Abstract
BackgroundGrowing evidence suggest that type 2 immune effectors play a role in solid organ transplantation. The aim of this study was to evaluate the impact of blood count eosinophils (BCEo) on immunological outcomes in kidney transplant recipients with stable graft function after 3 months post-transplant.MethodWe performed cause-specific Cox model considering BCEo, the use of calcineurin inhibitors and systemic corticoids as time-dependent explicative variables on a prospective cohort of 1013 kidney transplant patients who experienced kidney allograft rejection and/or the appearance of de novo donor specific antibodies after excluding common causes of increased BCEo..FindingsBCEo ≥ 0.3 G/L was associated with a 3-fold increased risk of rejection independent of immunosuppressive regimen after 3 months post-transplant in patients without pre-transplant DSAs and with CNI-based immunosuppression. No association between BCEo either with donor specific antibodies or graft survival was noticed.InterpretationThese observations in this large cohort support the hypothesis of eosinophils in allo-immunity in human and claim for further mechanistic research.FundingThis study was supported by the French National Research Agency, The “Institut de Recherche en Santé Respiratoire des Pays de la Loire” and the University hospital of Nantes.
Highlights
In clinical practice after eliminating common causes of an increase in blood count eosinophils (BCEo) (PTLD, acute allergic process, parasitic or viral infections, BCEo 0.3 G/L could lead to monitor more regularly biological parameters associated with rejection such as de novo donor-specific antibody (DSAdn) (IgG anti-human leukocyte antigen (HLA) class I or II with MFI > 2000) and/or proteinuria > 1 g/24 h and/or hematuria (> 10 red blood cells/mL) and/or an increase of 25% in serum creatinine compared to baseline
Multicentric studies challenging BCEo > 0.3 G/L threshold and evaluating the optimal time points of BCEo titration are needed. These observations open new perspectives and directions that raise the question of the involvement of eosinophils and type 2 immunity in kidney allograft rejection
Type 2 inflammation is mainly characterized by a high rate of IL-4, IL-5 and IL-13 secretion leading to IgE synthesis, an increase in blood count eosinophils (BCEo) and eosinophil and mast cell/basophil tissue infiltration
Summary
Type 2 inflammation is mainly characterized by a high rate of IL-4, IL-5 and IL-13 secretion leading to IgE synthesis, an increase in blood count eosinophils (BCEo) and eosinophil and mast cell/basophil tissue infiltration. IL-4 and IL-13 participate in allograft rejection via the upregulation of adhesion molecules such as VCAM1, which is mainly present on the eosinophil membrane [10], and the increase in eotaxin secretion by endothelial cells, which is crucial for eosinophil diapedesis in synergy with IL-5 [11,12]. These observations suggest that activated eosinophils infiltrating allografts can induce graft injuries and dysfunction in a type 2 inflammation dependent manner.
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