Healthy Volunteers
Conditions
Keywords
B-cells, BCR, VDJ rearrangement, SHM, CSR, LSR, Ig, HTS, normal values
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.
Interventions
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
Sponsors
Study design
Eligibility
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency of use of the V, D and J genes in VDJ rearrangements | through study completion, an average of 18 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
France