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Updated: Jun 18, 2026
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Mouse Model of Alloimmune-induced Vascular Rejection and Transplant Arteriosclerosis
Published on: May 17, 2015
Spatial Analysis Identifies Endothelial HLA-F as a Prognostic Marker in Antibody-mediated Rejection.
Toshihito Hirai1, Tomokazu Shimizu2, Hironori Fukuda1
1Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.
Transplantation
|June 16, 2026
Summary
Human Leukocyte Antigen-F (HLA-F) is a novel biomarker for antibody-mediated rejection (ABMR) in kidney transplants. Its expression in the peritubular capillary niche correlates with rejection severity and predicts kidney function decline.
Area of Science:
- Immunology
- Transplantation Biology
- Genomics
Background:
- Microvascular injury (MVI) is crucial for diagnosing antibody-mediated rejection (ABMR) in kidney allografts but lacks prognostic value.
- Previous work linked CD31+ endothelial cells and CD68+ macrophages in the peritubular capillary (PTC) niche to graft outcomes.
- Understanding the molecular basis of this cellular interaction is key to improving ABMR diagnosis and management.
Purpose of the Study:
- To investigate the molecular mechanisms driving cellular interactions within the PTC niche in kidney allografts.
- To identify novel molecular markers associated with antibody-mediated rejection (ABMR) and its severity.
- To explore the potential of spatial transcriptomics for discovering biomarkers in kidney transplantation.
Main Methods:
- Spatial transcriptomic profiling using GeoMx Digital Spatial Profiler on CD31+ and CD68+ regions within the PTC niche.
- Discovery cohort analysis of 3 ABMR and 3 T cell-mediated rejection (TCMR) samples using whole-transcriptome atlas sequencing.
- Validation cohort analysis of 67 kidney allograft biopsies (42 ABMR, 25 non-ABMR) using immunohistochemistry for Human Leukocyte Antigen-F (HLA-F).
Main Results:
- A coordinated interferon-γ-driven transcriptional program was identified in both CD31+ and CD68+ cells in ABMR samples.
- Human Leukocyte Antigen-F (HLA-F) emerged as a prominent feature, significantly associated with MVI severity and donor-specific antibody positivity.
- Higher HLA-F expression in active ABMR patients correlated with a greater decline in kidney function post-biopsy.
Conclusions:
- Human Leukocyte Antigen-F (HLA-F) is identified as a novel molecular marker associated with ABMR pathogenesis.
- HLA-F expression within the PTC niche shows potential as a prognostic biomarker for kidney allograft outcomes.
- Spatially resolved analysis of the PTC niche offers valuable insights into ABMR mechanisms and biomarker discovery.
