Understanding HLA-DQ in renal transplantation: a mini-review

Area of Science:

• Transplantation immunology
• Immunogenetics

Background:

• Human leukocyte antigen (HLA) mismatching, especially HLA-DQ, is a major driver of donor-specific antibodies (DSA) and adverse transplant outcomes.
• Traditional HLA typing methods often misclassify mismatches, hindering accurate immunogenicity assessment and clinical risk stratification.

Purpose of the Study:

• To highlight the critical role of advanced high-resolution HLA typing in improving the assessment of HLA-DQ mismatches.
• To discuss the limitations of current typing methods and the potential of emerging molecular mismatch algorithms.

Main Methods:

• Review of current literature on HLA mismatching, immunogenicity, and typing technologies.
• Analysis of the impact of amino acid differences, evolutionary divergence, and HLA-DQ expression complexities on T-cell alloreactivity and DSA development.

Main Results:

• High-resolution HLA typing offers superior mismatch assessment compared to traditional methods.
• Molecular mismatch algorithms and analysis of evolutionary factors show promise but require further validation for predicting individual patient outcomes.
• HLA-DQ expression variability, including heterodimer formation and alternative splicing, complicates risk evaluation.

Conclusions:

• Advanced high-resolution HLA typing is essential for refining graft selection, DSA monitoring, and personalized therapy in transplantation.
• Further research into the precise mechanisms of HLA-DQ immunogenicity is needed to advance transplantation science and improve patient outcomes.