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Review
. 2021 Apr 15:12:651222.
doi: 10.3389/fphar.2021.651222. eCollection 2021.

Therapies for Chronic Allograft Rejection

Affiliations
Review

Therapies for Chronic Allograft Rejection

Min Young Kim et al. Front Pharmacol. .

Abstract

Remarkable advances have been made in the pathophysiology, diagnosis, and treatment of antibody-mediated rejection (ABMR) over the past decades, leading to improved graft outcomes. However, long-term failure is still high and effective treatment for chronic ABMR, an important cause of graft failure, has not yet been identified. Chronic ABMR has a relatively different phenotype from active ABMR and is a slowly progressive disease in which graft injury is mainly caused by de novo donor specific antibodies (DSA). Since most trials of current immunosuppressive therapies for rejection have focused on active ABMR, treatment strategies based on those data might be less effective in chronic ABMR. A better understanding of chronic ABMR may serve as a bridge in establishing treatment strategies to improve graft outcomes. In this in-depth review, we focus on the pathophysiology and characteristics of chronic ABMR along with the newly revised Banff criteria in 2017. In addition, in terms of chronic ABMR, we identify the reasons for the resistance of current immunosuppressive therapies and look at ongoing research that could play a role in setting better treatment strategies in the future. Finally, we review non-invasive biomarkers as tools to monitor for rejection.

Keywords: antibody formation; antirejection therapy; graft rejection; kidney transplantation; transplantation immunology.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Immune mechanisms of graft rejection and therapeutic targets.Plasma exchange (PE) and intravenous immunoglobulin (IVIG) remove DSAs. Anti-CD20 monoclonal antibody (mAb) eliminates B cells, memory B cells, and short-lived plasma cells (PC). However, PE, IVIG, and anti-CD20 mAb are insufficient to inhibit long-lived PCs that continuously produce antibodies. Although proteasome inhibitors (PI), bortezomib and carfilzomib, can eliminate PCs, the expansion of bortezomib-induced germinal center (GC) B cells and Tfh cells or the appearance of carfilzomib-resistant bone marrow PCs may mitigate the effect of PI. Anti-CD38 mAb depletes PCs, but it can also suppress T regulatory (Treg) cells. Combination strategies using costimulation blockers, anti-interleukin 6 (IL-6), and anti-B-cell-activating factor (BAFF) mAB could further enhance the effectiveness of rejection therapies in blocking antibody production and preventing graft damage by generating synergy of the drugs.

References

    1. Abuzeineh M., Tariq A., Rosenberg A., Brennan D. C. (2020). Chronic active antibody-mediated rejection following COVID-19 infection in a kidney transplant recipient: a case report. Transplant. Proc., S0041-1345 (20), 32898. 10.1016/j.transproceed.2020.10.050 - DOI - PMC - PubMed
    1. Amrouche L., Aubert O., Suberbielle C., Rabant M., Van Huyen J.-P. D., Martinez F., et al. (2017). Long-term outcomes of kidney transplantation in patients with high levels of preformed DSA. Transplantation 101 (10), 2440–2448. 10.1097/tp.0000000000001650 - DOI - PubMed
    1. Anglicheau D., Naesens M., Essig M., Gwinner W., Marquet P. (2016). Establishing biomarkers in transplant medicine. Transplantation 100 (10), 2024–2038. 10.1097/tp.0000000000001321 - DOI - PubMed
    1. Aubert O., Loupy A., Hidalgo L., Duong Van Huyen J.-P., Higgins S., Viglietti D., et al. (2017). Antibody-mediated rejection due to preexisting versusDe NovoDonor-specific antibodies in kidney allograft recipients. Jasn 28 (6), 1912–1923. 10.1681/asn.2016070797 - DOI - PMC - PubMed
    1. Bachelet T., Nodimar C., Taupin J. L., Lepreux S., Moreau K., Morel D., et al. (2015). Intravenous immunoglobulins and rituximab therapy for severe transplant glomerulopathy in chronic antibody-mediated rejection: a pilot study. Clin. Transpl. 29 (5), 439–446. 10.1111/ctr.12535 - DOI - PubMed

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