Immunoglobulin Gene Rearrangement and Repair in Healthy Donors (R2IGH)

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Genetic: Blood sample

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Limoges, France, 87200
    • Limoges University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome 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 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

Collaborators and Investigators

• Sponsor: University Hospital, Limoges

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2021
• Primary Completion (Actual): October 14, 2021
• Study Completion (Actual): October 14, 2021

Study Registration Dates

• First Submitted: May 5, 2021
• First Submitted That Met QC Criteria: May 14, 2021
• First Posted (Actual): May 17, 2021

Study Record Updates

• Last Update Posted (Actual): October 19, 2021
• Last Update Submitted That Met QC Criteria: October 18, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: CSR; BCR; Ig; LSR; normal values; B-cells; VDJ rearrangement; SHM; HTS
• Other Study ID Numbers: 87RI20_0074 (R2IGH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No