Diagnostic Value of Mass Spectrometry-based Proteomics in Microvascular Inflammation in Kidney Transplantation, the TranSpec Study.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 141
- 试验地点
- 6
- 主要终点
- Assessing diagnostic performance of tissue protein signature
研究概览
简要总结
Microvascular inflammation, the hallmark histological criteria of antibody-mediated rejection in kidney transplantation, remains an issue in routine practice, due to a lack of reproducibility in its recognition by pathologists and an incomplete comprehension of its pathophysiology, leading to a poor treatment efficacy. The main objective of this study is to assess the performances of tissue proteic signatures designed for the diagnosis of microvascular inflammation in kidney transplantation, from formalin-fixed and paraffin-embedded (FFPE) allograft biopsies analyzed by mass spectrometry-based proteomics.
详细描述
Antibody-mediated rejection (ABMR) is due to pathogenic antibodies produced by the donor (donor-specific antibodies, DSA) that are directed against Human Leukocyte Antigens (HLA) or other antigens (non HLA) of the graft. ABMR is currently the leading cause of long-term kidney allograft failure. Histological lesions of microvascular inflammation (MVI) are the hallmark criteria of ABMR according to the 2019 Banff classification. Lack of reproducibility in the scoring of MVI by pathologists is still an issue of the diagnosis of ABMR in routine practice, while the understood pathophysiological mechanisms of MVI (anti-HLA DSA, DSA against non HLA antigens and/or NK cell-mediated) are poorly assessed in practice, possibly explaining the wide variability of treatment efficacy. In a prior study, the investigators confirmed the value of mass spectrometry for the analysis of the glomerular proteome during ABMR, compared to the one of stable grafts, from FFPE biopsies. The investigators identified 82 proteins, particularly involved in leukocyte activation and the interferons pathways, in accordance with transcriptomic approaches. Five proteins were validated by immunohistochemistry.
The investigators now propose to analyze kidney allograft FFPE biopsies of 92 patients by mass spectrometry, including 32 with MVI (with and without anti-HLA DSA) and 60 with relevant differential diagnoses. The main objective is to assess the diagnostic performances of tissue proteic signatures designed by machine-learning methods for the diagnosis of microvascular inflammation, the reference standard being the 2019 Banff classification. One of the secondary objectives includes the comparison of the protein profile of MVI with and without anti-HLA DSA, but also the proteomic analysis of 60 urine samples from the same population, in order to assess the performances of mass spectrometry in the non-invasive diagnosis of MVI in kidney transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Kidney transplant recipients
- •Diagnosis based on the 2019 Banff classification (polyomavirus nephropathy, T cell-mediated rejection, borderline changes)
- •Renal allograft biopsy allowing inclusion with at least 7 permeable glomeruli
- •The microvascular inflammation group with anti-HLA DSA is defined as follows:
- •At least moderate microvascular inflammation: g + ptc > 2
- •At least one anti-HLA DSA in the serum at the time of biopsy, with a Mean Fluorescence Intensity (MFI) > 3000 for the immunodominant DSA or the sum of the DSA
- •The microvascular inflammation group without anti-HLA DSA is defined as follows:
- •At least moderate microvascular inflammation: g + ptc > 2
- •No historical anti-HLA DSA or at the time of biopsy, MFI < 500
- •The stable graft recipients group is defined as follows:
- •Glomerual Filtration Rate > 40ml/min, without clinical proteinuria
- •No detectable DSA
- •Protocol biopsy at 1 year posttransplantation without specific lesion or nonspecific severe lesion
- •The chronic nonspecific graft changes group is defined as follows:
- •Moderate to severe interstitial fibrosis and tubular atrophy, in the absence of specific lesions: active rejection (antibody-mediated or T cell-mediated), borderline lesions, recurrent or de novo nephropathy, polyomavirus associated nephropathy.
- •No C4d deposits on peritubular capillaries
- •No detectable anti-HLA DSA at the time of biopsy.
- •The ischemic acute tubular injuries group is defined as :
- •Histological lesions of tubular injuries in the absence of significant microvascular inflammation or C4d deposits
- •No detectable anti-HLA DSA at the time of biopsy
排除标准
- •Minor patients
- •Mixed rejection (antibody-mediated and T cell-mediated)
- •Recurrent or de novo nephropathy
- •Specific treatment of rejection (T cell-mediated or antibody-mediated) in the last 6 months, excluding induction and
- •Baseline immunosuppressive treatment.
研究组 & 干预措施
Experimental
干预措施: Mass spectrometry-based proteomics of FFPE biopsies and urine samples (Diagnostic Test)
结局指标
主要结局
Assessing diagnostic performance of tissue protein signature
时间窗: 18 months after inclusion
The primary outcome is the sensitivity and specificity of tissue protein signature in the diagnosis of microvascular inflammation (MVI) in kidney transplantation, the diagnostic reference standard being based on the 2019 Banff classification (histological and biological criteria). This primary outcome is based on FFPE kidney allograft biopsies.
次要结局
- Assessing the diagnostic performance of urine protein signatures(18 months after inclusion)
- Assessing the performance of tissue proteomic signature(18 months after inclusion)
- Assessing the performance of urine proteomic signature(18 months after inclusion)
- Compare protein profiles observed within different phenotypes of MVI in kidney transplantation(18 months after inclusion)