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. 2020 Aug;34(8):e13908.
doi: 10.1111/ctr.13908. Epub 2020 Jun 16.

Early effects of first-line treatment with anti-interleukin-6 receptor antibody tocilizumab for chronic active antibody-mediated rejection in kidney transplantation

Antonio Lavacca  1 , Roberto Presta  1 , Chiara Gai  2 , Alberto Mella  1 , Ester Gallo  1 , Giovanni Camussi  2 , Isabella Abbasciano  1 , Antonella Barreca  3 , Cristiana Caorsi  4 , Fabrizio Fop  1 , Maria Messina  1 , Maura Rossetti  1 , Luigi Biancone  1
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Free article

Early effects of first-line treatment with anti-interleukin-6 receptor antibody tocilizumab for chronic active antibody-mediated rejection in kidney transplantation

Antonio Lavacca et al. Clin Transplant. 2020 Aug.
Free article

Abstract

Introduction: Chronic active antibody-mediated rejection (cAMR) is a major determinant of late allograft failure. Rituximab/immunoglobulins (IVIg) + plasma exchange (PLEX) showed controversial results in cAMR treatment. Tocilizumab (TCZ), a humanized anti-interleukin 6 receptor antibody, has been recently used as rescue therapy in patients non-responsive to rituximab/IVIg/PLEX with favorable outcomes. Whether TCZ acts "per se" or requires a priming effect from previous treatments is currently unknown.

Methods: Fifteen patients with cAMR were treated with TCZ as a first-line therapy and followed for a median time of 20.7 months.

Results: Despite the majority of patients experiencing advanced transplant glomerulopathy (TG) at diagnosis (60% with cg3), glomerular filtration rate and proteinuria stabilized during the follow-up, with a significant reduction in donor-specific antibodies. Protocol biopsies after 6 months demonstrated significant amelioration of microvascular inflammation and no TG, C4d deposition, or IF/TA progression. Gene-expression and immunofluorescence analysis showed upregulation of three genes (TJP-1, AKR1C3, and CASK) involved in podocyte, mesangial, and tubular restoration.

Conclusion: Tocilizumab adopted as a first-line approach in cAMR was associated with early serological and histological improvements and functional stabilization even in advanced TG, suggesting a role for the use of TCZ alone with the avoidance of unnecessary previous immunosuppressants.

Keywords: angiotensin II type I-receptor antibody; anti-HLA antibody; chronic antibody-mediated rejection; donor-specific antibodies; kidney transplantation; tocilizumab; transplant glomerulopathy.

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References

REFERENCES

    1. Loupy A, Hill GS, Jordan SC. The impact of donor-specific anti-HLA antibodies on late kidney allograft failure. Nat Rev Nephrol. 2012;8(6):348-357.
    1. Billing H, Rieger S, Ovens J, et al. Successful treatment of chronic antibody-mediated rejection with IVIG and rituximab in pediatric renal transplant recipients. Transplantation. 2008;86(9):1214-1221.
    1. Fehr T, Rüsi B, Fischer A, Hopfer H, Wüthrich RP, Gaspert A. Rituximab and intravenous immunoglobulin treatment of chronic antibody-mediated kidney allograft rejection. Transplantation. 2009;87(12):1837-1841.
    1. Hong YA, Kim HG, Choi SR, et al. Effectiveness of rituximab and intravenous immunoglobulin therapy in renal transplant recipients with chronic active antibody-mediated rejection. Transplant Proc. 2012;44(1):182-184.
    1. Smith RN, Malik F, Goes N, et al. Partial therapeutic response to Rituximab for the treatment of chronic alloantibody mediated rejection of kidney allografts. Transpl Immunol. 2012;27(2-3):107-113.

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