Pre-transplant CD45RC expression on blood T cells differentiates patients with cancer and rejection after kidney transplantation

Garnier, Antoine; Planchais, Martin; Riou, Jérémie; Jacquemin, Clément; Ordonez, Laurence; Saint‐André, Jean‐Paul; Croué, Anne; Saoudi, Abdelhadi; Delneste, Yves; Devys, Anne; Boutin, Isabelle; Subra, Jean‐François; Duveau, Agnès; Augusto, Jean-François

doi:10.1371/journal.pone.0214321

Cited by 7 publications

(11 citation statements)

References 29 publications

(50 reference statements)

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“…CD45RC is an isoform of CD45 that we showed to be expressed at least in both rats [3][4][5][6][7][8][9][10] and humans [11][12][13][14] at high levels in T cells (T CD45RC high ) precursors of Th1 as well as in terminally differentiated effector memory (TEMRA) cells that are responsible for acute solid organ rejection and aGVHD. Conversely, Th2 precursors as well as CD4 1 and CD8 1 Foxp3 1 Treg that are able to inhibit acute solid organ rejection and aGVHD are all CD45RC low/both in rats [3][4][5][6][7][8][9][10] and humans.…”

Section: Introductionmentioning

confidence: 81%

“…Conversely, Th2 precursors as well as CD4 1 and CD8 1 Foxp3 1 Treg that are able to inhibit acute solid organ rejection and aGVHD are all CD45RC low/both in rats [3][4][5][6][7][8][9][10] and humans. [11][12][13][14] In a solid organ transplantation fully MHC-incompatible rat model, we showed that a short course of anti-CD45RC mAb treatment induced preferential depletion of CD45RC high T cells leading to permanent allogeneic tolerance through the induction of activated donor-specific CD8 1 and CD4 1 Tregs. 9 In anti-CD45RC-treated animals, memory and de novo immune responses were preserved.…”

Section: Introductionmentioning

confidence: 99%

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Transient antibody targeting of CD45RC inhibits the development of graft-versus-host disease

et al. 2020

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Allogeneic bone marrow transplantation (BMT) is a widely spread treatment of many hematological diseases, but its most important side effect is graft-versus-host disease (GVHD). Despite the development of new therapies, acute GVHD (aGVHD) occurs in 30% to 50% of allogeneic BMT and is characterized by the generation of effector T (Teff) cells with production of inflammatory cytokines. We previously demonstrated that a short anti-CD45RC monoclonal antibody (mAb) treatment in a heart allograft rat model transiently decreased CD45RChigh Teff cells and increased regulatory T cell (Treg) number and function allowing long-term donor-specific tolerance. Here, we demonstrated in rat and mouse allogeneic GVHD, as well as in xenogeneic GVHD mediated by human T cells in NSG mice, that both ex vivo depletion of CD45RChigh T cells and in vivo treatment with short-course anti-CD45RC mAbs inhibited aGVHD. In the rat model, we demonstrated that long surviving animals treated with anti-CD45RC mAbs were fully engrafted with donor cells and developed a donor-specific tolerance. Finally, we validated the rejection of a human tumor in NSG mice infused with human cells and treated with anti-CD45RC mAbs. The anti-human CD45RC mAbs showed a favorable safety profile because it did not abolish human memory antiviral immune responses, nor trigger cytokine release in in vitro assays. Altogether, our results show the potential of a prophylactic treatment with anti-human CD45RC mAbs in combination with rapamycin as a new therapy to treat aGVHD without abolishing the antitumor effect.

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Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Transient antibody targeting of CD45RC inhibits the development of graft-versus-host disease

et al. 2020

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“…In their study from 2019, Garnier et al[ 85 ] examined the pretransplant populations of cluster of differentiation forty five isoform with alternative mRNA splicing of exon (CD45RC) T cells in 89 KTRs. CD45RC expression dictates either a more regulatory (low expression) phenotype or pro-inflammatory (high expression) phenotype.…”

Section: Novel Biomarker Classificationmentioning

confidence: 99%

“…CD45RC expression dictates either a more regulatory (low expression) phenotype or pro-inflammatory (high expression) phenotype. Intriguingly, they found that differences in these populations predicted opposing outcomes: KTRs with a low CD4+CD45RC high population (< 51.9%) carried a 3.7 fold risk of cancer [HR = 3.71 (95%CI: 1.24 to 11.1); P = 0.019] vs the high CD4+CD45 high population having a 20-fold higher risk of rejection [HR = 21.7 (95%CI: 2.67 to 176.2); P = 0.0004][ 85 ]. The results of these studies are illustrated in Table 10 .…”

Section: Novel Biomarker Classificationmentioning

confidence: 99%

Role of novel biomarkers in kidney transplantation

Swanson

Aziz

Garg

et al. 2020

WJT

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Clinical application of biomarkers is an integral component of transplant care. Clinicians and scientists alike are in search of better biomarkers than the current serologic (serum creatinine, donor-specific antibodies), urine-derived (urinalysis, urine protein), and histologic ones we now use. The science behind recent biomarker discovery spans across multiple molecular biologic disciplines, including transcriptomics, proteomics, and metabolomics. Innovative methodology and integration of basic and clinical approaches have allowed researchers to unearth molecular phenomena preceding clinical disease. Biomarkers can be classified in several ways. In this review, we have classified them via their origin and outcome: Primarily immunologic, i.e ., representative of immune regulation and dysfunction and non-immunologic, pertaining to delayed graft function, cardiovascular events/mortality, infection, malignancy, post-transplant diabetes, graft, and patient survival. Novel biomarker uses to guide the diagnosis and management of transplant-related outcomes is a promising area of research. However, the use of biomarkers to predict outcomes after kidney transplantation is not well studied. In this review, we summarize the recent studies illustrating biomarker use and transplant outcomes.

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“…We demonstrated in a previous work that the level of CD45RC expression at the surface of blood CD8 + T cells before kidney transplantation was associated with the risk of AR after transplantation [10,13]. This study was conducted on a cohort of 89 kidney transplant recipients transplanted between 1999 and 2004, and we observed that a pre-transplant proportion of CD8 + CD45RC high T cells above 54.7% conferred a 6-fold increased risk of developing AR after 4.8 years of follow-up [10].…”

Section: Introductionmentioning

confidence: 99%

CD45RC Expression of Circulating CD8+ T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients

Lemerle

Garnier

Planchais

et al. 2019

JCM

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Predictive biomarkers of acute rejection (AR) are lacking. Pre-transplant expression of CD45RC on blood CD8+ T cells has been shown to predict AR in kidney transplant (KT) patients. The objective of the present study was to study CD45RC expression in a large cohort of KT recipients exposed to modern immunosuppressive regimens. CD45RC expression on T cells was analyzed in 128 KT patients, where 31 patients developed AR, of which 24 were found to be T-cell mediated (TCMR). Pre-transplant CD4+ and CD8+ CR45RChigh T cell proportions were significantly higher in patients with AR. The frequency of CD45RChigh T cells was significantly associated with age at transplantation but was not significantly different according to gender, history of transplantation, pre-transplant immunization, and de novo donor specific anti-Human Leucocyte Antigen (HLA) antibody. Survival-free AR was significantly better in patients with CD8+ CD45RChigh T cells below 58.4% (p = 0.0005), but not different according to CD4+ T cells (p = 0.073). According to multivariate analysis, CD8+ CD45RChigh T cells above 58.4% increased the risk of AR 4-fold (HR 3.96, p = 0.003). Thus, pre-transplant CD45RC expression on CD8+ T cells predicted AR, mainly TCMR, in KT patients under modern immunosuppressive therapies. We suggest that CD45RC expression should be evaluated in a prospective study to validate its usefulness to quantify the pre-transplant risk of AR.

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Pre-transplant CD45RC expression on blood T cells differentiates patients with cancer and rejection after kidney transplantation

Cited by 7 publications

References 29 publications

Transient antibody targeting of CD45RC inhibits the development of graft-versus-host disease

Transient antibody targeting of CD45RC inhibits the development of graft-versus-host disease

Role of novel biomarkers in kidney transplantation

CD45RC Expression of Circulating CD8+ T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients

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