Phenotype of HLA antibodies in patients with antibody mediated rejection
File(s)
Author(s)
Gueret-Wardle, Alexander
Type
Thesis
Abstract
Renal transplantation is the treatment of choice for patients with end stage kidney disease.
Not only is there a survival benefit but there is a significant improvement in quality of life
when compared to patients that remain on dialysis.
Although short term graft survival has improved in the last 60 years, late graft loss remains a
problem. Antibody mediated rejection (AMR) is a major determinant of kidney allograft
failure, with chronic AMR being the leading cause of late graft loss. Donor specific anti-HLA
antibodies (DSA) have been reported to be strongly associated with an increased risk of
rejection and allograft failure. Although the presence of anti-HLA DSAs is thought to be one
of the most important biomarkers in predicting allograft failure there is no consensus on their
pathogenicity and no standardised protocol on how to approach their clinical management.
Whilst most DSAs are of immunoglobulin (Ig) G isotype Anti-HLA DSAs can also exist in IgM,
IgE and IgA subtypes, although their roles are less well understood.
The value of phenotyping these antibodies has not been fully established. The principal aim
of this work is to determine whether more sophisticated assays help predict outcomes for
those most at risk of allograft rejection.
The underlying hypothesis of this work is that phenotyping of DSAs helps stratify the risk of
poor outcomes according to the phenotype of rejection. Patients were recruited from
Imperial College Renal and Transplant centre. The results are presented in several related
studies. 1. IgG anti-HLA donor specific antibody subclass phenotyping in chronic antibody
mediated rejection (cAMR)
2. C1q Binding anti-HLA donor specific antibodies in patients with cAMR
3. What is the role of IgM anti-HLA donor specific antibodies in renal transplantation
4. Anti-HLA IgE: good, bad or indifferent?
Not only is there a survival benefit but there is a significant improvement in quality of life
when compared to patients that remain on dialysis.
Although short term graft survival has improved in the last 60 years, late graft loss remains a
problem. Antibody mediated rejection (AMR) is a major determinant of kidney allograft
failure, with chronic AMR being the leading cause of late graft loss. Donor specific anti-HLA
antibodies (DSA) have been reported to be strongly associated with an increased risk of
rejection and allograft failure. Although the presence of anti-HLA DSAs is thought to be one
of the most important biomarkers in predicting allograft failure there is no consensus on their
pathogenicity and no standardised protocol on how to approach their clinical management.
Whilst most DSAs are of immunoglobulin (Ig) G isotype Anti-HLA DSAs can also exist in IgM,
IgE and IgA subtypes, although their roles are less well understood.
The value of phenotyping these antibodies has not been fully established. The principal aim
of this work is to determine whether more sophisticated assays help predict outcomes for
those most at risk of allograft rejection.
The underlying hypothesis of this work is that phenotyping of DSAs helps stratify the risk of
poor outcomes according to the phenotype of rejection. Patients were recruited from
Imperial College Renal and Transplant centre. The results are presented in several related
studies. 1. IgG anti-HLA donor specific antibody subclass phenotyping in chronic antibody
mediated rejection (cAMR)
2. C1q Binding anti-HLA donor specific antibodies in patients with cAMR
3. What is the role of IgM anti-HLA donor specific antibodies in renal transplantation
4. Anti-HLA IgE: good, bad or indifferent?
Version
Open Access
Date Issued
2019-06
Date Awarded
2020-05
Copyright Statement
Creative Commons Attribution NonCommercial Licence
Advisor
Willicombe, Michelle
Pusey, Charles
Sponsor
Imperial College London
Publisher Department
Department of Immunology and Inflammation
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Medicine (Research) MD (Res)