Re-evaluation of Donor-specific Anti-HLA Alloantibodies Immunoassay After Organ Transplantation, From Antigen Level to Epitope Level

NCT03861962 | Unknown

• 1 other identifier: NI16035HLJ
• Study Type: observational
• Target: 20,000
• Locations: 0 countries
• Sites: N/A

Brief Summary

Transplantation is the only treatment for end-stage organ dysfunction, with dialysis for the kidney. However, donor / recipient (D / R) tissue incompatibility accounts for the majority of long-term graft losses, through the development of serum-specific donor antibodies (DSA) to human leukocyte antigens (HLA) of donor, with a prevalence of about 10% at 2 years and 20% at 5 years. DSA immunization is very often directed against one or a few of the donor's incompatible antigens, suggesting that epitopes (and antigens) are not all equally immunogenic. Identifying HLA epitopes that cause the most and the least immunization would help refine the graft distribution to better manage a limited resource by defining the D / R combinations to avoid or promote. Since the immunogenicity of an HLA epitope depends on the HLA of the recipient given the properties of the epitopes mentioned above, a very large cohort is needed to understand this question. To do so, it is necessary to redo these typings with a method exploring all the genes (add DQA1, DRB3 / 4/5, DPB1 and DPA1) when this has not been done after the graft as part of the standard care. This has become possible since 3 years by DNA sequencing called "new generation" (or NGS), a method that is supplanting all others for the medical care of patients in transplantation. This study is a retrospective cohort study with 5-year follow-up. The investigators' main objective is to evaluate the predictive value of the number of mismatched HLA epitopes for the development of DSA anti-HLA de novo at 2 years. The investigators' secondary objectives are to evaluate this parameter at 5 and 8 years to determine which epitope mismatches should be favored / avoided in the future.

Conditions

Organ Transplantation

Keywords

serum-specific donor antibodies (DSA); human leukocyte antigens (HLA); organ allocation; epitope level

Outcome Measures

Primary Outcomes (1)

• Proportion of serum-specific donor antibodies (DSA)

  Proportion of serum-specific donor antibodies (DSA) regarding epitope mismatches

  at 2 years after organ transplantation

Secondary Outcomes (25)

• Proportion of dnDSA anti-HLA

  at 2 years after organ transplantation

• Proportion of dnDSA anti-HLA

  at 5 years after organ transplantation

• Proportion of dnDSA anti-HLA

  at 8 years after organ transplantation

• Proportion of non-DSA anti-HLA antibodies

  at 2 years after organ transplantation

• Proportion of non-DSA anti-HLA antibodies

  at 5 years after organ transplantation

Interventions

DNA sequencing called "new generation" (or NGS) OTHER

Redo HLA-typings with a method exploring all the genes (add DQA1, DRB3 / 4/5, DPB1 and DPA1), i.e. DNA sequencing called "new generation", when this has not been done after the graft as part of the standard care

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients (adults and children) récipients of a first kidney transplant / heart / lung / liver donor living or deceased,non-immunized anti-HLA before the transplant, having preserved their graft \> 2 years will be enrolled

You may qualify if:

• patients (adults and children)
• patients recipients in France from 2008 to 2015 of a first kidney transplant / heart / lung / liver donor living or deceased, non-immunized anti-HLA before the transplant
• patients having preserved their graft \> 2 years
• having agreed to the use for research purposes in transplantation of the remains of the DNA and serum samples taken as part of the care of which the remains are available

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Central Study Contacts

Jean-Luc TAUPIN, Pr

CONTACT

+331 42 49 90 81; jean-luc.taupin@aphp.fr

Sylvie Chevret, Pr

CONTACT

+33142499742; sylvie.chevret@paris7.jussieu.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2019
• First Posted: March 5, 2019
• Study Start: May 1, 2019
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2025
• Last Updated: April 29, 2019

Record last verified: 2019-02