HLA-A, C, B, DRB1, DQB1 Haplotypes identified among hematopoietic stem cell transplant patients.
Anajane G. Smith, Maggie Sprague, Randy Williams, Caren Brinkema, Kelly O’Connor, Sue McKinney, Lois Regen, John A. Hansen. Clinical Immunogenetics Laboratory, Fred Hutchinson Cancer Research Center, Seattle, WA.

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Previous studies have demonstrated that HLA-A, C, B, DRB1 and DQB1 allele matching optimizes outcome in unrelated donor hematopoietic cell transplantation (HCT). The current analysis includes 95 HCT recipients who had sufficient family members available for definitive assignment of haplotypes. All cases were tested using DNA methods for analysis of the HLA-A, C, B, DRB1 and DQB1 loci. 74 patients were prospectively sequenced at HLA-A and B (exons 2, 3, 4) and HLA-DRB1 (exon 2) and another 21 patients were sequenced to confirm certain unusual HLA-A and B alleles or haplotypes. HLA-C typing was performed using intermediate resolution sequence specific primers. DQB1 alleles were identified by reverse probe hybridization. Among the 74 prospectively typed patients, 21 HLA-A alleles and 34 HLA-B alleles were identified. The B*35 family was most diverse with 4 alleles identified: B*3501 (n=8), 3502 (n=2), 3503 (n=5) and 3508 (n=1). 122 unique HLA-A, C, B, DRB1, DQB1 haplotypes were identified in the 74 patients, however, only 11 haplotypes were detected 2 or more times:
 

 
Among the 21 other patients, haplotypes associated with A*2603, 3004, 0305, B*0709, 0809, 1508, 1509, 1804, 2712, 4405, 5002, 5107, 5110 and 7301 were identified. A novel A*26 allele with a single nucleotide substitution of G instead of C at position 180, exon 2, was encoded by a patient and his father on the haplotype A*26new, C*12CF, B*3801, DRB1*1104, DQB1*0301. These results further illustrate the extraordinary diversity of HLA alleles and haplotypes and the need for sensitive, high resolution DNA typing methods in laboratories responsible for optimizing HLA matching for hematopoietic stem cell transplantation.