Immunoglobulin Gene Rearrangement and Repair in Healthy Donors

Study Overview
=================
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.

Official Title
-----------------
Immunoglobulin Gene Rearrangement and Repair in Healthy Donors

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Genetic: Blood sample


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blood sample<br> | Genetic: Blood sample<br>* 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<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of use of the V, D and J genes in VDJ rearrangements |  | through study completion, an average of 18 months | 

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
B-cells, BCR, VDJ rearrangement, SHM, CSR, LSR, Ig, HTS, normal values