Key Takeaways

• Allele specific anti-HLA reactivity was shown to occur in around 15% of patients awaiting transplantation.
• The use of extended HLA antibody detection panels may be most informative in sensitized patients.
• The study highlights the importance of assessing donor-recipient compatibility at the allele specific level.
• Allele-level donor and recipient genotyping is required for an optimal assessment of immunologic compatibility.

Summary Statement

Zavyalova et al. performed a comprehensive retrospective analysis of two years of HLA antibody testing data to define the prevalence and clinical impact of HLA allele-specific antibodies. The importance of defining HLA-specific antibodies at the allele-level when defining donor-recipient histocompatibility is clearly demonstrated.

Summary

Traditionally, the detection and characterization of HLA-specific antibodies identified reactivity towards well-defined serologic antigen groups. However, since the advent of single antigen bead technology, it has become well established that limiting the analysis to these serologic groups is insufficient since the epitope specific nature of HLA antibody frequently leads to the observation of reactivity patterns that map to positivity against selected alleles of a particular serologic antigen. This is an observation broadly referred to as allele-specific anti-HLA antibody reactivity.

This study from Zavyalova et al. looks at the frequency of allele-specific antibodies in a comprehensive patient cohort, examining 4,547 samples from 1,939 patients listed for heart, lung, and kidney transplantation. From this cohort, the authors showed that allele-specific antibodies were detected in 15.5% of samples or 25.2% of samples that showed anti-HLA positivity.

Furthermore, the authors were able to show that where the allele-specific antibody was predicted to be DSA, the cellular crossmatch result was 100% concordant, with 54/54 positive crossmatches identified. Retrospective analysis data also demonstrated that HLA allele-specific antibodies were informative in 2.9% of living donor and 4.7% of deceased donor crossmatches. These observations further support the notion that the allele-level evaluation of HLA-specific antibodies is crucial for the accurate assessment of donor-recipient immunologic compatibility.

The authors also highlight the importance of allele-level HLA typing resolution in both donors and recipients. The currently common practice of using low-resolution HLA genotyping methods often hinders the accurate assessment of histocompatibility.

An additional analysis was also performed across 45 samples from 45 patients to evaluate the use of extended antibody detection panels for the impact on allele-specific HLA antibody detection. This investigation showed a high degree of allele-specific reactivity with 61.4% and 31.8% of samples showing allele-specific reactivity for HLA class I and class II respectively. Here the authors have demonstrated that HLA allele-specific antibodies with reactivity outside of the standard SAB panels are not uncommon and that screening with reagents beyond the standard SAB may be necessary for sensitized patients.