Project: HLA-DQ immunogenicity

Project name: HLA-DQ immunogenicity – focus on 2MM1DSA

Project leaders: Anat R. Tambur & Lloyd d’Orsogna

Detailed project description:

One of the limitations of studying HLA epitopes in the context of population studies is the heterogeneity of the cohort in terms of induction therapy, maintenance immunosuppression, medication compliance, other sensitizing events during the post-transplant course (like significant infections), etc. To minimize the effects of these factors we will focus on a subpopulation of patients who receive a donor with 2 mismatches at the DQ locus, developed de-novo DSA to one of the mismatched alleles, but did not develop DSA to the other mismatched allele.

In this project we will compare qualities of the “DSA allele” as it compared with the “non-DSA allele” and compare both to the recipient alleles. Analysis will include the use of HLA-Matchmaker, EMS-2D, EMS-3D, PIRCHE-II and individual amino-acids (AA). For the qualities of the AA differences we will use PyMol simulation as guidance. Selected samples will be studied also by absorption/elution experiments.

Milestones in years:

2020:   Data collection – analysis as data will be submitted

2021:   Continue data collection, continue analysis, identify samples for absorption/elution studies

2022:   Continue Absorption/elution studies, finalize analysis

Patient/sample description (if applicable, details, inclusion/exclusion criteria):

Subset of “Definition of Immunogenic Epitopes”. Laboratories will need to include information if serum samples are available for absorption/elution studies although absence of serum will not constitute an exclusion

Data, samples, additional assays required:

Subset of “Definition of Immunogenic Epitopes

Kidney transplant biopsy pathology findings: Not essential requirement

Kidney transplant biopsy is considered the “Gold Standard” pathology test for the diagnosis of antibody mediated rejection. As part of the study on immunogenicity of HLA-DQ mismatches it is requested that participants also submit kidney biopsy results to the IHIWS project team if and when possible. The kidney biopsy results will be correlated with the SAB assay results to determine the pathogenicity of detected HLA-DQ donor-specific antibodies. This information will be critical to determine the clinical relevance of HLA-DQ antibodies.

Submission of kidney biopsy findings is NOT an essential requirement for participation in the 18th IHIWS.

For centres that do wish to also submit the kidney transplant biopsy results linked to specific transplant pairs submitted to the IHIWS database, then biopsy results should be submitted according to the Banff criteria (0-3 score) for each lesion type, as per Transplantation 2018: 102; 1795 (Table 2). Results can be submitted using the attached excel spreadsheet.