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

Assistance Publique - Hôpitaux de Paris

Status: Not yet enrolling

Conditions: Organ Transplantation

Treatments: Other: DNA sequencing called "new generation" (or NGS)

Study type: Observational

Funder types: Other

Identifiers

NCT03861962

NI16035HLJ

Details and patient eligibility

About

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.

Enrollment: 20,000 estimated patients

Sex: All

Ages: 7+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• no inclusion if one of the inclusion criteria is not met