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

Acute antibody-mediated rejection (AAMR) is an important cause of cardiac allograft dysfunction, and more effective strategies need to be explored to improve allograft prognosis. Interleukin (IL)-6/IL-6R signaling plays a key role in the activation of immune cells including B cells, T cells and macrophages, which participate in the progression of AAMR. In this study, we investigated the effect of IL-6/IL-6R signaling blockade on the prevention of AAMR in a mouse model. We established a mouse model of AAMR for cardiac transplantation  presensitization of skin grafts and addition of cyclosporin A, and sequentially analyzed its features. Tocilizumab, anti-IL-6R antibody, and recipient IL-6 knockout were used to block IL-6/IL-6R signaling. We demonstrated that blockade of IL-6/IL-6R signaling significantly attenuated allograft injury and improved survival. Further mechanistic research revealed that signaling blockade decreased B cells in circulation, spleens, and allografts, thus inhibiting donor-specific antibody production and complement activation. Moreover, macrophage, T cell, and pro-inflammatory cytokine infiltration in allografts was also reduced. Collectively, we provided a highly practical mouse model of AAMR and demonstrated that blockade of IL-6/IL-6R signaling markedly alleviated AAMR, which is expected to provide a superior option for the treatment of AAMR in clinic.

Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model.

[This corrects the article DOI: 10.3389/fimmu.2021.778359.].

Corrigendum: Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model.

Delayed graft function (DGF) is a type of acute renal failure that is closely linked to the immune system. The objective of this study is to investigate immune trends during the perioperative period of renal transplantation and compare the variations between patients with DGF and immediate graft function (IGF). A total of 48 kidney transplant patients were enrolled. Parameters including stimulated adenosine triphosphatase concentrations (sATP), nonstimulated ATP concentrations, white blood cells, and lymphocyte count were assessed. Patients were categorized into the DGF or IGF group. Clinical information and changes in immune markers were compared. Receiver operating characteristic analysis was performed to determine the sensitivity and specificity in predicting DGF. Additionally, separate immune function analyses were conducted for the 3 infection cases. Following induction immunosuppressive therapy, white blood cells, and neutrophil count showed a significant initial increase followed by a gradual decline. Lymphocyte count, nonstimulated ATP concentrations, and sATP exhibited an initial significant decrease followed by a slow recovery. Immune markers between the DGF and IGF groups were significantly different at day 4 after renal transplantation. Only sATP levels at day 4 after renal transplantation (area under the curve = 0.731, sensitivity = 0.864, specificity = 0.684) demonstrated predictive value for DGF occurrence. Among the 3 infection cases, 2 cases exhibited persistently decreased sATP levels and died within the first month and 6 months, while the remaining case showed a recovery of sATP levels at D9 and survived. These findings indicate that sATP level can potentially serve as a biomarker reflecting the impact of immunosuppressants. Poor recovery of sATP may be associated with DGF, infection, or even mortality.

Prospective study on immune function in renal transplant patients during perioperative period: A prospective cohort study.

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
Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model. Frontiers in immunology\| PubMed ID: 34777394	2021
Corrigendum: Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model. Frontiers in immunology\| PubMed ID: 34868092	2021
Prospective study on immune function in renal transplant patients during perioperative period: A prospective cohort study. Medicine\| PubMed ID: 39432644	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

Maolin Ma

Biography

JoVE Journal Publications

Other Publications