18 months]
transitions and transversions
Ig class switching (CSR) and recombination suicide of the IgH locus (LSR) junctions [through study completion, an average of 18 months]
number of CSR and LSR junctions
Frequency of g class switching (CSR) and recombination suicide of the IgH locus (LSR) junctions [through study completion, an average of 18 months]
frequency of CSR and LSR junctions according to their structure

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

healthy volunteers aged between 18 and 70
volunteers free from lymphoid hemopathy, immune deficiency and autoimmune disease.

3 categories : volunteers between 18 and 34 years of age, volunteers between 35 and 50 years of age, volunteers between 51 and 69 years of age.

Exclusion Criteria:

any recent vaccination (< 4 weeks)
tumoral pathology
lymphoïd hemopathy
immune deficiency
autoimmune disease
transplanted patients
inflammatory / systemic diseases
hypersensitivity or allergies
treatments likely to modify the immune response :
calcineurin inhibitors: ciclosporin, tacrolimus -antimetabolite: azathioprine, mycophenolate mofetil / mycophenolic acid, 6-mercaptopurine, methotrexate
cyclophosphamide
antilymphocyte serum (rabbit, horse)
mTOR inhibitors: everolimus, sirolimus
anti-CD25 (anti IL2-R): basiliximab, dacliximab -belatacept (anti CD80-86)
abatacept (CTLA4-Ig)
OKT3 (Muronomab-CD3, anti-CD23)
glucocorticoids: methylprednisolone, prednisone, prednisolone.
entuzumab (anti-CD52)
rituximab, ocrelizumab (anti-CD20)
eculizumab (anti-C5)
anakinra (analogue IL1-RA)
leflunomide (dihydroorotate dehydrogenase inhibition)
bortezomib (proteasome inhibitor)
fingolimod (S1P receptor antagonist)
alentuzumab (anti CD52)
Ig G -antiTNF (etanercept, infliximab, adalimumab, certolizumab)
vedolizumab (Anti-integrin α4β7 Ab)
ustekinumab (anti-IL12)
natalizumab (anti-integrin a4)
mitoxantrone (topoisomerase type II inhibitor)
tocilizumab (anti-IL6)