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

2019年4月26日 更新者: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.

調査の概要

状態

まだ募集していません

条件

研究の種類

観察的

入学 (予想される)

20000

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

7年歳以上 (子、大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

サンプリング方法

非確率サンプル

調査対象母集団

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

説明

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

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

この研究は何を測定していますか?

主要な結果の測定

結果測定
メジャーの説明
時間枠
Proportion of serum-specific donor antibodies (DSA)
時間枠:at 2 years after organ transplantation
Proportion of serum-specific donor antibodies (DSA) regarding epitope mismatches
at 2 years after organ transplantation

二次結果の測定

結果測定
時間枠
Proportion of dnDSA anti-HLA
時間枠:at 2 years after organ transplantation
at 2 years after organ transplantation
Proportion of dnDSA anti-HLA
時間枠:at 5 years after organ transplantation
at 5 years after organ transplantation
Proportion of dnDSA anti-HLA
時間枠:at 8 years after organ transplantation
at 8 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
時間枠:at 2 years after organ transplantation
at 2 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
時間枠:at 5 years after organ transplantation
at 5 years after organ transplantation
Proportion of non-DSA anti-HLA antibodies
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠:at 8 years after organ transplantation
at 8 years after organ transplantation
Survival of the graft
時間枠:at 5 years after organ transplantation
at 5 years after organ transplantation
Survival of the graft
時間枠:at 8 years after organ transplantation
at 8 years after organ transplantation
Overall survival
時間枠:at 5 years after organ transplantation
at 5 years after organ transplantation
Overall survival
時間枠:at 8 years after organ transplantation
at 8 years after organ transplantation

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ここでは、この調査に関係する人々や組織を見つけることができます。

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (予想される)

2019年5月1日

一次修了 (予想される)

2019年5月1日

研究の完了 (予想される)

2025年5月1日

試験登録日

最初に提出

2019年3月1日

QC基準を満たした最初の提出物

2019年3月4日

最初の投稿 (実際)

2019年3月5日

学習記録の更新

投稿された最後の更新 (実際)

2019年4月29日

QC基準を満たした最後の更新が送信されました

2019年4月26日

最終確認日

2019年2月1日

詳しくは

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医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

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