HLA–B*35 ALLELE FREQUENCIES AND HAPLOTYPE LINKAGE AMONG 500 HEMATOPOIETIC STEM CELL TRANPLANT PATIENTS, IMPLICATIONS FOR MATCHING WITH UNRELATED DONORS

1.1
TITLE: HLA–B*35 ALLELE FREQUENCIES AND HAPLOTYPE LINKAGE AMONG 500 HEMATOPOIETIC STEM CELL TRANPLANT PATIENTS, IMPLICATIONS FOR MATCHING WITH UNRELATED DONORS

A. G. Smith,¹ M. Malki,² E. W. Petersdorf,² S. Warnock,¹ S. McKinney,¹ L. Regen,¹ J. A. Hansen.²

¹Clinical Immunogenetics, Seattle Cancer Care Alliance, Seattle, WA; ²Human Immunogenetics, Fred Hutchinson Cancer Research Center, Seattle, WA

Analysis of B*35 allele level matching among patients and unrelated donors submitted to the Hematopoietic Stem Cell Transplant Component of the 13th International Histocompatibility Workshop showed that 6% of B*3501–positive patients had a B*35 allele mismatched unrelated donor. In contrast, B*3502, 3503 and 3508–positive patients were 4 to 12 times more likely to have B35 allele mismatched donors. To better understand factors impacting B*35 allele matching, we investigated the B*35 allele frequencies and haplotype linkage disequilibrium among 500 patients prospectively typed prior to unrelated hematopoietic stem cell transplantation and for whom sufficient family members were available to assign HLA–A, B, C, DRB1, DQB1 haplotypes. 5 unique B*35 alleles were detected among 88 patients, B*3501 (n = 46), B*3502 (n = 8), B*3503 (n–21), B*3508 (n = 11) and B*3517 (n = 2). All B*35 alleles showed strong linkage with Cw*04 (88%), although B*3502 also associated with Cw*06 (n = 2) and B*3503 with Cw*1203 (n = 2). B*3501 was associated with 16 different DRB1 alleles, most frequently with DRB1*0101 (n = 18). B*3502 showed strong linkage with DRB1*1104 (n = 6), but exhibited haplotype diversity at HLA–A and C loci. B*3503 was associated with 15 different DRB1 alleles, with DRB1*1201/06 and DRB1*0701 most frequent (n = 3 each). B*3508 was linked with 7 different DRB1 alleles, with DRB1*0403 (n = 3) most frequent. Both B*3517–positive individuals carried the haplotype A*0201, B*3517, Cw*04, DRB1*0802, DQB1*0402. 9 of B*3501 haplotypes were detected more than once, while 26 (50%) were unique. Most frequent were A*0201 or A*0301 with B*3501, Cw*04, DRB1*0101, DQB1*0501 (n = 4 each). All B*3502, B*3503 and B*3508 haplotypes were unique. These results reveal that linkage disequilibrium across the MHC differs between B*35 alleles and suggests that patients with alleles other than B*3501 may be more likely to have mismatched donors without prospective allele level typing prior to transplantation. Understanding the likelihood of optimal HLA matching can assist in unrelated donor selection strategies, especially in urgent clinical situations.