Absence of IL-6 Receptor Blockade Effect on the Outcomes of Transplant Glomerulopathy in the Absence of Anti-HLA Donor-specific Antibodies

Alberto Mella, MD, PhD; Antonio Lavacca, MD; Diana Teodora Dodoi, MD; Roberto Presta, MD; Fabrizio Fop, MSc; Marco Campagna, MD; Ana Maria Manzione, MD; Caterina Dolla, MD, PhD; Ester Gallo, MD; Isabella Abbasciano, MD; Chiara Gai, PhD; Giovanni Camussi, MD; Antonella Barreca, MD, PhD; Cristiana Caorsi, PhD; Gloria Giovinazzo, MD; Luigi Biancone, MD, PhD

doi:10.1097/TXD.0000000000001638

Transplantation Direct (Jun 2024)

Absence of IL-6 Receptor Blockade Effect on the Outcomes of Transplant Glomerulopathy in the Absence of Anti-HLA Donor-specific Antibodies

Alberto Mella, MD, PhD,
Antonio Lavacca, MD,
Diana Teodora Dodoi, MD,
Roberto Presta, MD,
Fabrizio Fop, MSc,
Marco Campagna, MD,
Ana Maria Manzione, MD,
Caterina Dolla, MD, PhD,
Ester Gallo, MD,
Isabella Abbasciano, MD,
Chiara Gai, PhD,
Giovanni Camussi, MD,
Antonella Barreca, MD, PhD,
Cristiana Caorsi, PhD,
Gloria Giovinazzo, MD,
Luigi Biancone, MD, PhD

Affiliations

Alberto Mella, MD, PhD: 1 Renal Transplantation Center, “A. Vercellone,” Division of Nephrology Dialysis and Transplantation, Città Della Salute e Della Scienza Hospital and Department of Medical Sciences, University of Turin, Turin, Italy.
Antonio Lavacca, MD: 1 Renal Transplantation Center, “A. Vercellone,” Division of Nephrology Dialysis and Transplantation, Città Della Salute e Della Scienza Hospital and Department of Medical Sciences, University of Turin, Turin, Italy.
Diana Teodora Dodoi, MD: 1 Renal Transplantation Center, “A. Vercellone,” Division of Nephrology Dialysis and Transplantation, Città Della Salute e Della Scienza Hospital and Department of Medical Sciences, University of Turin, Turin, Italy.
Roberto Presta, MD: 1 Renal Transplantation Center, “A. Vercellone,” Division of Nephrology Dialysis and Transplantation, Città Della Salute e Della Scienza Hospital and Department of Medical Sciences, University of Turin, Turin, Italy.
Fabrizio Fop, MSc: 1 Renal Transplantation Center, “A. Vercellone,” Division of Nephrology Dialysis and Transplantation, Città Della Salute e Della Scienza Hospital and Department of Medical Sciences, University of Turin, Turin, Italy.
Marco Campagna, MD: 1 Renal Transplantation Center, “A. Vercellone,” Division of Nephrology Dialysis and Transplantation, Città Della Salute e Della Scienza Hospital and Department of Medical Sciences, University of Turin, Turin, Italy.
Ana Maria Manzione, MD: 1 Renal Transplantation Center, “A. Vercellone,” Division of Nephrology Dialysis and Transplantation, Città Della Salute e Della Scienza Hospital and Department of Medical Sciences, University of Turin, Turin, Italy.
Caterina Dolla, MD, PhD: 1 Renal Transplantation Center, “A. Vercellone,” Division of Nephrology Dialysis and Transplantation, Città Della Salute e Della Scienza Hospital and Department of Medical Sciences, University of Turin, Turin, Italy.
Ester Gallo, MD: 1 Renal Transplantation Center, “A. Vercellone,” Division of Nephrology Dialysis and Transplantation, Città Della Salute e Della Scienza Hospital and Department of Medical Sciences, University of Turin, Turin, Italy.
Isabella Abbasciano, MD: 1 Renal Transplantation Center, “A. Vercellone,” Division of Nephrology Dialysis and Transplantation, Città Della Salute e Della Scienza Hospital and Department of Medical Sciences, University of Turin, Turin, Italy.
Chiara Gai, PhD: 2 Department of Medical Sciences, University of Turin, Turin, Italy.
Giovanni Camussi, MD: 2 Department of Medical Sciences, University of Turin, Turin, Italy.
Antonella Barreca, MD, PhD: 3 Division of Pathology, “Città Della Salute e Della Scienza” Hospital, Department of Medical Sciences, University of Turin, Turin, Italy.
Cristiana Caorsi, PhD: 4 Immunogenetic and Transplant Biology Center, “Città Della Salute e Della Scienza” Hospital and Department of Medical Sciences, University of Turin, Turin, Italy.
Gloria Giovinazzo, MD: 1 Renal Transplantation Center, “A. Vercellone,” Division of Nephrology Dialysis and Transplantation, Città Della Salute e Della Scienza Hospital and Department of Medical Sciences, University of Turin, Turin, Italy.
Luigi Biancone, MD, PhD: 1 Renal Transplantation Center, “A. Vercellone,” Division of Nephrology Dialysis and Transplantation, Città Della Salute e Della Scienza Hospital and Department of Medical Sciences, University of Turin, Turin, Italy.

DOI: https://doi.org/10.1097/TXD.0000000000001638
Journal volume & issue: Vol. 10, no. 6
p. e1638

Abstract

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Background. Transplant glomerulopathy (TG) is the hallmark of chronic antibody-mediated rejection but often occurs without anti-HLA donor-specific antibodies (DSAs) in the assumption that other DSAs may be the effectors of the tissue injury. Recently, we reported a positive effect of interleukin-6 (IL-6) receptor blocker tocilizumab (TCZ) in TG/DSA+. In the present study, we investigate the effect of TCZ in a cohort of TG cases without detectable anti-HLA DSAs. Methods. Single-center retrospective analysis of TG cases without anti-HLA DSAs (TG/DSA) treated with TCZ for chronic antibody-mediated rejection as first-line therapy evaluated through clinical, protocol biopsies, and gene expression analyses was included. Results. Differently from TG/DSA+, TG/DSA– showed a progressive reduction in the estimated glomerular filtration rate at 12 mo and after that with no significant modification in microvascular inflammation or C4d+. No upregulation in tight junction protein-1, aldo-keto reductase family 1 member C3, and calcium/calmodulin-dependent serine protein kinase, documented in TG/DSA+, was noted in post-TCZ biopsies. The reduction of microvascular inflammation was associated with natural killer-cell reduction in TG/DSA+, whereas TG/DSA– tends to maintain or increase periglomerular/interstitial infiltration. Conclusions. In the absence of anti-HLA DSAs, TG behavior seems not to be modified by IL-6 receptor blockade. These results are at variance with observational studies and previous trials with IL-6 inhibitors in TG associated with anti-HLA DSAs. These data may fuel the hypothesis of different mechanisms underlying TGs (including the potentially different roles of natural killer cells) and suggest carefully selecting patients with TG for clinical trials or off-label treatment based on their antidonor serologic status.

Published in Transplantation Direct

ISSN: 2373-8731 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://journals.lww.com/transplantationdirect/Pages/default.aspx

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