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NEW HLA CLASS I ALLELES AND NULL ALLELES EFFECT UNRELATED BONE MARROW DONOR SEARCHES: DO WE STILL NEED SEROLOGIC TYPING?
Douglas M. Smith, MD, PhD, Judith E. Baker, BS, William B. Gardner, BS and Edward D. Agura, MD. Dallas TX, USA, Balyor University Medical Center, 75246, Pathology and Dallas TX, USA, Baylor University Medical Center, 75246, Bone Marrow Transplant Center.

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This report describes seven cases where we found either discrepancies between the serologic HLA typing results and those found with PCR-ssp or we found a new HLA class I allele. Six of these cases were found in the course of 269 searches for unrelated bone marrow donors, involving 1,428 HLA class I typings, including 502 DNA sequence based typings (SBT). Two discrepancies were caused by null alleles, including A*2409N and a new A*02 null allele. One new B*40 allele typed serologically as B41 and one new B*07 allele typed serologically as B42. The new A*02 null alleles was interesting because it typed as A*0201 even when using a high resolution PCR-ssp kit (One Lambda). The null allele resulted from a single base pair substitution in codon 164, which creates a premature stop codon and disrupts a critical disulphide bond. This substitution matches a similar substitution in the 2308N allele. SBT was able to detect each of these new or rare alleles, however, in our institution SBT is usually performed as the last step in matching the patient and donor, therefore the disrepancies between serologic and PCR-ssp typing allowed us to identify these new or rare alleles early in the donor search. It should also be kept in mind that many mutations that cause null alleles occur outside the area normally DNA sequenced.
Conclusions: New alleles and null alleles are not extremely rare. They affected 6 of 269 unrelated donor searches at our institution. Serologic typing was important in detecting 4 of these cases early in the search process. SBT may detect important alleles that cannot be detected even by high resolution PCR-ssp.