Project name: The clinical relevance of non-HLA antibodies in Kidney, Lung and Heart transplantation
Project leaders: dr. Henny G. Otten and prof. dr. Elain Reed
Detailed project description:
Non-HLA antigens as targets in organ transplantation
In recent years multiple studies have been published showing a relation between the presence of non-HLA antibodies and graft loss and/or rejection episodes. These antibodies recognize multiple antigens which are mostly expressed within the cell, whereas their tissue expression is not restricted to the transplanted organs. Although none of these studies have proven that autoantibodies directly contribute to the pathogenesis of graft dysfunction, the data indicate that detection of non-HLA antibodies may be useful in identifying patients at risk for graft loss. The reason for non-HLA antibody formation is not yet known and appears unlike the classical sensitizing events stimulating HLA antibody formation. Non-HLA antibodies can be detected using reagents from different companies and also with tests manufactured in-house. This leads to technical variation which may be a reason why at present there is no standard assay defining the impact of non-HLA antibodies on graft loss. In addition, the definition of a positive result is usually not based on a clinically relevant definition. During the 18th IHIWS, in kidney, lung and heart transplantation, we aim to 1) Define the clinical relevance of non-HLA antibodies present prior to transplantation and during rejection episodes in a multi-center study. This will be defined in the absence of donor-specific HLA antibodies. 2) Provide insight on the technical differences between non-HLA assays used and relate these to their clinical relevance, and 3) To use standardized reference reagents for the testing of non‐HLA Abs. These studies can form a basis for a larger, more comprehensive study during the 19th IHIWS.
Milestones in years:
For this study only sera are included from patients without pretransplant DSA as defined by luminex: less than 500MFI net values when background MFI values are subtracted. Patients included require a matched patient with comparable recipient age, recipient gender, donor age, donor gender, donor type, mean cold ischemia time, and immunosuppression regime.
Group 1: Pretransplant sera from kidney-, lung-, or heart transplant patients who suffered from one or more rejection episode(s) within the first year after transplantation in the absence of DSA. Data from histopathological analysis should be available from biopsies taken during rejection, in order define humoral rejection according to BANFF 2018 criteria.
Group 2: The matched patient cohort included should not have developed rejection within the first year after transplantation. When data from protocol biopsies are available then these will be included in analysis.
Data required (number, type of data, inclusion/exclusion criteria):
Non-HLA luminex data from at least 140-150 patients with and the same number of matched controls (preferentially much more pairs) without rejection, all in the absence of DSA. The inclusion/exclusion criteria are listed in the Patient/sample description. Example power analysis for 140 matched patient pairs:
From each patient one pretransplant serum sample is required and one taken at the time of rejection. Each time point would yield a total of at least 280 samples (patients + matched controls) which will be tested using commercial non-HLA Luminex tests from both Immucor and One Lambda. Participating centers can send the sera to the UMC Utrecht for testing which rules out inter-laboratory variability. Luminex results in combination with clinical data will be analysed centrally and discussed with all participants of the study. A standard list with required clinical data will be send to each participating center. The above information will be updated in January.
Reagents/additional assays required:
Commercial non-HLA Luminex tests from Immucor and Thermo Fischer One Lambda.
Data infrastructure required:
Database from the 18th IHIWS.