HLA-B Leader Dimorphism Predicts BK Polyomavirus Replication After Kidney Transplant

Area of Science:

• Immunogenetics
• Transplantation immunology
• Virology

Background:

• BK polyomavirus (BKPyV) and Cytomegalovirus (CMV) commonly replicate post-kidney transplant, complicating management.
• Current strategies involve reducing immunosuppression, which risks graft rejection.
• Genetic factors like HLA evolutionary divergence (HED) and HLA-B leader dimorphism may influence antiviral responses.

Purpose of the Study:

• To compare HED and HLA-B leader dimorphism between kidney transplant recipients with and without viral replication in the first year.
• To investigate the potential of these genetic markers as predictors of BKPyV and CMV replication.

Main Methods:

• Analysis of 306 kidney transplants performed between 2019-2023.
• HLA typing of recipients and donors to determine HED and HLA-B leader dimorphism.
• Multivariate analysis to assess associations with viral replication (BKPyV nephropathy and CMV infection).

Main Results:

• BKPyV replication occurred in 22.5% and CMV infection in 40.2% of recipients within the first year.
• Donor-recipient HLA-B leader mismatch demonstrated a protective effect against BKPyV replication (OR=0.48, p=0.02).
• No significant association was found between HLA-B leader dimorphism and CMV replication (OR=1.42, p=0.169).

Conclusions:

• Donor-recipient HLA-B leader dimorphism may serve as a predictive marker for BKPyV replication risk in kidney transplant recipients.
• Further validation in independent cohorts is necessary to confirm these findings.
• HLA-B leader dimorphism appears to influence BKPyV, but not CMV, post-transplant outcomes.