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Case Reports
. 2025 May:274:110460.
doi: 10.1016/j.clim.2025.110460. Epub 2025 Feb 22.

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

Dajana Margeta  1 , Hirotsugu Noguchi  1 , Sepideh Khazaie  1 , Leal C Herlitz  2 , Joshua J Augustine  3 , Peter S Heeger  4 , Anat R Tambur  5 , Robert L Fairchild  1 , William M Baldwin 3rd  6
Affiliations
Case Reports

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

Dajana Margeta et al. Clin Immunol. 2025 May.

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.

Keywords: Antibody-mediated rejection; C4d staining; Digital spatial profiling; HLA class II antigens; Macrophages; Podocytes.

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Conflict of interest statement

Declaration of competing interest All the authors declared no competing interests.

References

    1. Zimmerman SM, Fropf R, Kulasekara BR, Griswold M, Appelbe O, Bahrami A, Boykin R, Buhr DL, Fuhrman K, Hoang ML, Huynh Q, Isgur L, Klock A, Kutchma A, Lasley AE, Liang Y, McKay-Fleisch J, Nelson JS, Nguyen K, Piazza E, Rininger A, Zollinger DR, Rhodes M, Beechem JM, Spatially resolved whole transcriptome profiling in human and mouse tissue using digital spatial profiling, Genome Res. 32 (2022) 1892–1905. - PMC - PubMed
    1. Lake BB, Menon R, Winfree S, Hu Q, Melo Ferreira R, Kalhor K, Barwinska D, Otto EA, Ferkowicz M, Diep D, Plongthongkum N, Knoten A, Urata S, Mariani LH, Naik AS, Eddy S, Zhang B, Wu Y, Salamon D, Williams JC, Wang X, Balderrama KS, Hoover PJ, Murray E, Marshall JL, Noel T, Vijayan A, Hartman A, Chen F, Waikar SS, Rosas SE, Wilson FP, Palevsky PM, Kiryluk K, Sedor JR, Toto RD, Parikh CR, Kim EH, Satija R, Greka A, Macosko EZ, Kharchenko PV, Gaut JP, Hodgin JB, Consortium K, Eadon MT, Dagher PC, El-Achkar TM, Zhang K, Kretzler M, Jain S, An atlas of healthy and injured cell states and niches in the human kidney, Nature 619 (2023) 585–594. - PMC - PubMed
    1. Mengel M, Loupy A, Haas M, Roufosse C, Naesens M, Akalin E, Clahsen-van Groningen MC, Dagobert J, Demetris AJ, Duong van Huyen JP, Gueguen J, Issa F, Robin B, Rosales I, Von der Thusen JH, Sanchez-Fueyo A, Smith RN, Wood K, Adam B, Colvin RB, Banff 2019 Meeting report: molecular diagnostics in solid organ transplantation-consensus for the Banff human organ transplant (B-HOT) gene panel and open source multicenter validation, Am. J. Transplant. 20 (2020) 2305–2317. - PMC - PubMed
    1. Nankivell BJ, P’Ng CH, Shingde M, Glomerular C4d Immunoperoxidase in chronic antibody-mediated rejection and transplant Glomerulopathy, Kidney Int. Rep. 7 (2022) 1594–1607. - PMC - PubMed
    1. Molne J, Nasic S, Brocker V, Stegmayr B, Felldin M, Peters B, Glomerular macrophage index (GMI) in kidney transplant biopsies is associated with graft outcome, Clin. Transpl. 36 (2022) e14816. - PMC - PubMed

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