Organ Transplantation
Conditions
Keywords
serum-specific donor antibodies (DSA), human leukocyte antigens (HLA), organ allocation, epitope level
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.
Interventions
OTHERDNA sequencing called new generation (or NGS)
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
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
7 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of serum-specific donor antibodies (DSA) | at 2 years after organ transplantation | Proportion of serum-specific donor antibodies (DSA) regarding epitope mismatches |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of non-DSA anti-HLA antibodies | at 2 years after organ transplantation |
| Proportion of both total and HLA class I or class II dnDSA by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1) , by HLA antigen, by epitope, for all types of organs and by organ type | at 2 years after organ transplantation |
| Number of dnDSA anti-HLA both total and by HLA class (class I versus class II), by HLA locus (A, B, C, DRB1, DRB3 / 4/5, DQB1, DQA1, DPB1, DPA1), by HLA antigen, for all organ types and organ type | at 2 years after organ transplantation |
| Distribution of anti-HLA dnDSA by targeted epitope and antigen (to define immunodominant and non-immunodominant epitopes and antigens), both total and by HLA class (class I versus class II), by HLA locus for all types of organs and organ type | at 2 years after organ transplantation |
| Proportion of dnDSA anti-HLA | at 2 years after organ transplantation |
| Strength in mean fluorescence intensity of dnDSA anti-HLA de novo specific epitopes of epitopes DQbeta, DQalpha and composites (DQbeta + DQalpha) by antigen DQ | at 2 years after organ transplantation |
| Survival of the graft | at 5 years after organ transplantation |
| Overall survival | at 5 years after organ transplantation |
| Distribution of strength anti-HLA dnDSA measured by mean fluorescence intensity to identify the immunodominant DSA, both global and by class, by HLA locus by HLA antigen, by epitope, for all types of organs and organ type | at 2 years after organ transplantation |
Contacts
Primary ContactJean-Luc TAUPIN, Pr
Backup ContactSylvie Chevret, Pr
Outcome results
None listed