Spatial transcriptomics of Glomerulo-centric antibody mediated rejection in renal transplants

IF 4.5 3区医学 Q2 IMMUNOLOGY

Clinical immunology Pub Date : 2025-02-22 DOI:10.1016/j.clim.2025.110460

Dajana Margeta , Hirotsugu Noguchi , Sepideh Khazaie , Leal C. Herlitz , Joshua J. Augustine , Peter S. Heeger , Anat R. Tambur , Robert L. Fairchild , William M. Baldwin III

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Abstract

In this case study, we used Digital Spatial Profiling to localize transcripts in a series of 4 biopsies from a single patient before, during and after treatment for acute antibody-mediated rejection that was characterized by strong C4d staining of the glomeruli. Spatial resolution demonstrated that molecular signatures of innate immune cells including NK cells and macrophages are located in glomeruli during AMR, and transcripts for HLA class II antigens were upregulated in the glomeruli. In contrast, transcripts of signature genes for podocytes were decreased during rejection. Treatment with IVIg resolved histological evidence of glomerulitis but did not restore expression of podocyte transcripts. These data demonstrate a vulnerability of podocytes in acute AMR with persistent glomerulitis. Additionally, by using a protocol biopsy from the same patient as a baseline, transcript changes for an informative set of genes were uncovered to test for podocyte dysfunction in future patients.

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来源期刊

Clinical immunology 医学-免疫学

CiteScore

12.30

自引率

1.20%

发文量

212

审稿时长

34 days

期刊介绍： Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.