Frequency of Class I common or well documented null alleles in National Marrow Donor Program high resolution typing programs

Abstract

Aim NMDP high resolution (HR) testing programs require typing for common or well documented (CWD) null alleles in alignment with Mack et al., Tissue Antigens. 2013: 81(4): 194–203 (CWD 2.0). The aim of this study was to determine the frequency of CWD 2.0 Class I null alleles in NMDP HR typing programs and whether these alleles occur outside of their expected haplotypes. Methods Labs performing HR typing routinely test exons 2–4, then additional regions depending on where a CWD null allele polymorphism is located. Typing methods include SSO, SBT, and NGS. HR Class I typing results from historic adult donor registry samples and CBU samples performed in 2013–2015 were queried for reports of CWD null alleles. Results Four different Class I CWD null alleles were reported a total of 35 times in 41,864 tests. B∗51:11N is expected in the A∗02∼DRB1∗04 haplotype but was observed in A∗03:01∼C∗07:02∼DRB1∗04:02. C∗04:09N was observed with its most common haplotype A∗23:01∼B∗44:03∼DRB1∗07:01 in 53% of cases and with B∗44 in 100% of cases. The common A∗02:53N was not reported; it occurs in up to 0.10% of Chinese populations. The remainder of the CWD nulls were not observed. G group frequency is the null allele frequency within the two digit G group typing. Conclusion Although the frequency of Class I CWD null alleles in the queried HLA results is low, they may warrant continued routine typing. Failure to identify a null allele results in a hidden mismatch between donor and patient. However, lab costs increase due to the additional typing required to detect polymorphisms located outside of exons 2–3. As exon 7 is not routinely tested, typing for C∗04:09N only in the presence of B∗44 may be a future consideration for NMDP HR contracts and policies. Download : Download full-size image