Project: Testing the clinical utility of commercial Non-HLA antibody kits

Project leader: Raymond Fernando

Detailed project description:

There is anecdotal evidence that non-HLA antibodies are involved in early rejection episodes after renal transplantation. The evidential data comes from small, single centre studies, pre-dominantly focussing on one or a restricted number of non-HLA targets. Both One Lambda and Immucor have developed non-HLA antibody kits on the Luminex platform containing a wide range of non-HLA antibody targets. Currently, the true clinical relevance of non-HLA antibodies identified using these kits are yet to be established and international collaboration is required to address this issue. The non-HLA targets that are important may also be subject to regional variation because of local population genetics and environmental factors.

For the 18^th International Workshop, the aim is to initiate a pilot study in the context of renal transplantation. We are especially looking for laboratories who have already identified patient cohorts and determined non-HLA antibodies with (at least) one of the two vendors.  However, we welcome any laboratories interested in participation in the study. Reagents from both vendors will be made available free of charge. This pilot study will lay the foundation for a more extensive study during the 19^thworkshop. Participation of laboratories from all over the world is sought to answer the questions below:

• What are the pre-transplant levels of non-HLA antibodies in serum of patients who received a renal organ and had an uneventful course for at least 3 months post -transplantation (control population)?
• What are the pre-transplant levels of non-HLA antibodies in the serum of patients who received a kidney allograft and had an episode of biopsy proven rejection within the first month after transplantation in the absence of HLA donor specific antibodies?
• Are the levels of non-HLA antibodies higher in patients who had an immunological aetiology to their renal disease?
• Do the non-HLA antibodies levels change increase in the samples taken at the time of biopsy?

These data will aid in defining cut-offs and/or reference values, identifying non-HLA antibodies that correlate with rejection and those that are not markers of rejection.

Milestones in years:

• 2021: Recruitment of laboratories to participate in the study
• 2021-2022 Testing of serum/plasma samples with both One Lambda and Immucor non-HLA antibody kits
• 2022 Collation of data and analysis by the IHIWS bioinformatics team
• 2022 Presentation of the data at the 18^th IHIWS meeting

Patient description:

Inclusion criteria

• HLA unsensitised adult patients, consistently negative results with Luminex screening/identification kits
• Patients who had received their first kidney transplant

Exclusion criteria

• HLA antibody positive patients at the time of transplant
• Re-transplant patients
• HLA antibodies at time of rejection

Data required:

Patient data

• Gender
• Age
• Ethnicity (optional)
• Disease aetiology
• Presence of an episode of biopsy proven rejection within one moth post-transplantation
• Absence of rejection within 3 months after transplantation (control population)
• Serum/plasma creatine at 6 months post-transplant (optional)

Samples required:

• Serum sample used in the pre-transplant crossmatch or one ≤ 90 days pre-transplant if virtual crossmatch performed
• A serum sample stored on the day of the biopsy or close to the date of the rejection episode (optional)
• A serum sample from control patients 1 month post-transplant (optional)

Reagents/additional assays required:

Reagents used for running assays on the Luminex platform

Data infrastructure required:

xPONENT® software and Microsoft Excel