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

26 april 2019 bijgewerkt door: Assistance Publique - Hôpitaux de Paris

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.

Studie Overzicht

Toestand

Nog niet aan het werven

Studietype

Observationeel

Inschrijving (Verwacht)

20000

Contacten en locaties

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Studiecontact

Studie Contact Back-up

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

7 jaar en ouder (Kind, Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Bemonsteringsmethode

Niet-waarschijnlijkheidssteekproef

Studie Bevolking

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

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Proportion of serum-specific donor antibodies (DSA)
Tijdsspanne: at 2 years after organ transplantation
Proportion of serum-specific donor antibodies (DSA) regarding epitope mismatches
at 2 years after organ transplantation

Secundaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Proportion of dnDSA anti-HLA
Tijdsspanne: at 2 years after organ transplantation
at 2 years after organ transplantation
Proportion of dnDSA anti-HLA
Tijdsspanne: at 5 years after organ transplantation
at 5 years after organ transplantation
Proportion of dnDSA anti-HLA
Tijdsspanne: at 8 years after organ transplantation
at 8 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
Tijdsspanne: at 2 years after organ transplantation
at 2 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
Tijdsspanne: at 5 years after organ transplantation
at 5 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
Tijdsspanne: at 8 years after organ transplantation
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
Tijdsspanne: at 2 years after organ transplantation
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
Tijdsspanne: at 5 years after organ transplantation
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
Tijdsspanne: at 8 years after organ transplantation
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
Tijdsspanne: at 2 years after organ transplantation
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
Tijdsspanne: at 5 years after organ transplantation
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
Tijdsspanne: at 8 years after organ transplantation
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
Tijdsspanne: at 2 years after organ transplantation
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
Tijdsspanne: at 5 years after organ transplantation
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
Tijdsspanne: at 8 years after organ transplantation
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
Tijdsspanne: at 2 years after organ transplantation
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
Tijdsspanne: at 5 years after organ transplantation
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
Tijdsspanne: at 8 years after organ transplantation
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
Tijdsspanne: at 2 years after organ transplantation
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
Tijdsspanne: at 5 years after organ transplantation
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
Tijdsspanne: at 8 years after organ transplantation
at 8 years after organ transplantation
Survival of the graft
Tijdsspanne: at 5 years after organ transplantation
at 5 years after organ transplantation
Survival of the graft
Tijdsspanne: at 8 years after organ transplantation
at 8 years after organ transplantation
Overall survival
Tijdsspanne: at 5 years after organ transplantation
at 5 years after organ transplantation
Overall survival
Tijdsspanne: at 8 years after organ transplantation
at 8 years after organ transplantation

Medewerkers en onderzoekers

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Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Verwacht)

1 mei 2019

Primaire voltooiing (Verwacht)

1 mei 2019

Studie voltooiing (Verwacht)

1 mei 2025

Studieregistratiedata

Eerst ingediend

1 maart 2019

Eerst ingediend dat voldeed aan de QC-criteria

4 maart 2019

Eerst geplaatst (Werkelijk)

5 maart 2019

Updates van studierecords

Laatste update geplaatst (Werkelijk)

29 april 2019

Laatste update ingediend die voldeed aan QC-criteria

26 april 2019

Laatst geverifieerd

1 februari 2019

Meer informatie

Termen gerelateerd aan deze studie

Plan Individuele Deelnemersgegevens (IPD)

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ONBESLIST

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

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Klinische onderzoeken op DNA sequencing called "new generation" (or NGS)

3
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