Anti-Angiotensin II Type 1 Receptor Antibodies and Kidney Transplant Outcomes

Summary

Incompatibility between non-genetically identical donors and recipients has been increasingly recognized as the main contributing factor to solid allograft rejection and failure, through the triggering of donor-specific responses mediated by T- and B-lymphocytes. The Human Leucocyte Antigen (HLA) system has been identified as the main target of donor-specific responses, especially through the production by the recipient of antibodies directed toward non-self donor HLA molecules expressed on the allograft endothelium. As a consequence, in organ transplantation, the current approach to immunological risk stratification, patient monitoring and rejection diagnosis is based on biomarkers derived from the HLA system. However, this approach does not provide a sufficient accuracy for the risk stratification and the diagnosis of immunological complications in solid organ transplantation, which still remain the dominant cause of allograft failure.

A recent body of evidence supports that specific non-HLA antigens expressed on the allograft endothelium may be relevant to allograft rejection, suggesting that a new strategy to transplant diagnostic testing at a non-HLA level would help to overcome the limitations of the current HLA-based approach to immunological assessment of transplant recipients. Among antibodies to non-HLA endothelial antigens, angiotensin II type 1 receptor activating antibodies have been the most widely reported antibodies to associate with the occurrence of allograft rejection, dysfunction and loss, even if their independent role, with respect to the presence of concomitant anti-HLA antibodies, has not been demonstrated.

Conditions

• Kidney Transplant Failure and Rejection

Interventions

DIAGNOSTIC_TEST

Anti-angiotensin II type 1 receptor antibody measurement

Anti-angiotensin II type 1 receptor antibodies are assessed using quantitative ELISA in stored serum samples obtained within the first year after transplantation

DIAGNOSTIC_TEST

Measurement of ENDAT expression level allograft

Endothelial-associated transcript expression level is assessed using microarray in stored kidney allograft biopsies obtained within the first year after transplantation

OTHER

Allograft survival

OTHER

Allograft rejection appearance

Sponsors & Collaborators

• Center for Cardiovascular Research Berlin

  collaborator OTHER

• Paris Translational Research Center for Organ Transplantation

  lead OTHER

Principal Investigators

• Carmen Lefaucheur · Paris Translational Research Center for Organ Transplantation

• Alexandre Loupy · Paris Translational Research Center for Organ Transplantation

• Duska Dragun · Clinic for Nephrology and Critical Care Medicine, Campus Virchow-Klinikum and Center for Cardiovascular Research, Medical Faculty of the Charité Berlin

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-01-01

Primary Completion

2017-12-31

Completion

2017-12-31

Countries

• France

Study Locations