X. Shan

High-Resolution Analyses of Human Leukocyte Antigens Allele and Haplotype Frequencies Based on 169,995 Volunteers from the China Bone Marrow Donor Registry Program

Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169,995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis studies.

Prevalence of platelet-specific antibodies and efficacy of crossmatch-compatible platelet transfusions in refractory patients

The development of specific antibodies against human leukocyte antigen (HLA) and/or human platelet antigen (HPA) could induce platelet transfusion refractoriness especially in patients receiving multiple platelet transfusions. A retrospective analysis was conducted to evaluate the prevalence of platelet‐specific antibodies and the efficacy of crossmatch‐compatible platelet transfusions in these recipients.

Identification of a novel HLA-B allele, HLA-B*3713, in a Chinese individual.

A novel human leukocyte antigen (HLA) class I allele, HLA-B*3713, has been identified in a Chinese individual. The HLA-B*3713 allele differs from the closest matching allele B*370101 by one nucleotide substitutions in exon 3 at nt 527(T-->A), resulting in an amino acid change from Val (GTG) to Glu (GAG) at codon 152.

Sequence‐based typing identified a new HLA‐B*40 allele, HLA‐B*40:124:02

The sequence of a novel allele, HLA-B*40:124:02, differs from HLA-B*40:42 by three-nucleotide exchanges in exon 3.

Identification of a novel HLA-B allele HLA-B*55:34 in a Chinese individual

The HLA-B*55:34 allele differs from the closest matching allele B*55:02:01 by one nucleotide substitution in exon 2.

Identification of a novel HLA‐B allele HLA‐B*13:20 in a Chinese individual

The HLA-B*13:20 allele differs from the closest matching allele B*13:01:01 by one nucleotide substitution in exon 3 at nt 527 (T→A).

A novel HLA‐C*15 allele, HLA‐C*15:02:04

HLA-C*15:02:04 differs from HLA-C*15:02:01 by the nucleotide exchange at position 143.

The novel allele HLA-A*02:145 differs from HLA-A*02:01:01 by a single amino acid exchange at position 153 from alanine to valine

HLA-A*02:145 differs from HLA-A*02:02:01:01 by the amino acid exchange at position 153 Ala changes to Val.

A novel HLA-DRB1 allele, DRB1*08:36, identified by sequence-based typing.

A novel human leukocyte antigen (HLA)-DRB1 allele, DRB1*08:36, has been identified during routine sequence-specific oligonucleotide (SSO) typing and sequence-based typing (SBT) in a sample from a registered donor of Chinese Marrow Donor Program. The DRB1*08:36 allele differs from the closest related DRB1*08:03:02 allele by one nucleotide substitution in exon 2, at position 181 which results in an amino acid replacement at codon 32. Tyr is exchanged for His in the novel allele. These findings add a novel member to the HLA-DRB1*08 family.

Identification of a novel HLA‐DRB allele, HLA‐DRB1*1461

We describe the identification of a new DRB1*14 allele, DRB1*1461, found in a Chinese individual. The novel allele has been identified in routine polymerase chain reaction-sequence-specific oligonucleotide and sequence-based typing. The nucleotide sequence of DRB1*1461 is identical to DRB1*1404 except for a single substitution in codon 16 (TAT-->CAT), leading to a change from Tyr to His.