Clinical trial NCT04889573: Immunoglobulin Gene Rearrangement and Repair in Healthy Donors
Official title: Immunoglobulin Gene Rearrangement and Repair in Healthy Donors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Volunteers
Keywords: B-cells
BCR
VDJ rearrangement
SHM
CSR
LSR
Ig
HTS
normal values
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
First posted: 2021-05-17
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


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)

Primary outcomes:
measure: Frequency of use of the V, D and J genes in VDJ rearrangements
timeFrame: through study completion, an average of 18 months
Secondary outcomes:
measure: Percentage of HyperMutation Somatic (SHM) in VDJ regions
timeFrame: through study completion, an average of 18 months
measure: Nature of HyperMutation Somatic (SHM)
timeFrame: through study completion, an average of 18 months
measure: Ig class switching (CSR) and recombination suicide of the IgH locus (LSR) junctions
timeFrame: through study completion, an average of 18 months
measure: Frequency of g class switching (CSR) and recombination suicide of the IgH locus (LSR) junctions
timeFrame: through study completion, an average of 18 months
Other outcomes:
Locations:
city: Limoges
country: France
facility: Limoges University Hospital
Study officials:
References: