establishment-analysis-acute-antibody-mediated-rejection-murine

Establishment and Analysis of Acute Antibody-Mediated Rejection in Murine Cardiac Transplantation

A major contributor to allograft failure in cardiac transplant recipients is antibody-mediated rejection (AMR). The mouse AMR model, therefore, serves as ...

The Third Affiliated Hospital of Sun Yat-sen University

Chronic rejection is the primary cause of late allograft failure, however, the current treatments for chronic rejection have not yielded desirable therapeutic effects. B cell activation and donor-specific antibody (DSA) production are the primary factors leading to chronic rejection. Bruton's tyrosine kinase (BTK) plays a key role in the activation and differentiation of B cells and in antibody production. This study investigated the efficacy of blocking BTK signalling in the prevention of chronic rejection. BTK signalling was blocked using the BTK inhibitor ibrutinib and gene knockout. In vitro assays were conducted to examine the consequences and underlying mechanisms of BTK blockade in regards to B cell activation, differentiation, and antibody secretion. Additionally, we established a cardiac transplantation mouse model of chronic rejection to explore the preventive effects and mechanisms of BTK ablation on chronic rejection. Ablating BTK signalling in vitro resulted in the inhibition of B cell activation, differentiation, and antibody production. In vivo experiments provided evidence that ablating BTK signalling alleviated chronic rejection, leading to reduced damage in myocardial tissue, neointimal hyperplasia, interstitial fibrosis, inflammatory cell infiltration, and C4d deposition. Allograft survival was prolonged, and B cell responses and DSA production were inhibited as a result. We confirmed that ablation of BTK signalling inhibited B cell response by blocking downstream PLCγ2 phosphorylation and inhibiting the NF-κB, NFAT, and ERK pathways. Our findings demonstrated that ablation of BTK signalling inhibited B cell activation and differentiation, reduced DSA production, and effectively prevented chronic rejection.

Bruton's tyrosine kinase ablation inhibits B cell responses and antibody production for the prevention of chronic rejection in cardiac transplantation.

Delayed graft function (DGF) shortens the survival time of transplanted kidneys and increases the risk of rejection. Current methods are inadequate in predicting DGF. More precise tools are required to assess kidney suitability for transplantation. Cold-inducible RNA-binding protein (CIRBP) expression has been linked to acute kidney injury, suggesting its potential as a new biomarker for transplanted kidney function.

Assessing donor kidney function: the role of CIRBP in predicting delayed graft function post-transplant.

Expanded criteria donors (ECD) have the potential to greatly increase the donor organ pool but pose a higher risk of delayed graft function (DGF) post-transplantation. Uridine diphosphate-glucose (UDP-Glc) plays a significant role in extracellular signaling related to tissue damage and retains stability for detection. Donor urinary UDP-Glc level may be an appropriate and effective biomarker for predicting DGF.

Article	Year
Bruton's tyrosine kinase ablation inhibits B cell responses and antibody production for the prevention of chronic rejection in cardiac transplantation. Clinical immunology (Orlando, Fla.)\| PubMed ID: 38365047	2024
Assessing donor kidney function: the role of CIRBP in predicting delayed graft function post-transplant. Frontiers in immunology\| PubMed ID: 39896811	2024
Preoperative donor urinary UDP-Glc as an independent risk factor for delayed graft function. Frontiers in immunology\| PubMed ID: 40165952	2025

Qianghua Leng

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