A descriptive analysis of non-human leukocyte antigens present in renal transplant donor-recipient pairs.

Introduction: End stage renal disease (ESRD) is the irreversible deterioration of renal function requiring renal replacement therapy by dialysis or transplant. Human leucocyte antigens (HLA) have been well examined however research still is required into the non-HLA antibodies. Antibody mediated rejection (AMR) can be seen in the absence of HLA antibodies on biopsies of patients who have received identical transplants; anti-endothelial cell antibodies may explain this. Investigation into endothelial cell antigens on donor and recipient endothelium may elucidate and stratify the degree of risk of any given transplant and may guide towards the best matched donor.

Methods: Protein array analysis was carried out on 8 patient pairs using nitro-cellulose membranes and biotinylated detection antibodies. The fluorescence emitted was captured by X-Ray film and results were recorded with ImageJ software. A fold increase of more than 2 was considered to be positive.

Results: 11 proteins identified had a fold increase of increase ≥2 and were present in ≥2 patient pairs which may point to potential clinical utility. Nectin2/CD112 may be measured in order analyse graft survival time in transplant recipients. Prognosticating renal failure has clinical importance and potential markers that have been identified to aid which include MEPE, CRELD2, and TIMP-4. Novel pharmacological therapies for specific biomarkers identified in this study include JAM-A, E-Selectin, CD147, Galectin-3, JAM-C, PAR-1, and TNFR2.

Conclusion: Protein analysis showed differences in expression of antigens between patients with and without Chronic Kidney Disease (CKD). This information could be used at the matching stage of renal transplantation and also in the treatment of rejection episodes. The results highlight biomarkers that potentially prognosticate and pharmacological therapies that may ameliorate kidney disease and rejection in ESRD and transplant recipients.