Organ TransplantationACORG-HLANCT03861962
Re-evaluation of Donor-specific Anti-HLA Alloantibodies Immunoassay After Organ Transplantation, From Antigen Level to Epitope Level
An observational study of Organ Transplantation, run by Assistance Publique - Hôpitaux de Paris.
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… Read more about this study
- Who is it for?
- Ages 7 years and older
- Conditions the study is for
- Organ Transplantation
- What is being tested?
- DNA sequencing called "new generation" (or NGS)
- How many people
- 20,000 participants
- Where
- No sites listed yet
- Study dates
- May 2019to May 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
Who may be able to join
- 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
Who cannot join
- no inclusion if one of the inclusion criteria is not met
Trial locations and contacts
No sites are listed yet.
About this study
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
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
- Being tested
- DNA sequencing called "new generation" (or NGS)
- Keywords
- serum-specific donor antibodies (DSA), human leukocyte antigens (HLA), organ allocation, epitope level
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of serum-specific donor antibodies (DSA)
Proportion of serum-specific donor antibodies (DSA) regarding epitope mismatches
Measured: at 2 years after organ transplantation
Secondary outcomes (25)
Proportion of dnDSA anti-HLA
Measured: at 2 years after organ transplantation
Proportion of dnDSA anti-HLA
Measured: at 5 years after organ transplantation
Proportion of dnDSA anti-HLA
Measured: at 8 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
Measured: at 2 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
Measured: at 5 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
Measured: at 8 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
Measured: 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
Measured: at 5 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
Measured: at 8 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
Measured: 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
Measured: at 5 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
Measured: at 8 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
Measured: 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
Measured: at 5 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
Measured: at 8 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
Measured: at 2 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
Measured: 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
Measured: at 8 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
Measured: 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
Measured: at 5 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
Measured: at 8 years after organ transplantation
Survival of the graft
Measured: at 5 years after organ transplantation
Survival of the graft
Measured: at 8 years after organ transplantation
Overall survival
Measured: at 5 years after organ transplantation
Overall survival
Measured: at 8 years after organ transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2019
- Study startMay 2019 (estimated)
- Primary completionMay 2019 (estimated)
- Study completionMay 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Organ TransplantationStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 20,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03861962
- Sponsor's protocol ID
- NI16035HLJ
- Acronym
- ACORG-HLA
- Status last verified
- Feb 2019
- First submitted
- 1 Mar 2019
- Last updated
- 29 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Usureau C, Siemowski J, Anglicheau D, Leon J, Matignon M, Snanoudj R, Lefaucheur C, Francois H, Grimbert P, Durrbach A, Hertig A, Jalal-Eddine A, Louis K, Mohamadou I, Hogan J, Boyer O, Letort V, Taupin JL. Optimizing risk-benefit in highly sensitized kidney recipient antigen delisting increasing donor access. Kidney Int. 2026 Aug;110(2):477-482. doi: 10.1016/j.kint.2026.04.023. Epub 2026 May 25.
PubMed 42191114Lhotte R, Murphey C, Tafulo S, Turner D, Usureau C, Devriese M; SFHI Consortium; Letort V, Taupin JL. Evaluating the Antigen and Eplet Accuracy of DQA1 Imputations With the HaploSFHI Two-Field HLA Typing Inference Tool. HLA. 2025 Apr;105(4):e70197. doi: 10.1111/tan.70197.
PubMed 40269614
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03861962
- Acronym / sponsor ID
- ACORG-HLA / NI16035HLJ
- Conditions
- Organ Transplantation
- Keywords
- serum-specific donor antibodies (DSA), human leukocyte antigens (HLA), organ allocation, epitope level
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20,000 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- May 2019 (estimated)
- Primary completion
- May 2019 (estimated)
- Study completion
- May 2025 (estimated)
- First posted
- 5 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (1 listed)
- no inclusion if one of the inclusion criteria is not met
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Other | – |
Primary outcome
Proportion of serum-specific donor antibodies (DSA)
Time frame: at 2 years after organ transplantation
Proportion of serum-specific donor antibodies (DSA) regarding epitope mismatches
25 secondary outcomes
Proportion of dnDSA anti-HLA
Time frame: at 2 years after organ transplantation
Proportion of dnDSA anti-HLA
Time frame: at 5 years after organ transplantation
Proportion of dnDSA anti-HLA
Time frame: at 8 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
Time frame: at 2 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
Time frame: at 5 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
Time frame: at 8 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
Time frame: 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
Time frame: at 5 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
Time frame: at 8 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
Time frame: 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
Time frame: at 5 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
Time frame: at 8 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
Time frame: 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
Time frame: at 5 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
Time frame: at 8 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
Time frame: at 2 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
Time frame: 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
Time frame: at 8 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
Time frame: 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
Time frame: at 5 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
Time frame: at 8 years after organ transplantation
Survival of the graft
Time frame: at 5 years after organ transplantation
Survival of the graft
Time frame: at 8 years after organ transplantation
Overall survival
Time frame: at 5 years after organ transplantation
Overall survival
Time frame: at 8 years after organ transplantation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2019.
- Derived from this study: PubMed 42191114Usureau C, Siemowski J, Anglicheau D, Leon J, Matignon M, Snanoudj R, Lefaucheur C, Francois H, Grimbert P, Durrbach A, Hertig A, Jalal-Eddine A, Louis K, Mohamadou I, Hogan J, Boyer O, Letort V, Taupin JL. Optimizing risk-benefit in highly sensitized kidney recipient antigen delisting increasing donor access. Kidney Int. 2026 Aug;110(2):477-482. doi: 10.1016/j.kint.2026.04.023. Epub 2026 May 25.
- Derived from this study: PubMed 40269614Lhotte R, Murphey C, Tafulo S, Turner D, Usureau C, Devriese M; SFHI Consortium; Letort V, Taupin JL. Evaluating the Antigen and Eplet Accuracy of DQA1 Imputations With the HaploSFHI Two-Field HLA Typing Inference Tool. HLA. 2025 Apr;105(4):e70197. doi: 10.1111/tan.70197.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
An observational study of Organ Transplantation, run by Assistance Publique - Hôpitaux de Paris.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jean-Luc TAUPIN, Pr (+331 42 49 90 81, jean-luc.taupin@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of serum-specific donor antibodies (DSA) (time frame: at 2 years after organ transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03861962, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2019.