Project name: Definition of non-immunogenic epitopes

Project leaders: Sebastiaan Heidt & Eric Spierings

Detailed project description:

Highly sensitized patients make antibodies against epitopes present on many HLA antigens. However, from the Eurotransplant Acceptable Mismatch program, we know that most highly sensitized patients have ‘holes’ in their immunological repertoire, such that acceptable mismatches can be defined. The aim of this study is to determine for a large number of highly sensitized patients to which epitopes no antibodies have been formed. By collecting such data, we can make an inventory of non-immunogenic or acceptable HLA epitopes.

To this aim, we will collect second-field molecular HLA typing and Luminex single antigen bead raw data from highly sensitized patients awaiting a renal transplant.

Milestones in years:

• 2020: Creation of a uniform way to enter second-field HLA typing data and Luminex SAB data, irrespective of vendor. Inclusion of as many laboratories worldwide as possible. Start of data collection
• 2021: Continuation of data collection and interim analyses
• 2022: Finalizing analyses

Patient description:

Highly sensitized patients (defined as a cPRA/cRF of >95%) awaiting a renal transplant.

Data required:

• Second-field molecular HLA typing for HLA-A, -B, -C, -DRB1, -DRB3-5, -DQB1, -DQA1, -DPB1, and -DPA1 of patient
• Luminex SAB raw data file, including lot number
• Prevention of prozone effect (specify method)

Samples required:

If no molecular typing at second field level is available for the patient, DNA would be required for the typing to be performed. In case no Luminex SAB data is present, a serum sample from the appropriate time-point is required.

Reagents/additional assays required:

For a proportion of laboratories, we expect to require additional second-field molecular HLA typing, as well as Luminex SAB analysis.

Data infrastructure required:

A uniform way to enter second-field HLA typing data and Luminex SAB data, irrespective of vendor.