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

Organ Transplantation Clinical Trial

— ACORG-HLA  

Official title:

Re-evaluation of Donor-specific Anti-HLA Alloantibodies Immunoassay After Organ Transplantation, From Antigen Level to Epitope Level: a Track to Improve Organ Allocation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03861962
• Other study ID #: NI16035HLJ
• Status: Not yet recruiting
• Start date: May 2019
• Est. completion date: May 2025

Study information

• Verified date: February 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Jean-Luc TAUPIN, Pr
• Phone: +331 42 49 90 81
• Email: jean-luc.taupin[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20000
• Est. completion date: May 2025
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Organ Transplantation

Intervention

Other:
• DNA 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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of serum-specific donor antibodies (DSA)	Proportion of serum-specific donor antibodies (DSA) regarding epitope mismatches	at 2 years after organ transplantation
Secondary	Proportion of dnDSA anti-HLA		at 2 years after organ transplantation
Secondary	Proportion of dnDSA anti-HLA		at 5 years after organ transplantation
Secondary	Proportion of dnDSA anti-HLA		at 8 years after organ transplantation
Secondary	Proportion of non-DSA anti-HLA antibodies		at 2 years after organ transplantation
Secondary	Proportion of non-DSA anti-HLA antibodies		at 5 years after organ transplantation
Secondary	Proportion of non-DSA anti-HLA antibodies		at 8 years after organ transplantation
Secondary	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
Secondary	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 5 years after organ transplantation
Secondary	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 8 years after organ transplantation
Secondary	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
Secondary	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 5 years after organ transplantation
Secondary	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 8 years after organ transplantation
Secondary	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
Secondary	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 5 years after organ transplantation
Secondary	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 8 years after organ transplantation
Secondary	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
Secondary	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 5 years after organ transplantation
Secondary	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 8 years after organ transplantation
Secondary	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
Secondary	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 5 years after organ transplantation
Secondary	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 8 years after organ transplantation
Secondary	Survival of the graft		at 5 years after organ transplantation
Secondary	Survival of the graft		at 8 years after organ transplantation
Secondary	Overall survival		at 5 years after organ transplantation
Secondary	Overall survival		at 8 years after organ transplantation