Time-dependent blood eosinophilia count increases the risk of kidney allograft rejection

Colas, Luc; Bui, Linh; Kerleau, Clarisse; Lemdani, Mohamed; Autain-Renaudin, K.; Magnan, A.; Giral, Magali; Brouard, Sophie

doi:10.1016/j.ebiom.2021.103645

Cited by 7 publications

(5 citation statements)

References 62 publications

(71 reference statements)

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“…A recent cross-sectional study investigating kidney recipients diagnosed with ABMR found circulating anti-HLA IgE (with the same specificities as IgG) and identified in the graft deposits of IgE and the presence of mast cells and activated basophils ( 28 ). Moreover, another recent paper revealed that elevated eosinophil counts were associated with an increased risk of subsequent rejection and a trend to a higher incidence of de novo (IgG) DSA ( 44 ). While IgE was not analyzed, eosinophils are another hallmark of type 2 inflammation, thus these data also indirectly point to a role for Th2-driven immunity, including IgE in alloreactivity.…”

Section: Discussionmentioning

confidence: 99%

Prospective assessment of pre-existing and de novo anti-HLA IgE in kidney, liver, lung and heart transplantation

Mucha,

Cho,

Weijler

et al. 2023

Front. Immunol.

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IntroductionAntibody mediated rejection (ABMR) is a major factor limiting outcome after organ transplantation. Anti-HLA donor-specific antibodies (DSA) of the IgG isotype are mainly responsible for ABMR. Recently DSA of the IgE isotype were demonstrated in murine models as well as in a small cohort of sensitized transplant recipients. In the present study, we aimed to determine the frequency of pre-existing and de novo anti-HLA IgE antibodies in a cohort of 105 solid organ transplant recipients.MethodsWe prospectively measured anti-HLA IgE antibodies in a cohort of kidney (n=60), liver, heart and lung (n=15 each) transplant recipients before and within one-year after transplantation, employing a single-antigen bead assay for HLA class I and class II antigens. Functional activity of anti-HLA IgE antibodies was assessed by an in vitro mediator release assay. Antibodies of the IgG1-4 subclasses and Th1 and Th2 cytokines were measured in anti-HLA IgE positive patients.ResultsPre-existing anti-HLA IgE antibodies were detected in 10% of renal recipients (including 3.3% IgE-DSA) and in 4.4% of non-renal solid organ transplant recipients (heart, liver and lung cohort). Anti-HLA IgE occurred only in patients that were positive for anti-HLA IgG, and most IgE positive patients had had a previous transplant. Only a small fraction of patients developed de novo anti-HLA IgE antibodies (1.7% of kidney recipients and 4.4% of non-renal recipients), whereas no de novo IgE-DSA was detected. IgG subclass antibodies showed a distinct pattern in patients who were positive for anti-HLA IgE. Moreover, patients with anti-HLA IgE showed elevated Th2 and also Th1 cytokine levels. Serum from IgE positive recipients led to degranulation of basophils in vitro, demonstrating functionality of anti-HLA IgE.DiscussionThese data demonstrate that anti-HLA IgE antibodies occur at low frequency in kidney, liver, heart and lung transplant recipients. Anti-HLA IgE development is associated with sensitization at the IgG level, in particular through previous transplants and distinct IgG subclasses. Taken together, HLA specific IgE sensitization is a new phenomenon in solid organ transplant recipients whose potential relevance for allograft injury requires further investigation.

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Section: Discussionmentioning

confidence: 99%

Prospective assessment of pre-existing and de novo anti-HLA IgE in kidney, liver, lung and heart transplantation

Mucha,

Cho,

Weijler

et al. 2023

Front. Immunol.

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“…CCL11 may also attract T cells and macrophages in addition to eosinophils and enable the recruitment of more inflammatory cells into the graft. Altogether, a triple connexion would be easily postulated between CCL11, CCR3 and eosinophils with allograft rejection [55] [56]. However, in human heart transplants, CCR3 expression was studied in endomyocardial biopsies and it was found to be most intense at sites of focal T cell infiltrates and was associated non-significantly with acute rejection [28], while CCR3 mRNA was described as absent in acute rejection biopsies in human renal transplants [20].…”

Section: Discussionmentioning

confidence: 99%

Chemokine Receptors CCR1, CCR3, CCR7 and Chemokines CX3CL1 and CCL5 are Significantly Up-Regulated and Very Reliable for Acute Rejection Diagnosis of Kidney Transplants

Dias-Pinto¹,

Oliveira²

2023

OJNeph

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Background: The allo-immune response following organ transplantation constitutes one of the main determinants concerning both short-and longterm outcomes in renal graft recipients. Chemokines and their receptors play a diversified and important role, either homeostatic or inflammatory and direct different immune-competent cell types to the allograft. While deeply studied in the last two decades, controversy persists as a result of chemokines' pleiotropic actions. We report our analysis of CCR1, CCR3, CCR7, CCL5 and CX3CL1 expression or synthesis by graft-infiltrating cells in human kidney transplants (KTx). At the same time, we tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies (Fnab) were performed either on days 7 or 14 post-transplantation among stable KTx and on the day of acute rejection (AR) diagnosis. Fnab cytopreparations were studied by the enzymatic avidin-biotin complex staining for CCR1, CCR3, CCR7 and CX3CL1. From another subgroup of cases, Fnab samples were cultured for 48 hours and the supernatants were analysed for CCL5 by ELISA. Results: The group of AR cases showed a significantly up-regulated expression of CCR1, CCR3, CCR7 and CX3CL1 and a significantly higher synthesis of CCL5. The positive predictive values were respectively 92%, 97%, 85%, 76% and 78% and negative predictive values were by the same order, 100%, 73%, 100%, 98% and 83%. Conclusions: Our study permits us to advance that CCR1 and CCR3 play a significant and non-redundant role in acute rejection, and it is the first report of CCR3 association with rejection, probably related to CCL5. The presence inside the graft of significant up-regulation for CCR7 surmises that part of antigen presentation may be performed there without being re-How to cite this paper: Dias-Pinto, P.X. and Oliveira, J.G.G. (2023) Chemokine Receptors CCR1, CCR3, CCR7 and Chemokines CX3CL1 and CCL5 are Significantly Up-Regulated and Very Reliable for

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“…In addition eosinophils express CD154 and the number of eosinophils in circulation are a biomarker of solid organ transplant rejection ( 44 , 103 ). Activated Basophils express CD154, IL4 and IL13 and induce B cell expression of IgE ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

The Inhibition of CD40/CD154 Costimulatory Signaling in the Prevention of Renal Transplant Rejection in Nonhuman Primates: A Systematic Review and Meta Analysis

Perrin¹,

Magill²

2022

Front. Immunol.

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The prevention of allograft transplant rejection by inhibition of the CD40/CD40L costimulatory pathway has been described in several species. We searched pubmed for studies reporting the prevention of kidney transplant rejection in nonhuman primates utilizing either anti CD40 or anti CD40L (CD154) treatment. Inclusion of data required treatment with anti CD40 or anti CD154 as monotherapy treatment arms, full text available, studies conducted in nonhuman primate species, the transplant was renal transplantation, sufficient duration of treatment to assess long term rejection, and the reporting of individual graft survival or survival duration. Eleven publications were included in the study. Rejection free survival was calculated using the Kaplan-Meier (KM) life test methods to estimate the survival functions. The 95% CI for the medians was also calculated. A log-rank test was used to test the equality of the survival curves between control and treatment arms (CD40 and CD154). The hazard ratio for CD154 compared to CD40 and 95% CI was calculated using a Cox proportional-hazards model including treatment as the covariate to assess the magnitude of the treatment effect. Both anti CD40 and anti CD154 treatments prevented acute and long term graft rejection. The median (95% CI) rejection free survival was 131 days (84,169 days) in the anti CD40 treated animals and 352 days (173,710 days) in the anti CD154 treated animals. Median survival in the untreated animals was 6 days. The inhibition of transplant rejection was more durable in the anti CD154 group compared to the anti CD40 group after cessation of treatment. The median (95% CI) rejection free survival after cessation of treatment was 60 days (21,80 days) in the anti CD40 treated animals and 230 days (84,552 days) in the anti CD154 treated animals.

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Time-dependent blood eosinophilia count increases the risk of kidney allograft rejection

Cited by 7 publications

References 62 publications

Prospective assessment of pre-existing and de novo anti-HLA IgE in kidney, liver, lung and heart transplantation

Prospective assessment of pre-existing and de novo anti-HLA IgE in kidney, liver, lung and heart transplantation

Chemokine Receptors CCR1, CCR3, CCR7 and Chemokines CX3CL1 and CCL5 are Significantly Up-Regulated and Very Reliable for Acute Rejection Diagnosis of Kidney Transplants

The Inhibition of CD40/CD154 Costimulatory Signaling in the Prevention of Renal Transplant Rejection in Nonhuman Primates: A Systematic Review and Meta Analysis

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