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临床试验/NCT03861962
NCT03861962尚未招募不适用

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

Assistance Publique - Hôpitaux de Paris0 个研究点目标入组 20,000 人开始时间: 2019年5月最近更新:
适应症

试验速览

阶段
不适用
状态
尚未招募
入组人数
20,000
主要终点
Proportion of serum-specific donor antibodies (DSA)

研究概览

简要总结

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.

研究设计

研究类型
Observational
观察模型
Cohort
时间视角
Retrospective

入排标准

年龄范围
7 Years 至 —(Child, Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • 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

排除标准

  • no inclusion if one of the inclusion criteria is not met

结局指标

主要结局

Proportion of serum-specific donor antibodies (DSA)

时间窗: at 2 years after organ transplantation

Proportion of serum-specific donor antibodies (DSA) regarding epitope mismatches

次要结局

  • Proportion of non-DSA anti-HLA antibodies(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(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(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(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(at 8 years after organ transplantation)
  • Proportion of dnDSA anti-HLA(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(at 8 years after organ transplantation)
  • Survival of the graft(at 8 years after organ transplantation)
  • Overall survival(at 8 years after organ transplantation)

研究者

申办方类型
Other
责任方
Sponsor

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