P. Y. Lin

Discovery of HLA‐B*480102 in Taiwanese

Human leucocyte antigen (HLA)‐B48, an antigen within 7C CREG (cross‐reacting group) ( Steiner et al., 2001 ) that cross‐reacts frequently with HLA‐B40 (i.e. HLA‐B60 and ‐B61) group of antibodies serologically, can be found in Alaskan Natives ( Leffell et al., 2002 ), Amerindians ( Martinez‐Naves et al., 1997 ), African Americans, Caucasians, and Oriental ethnicities ( Mori et al., 1997 ; Schipper et al., 1997 ; Cao et al., 2001 ; Middleton et al., 2004 ; Hong et al., 2005 ; Itoh et al., 2005 ; Lee et al., 2005 ; Ogata et al., 2007 ). Sequencing investigations demonstrated that the common allele encoding the B48 antigen is B*4801 ( Belich et al., 1992 ). To date, there are at least 16 WHO recognized B*48 alleles according to the most recent report from the WHO nomenclature committee ( Marsh et al., 2005 ). Here we report a newly discovered allele B*480102, a variant of B*4801, detected in a 55‐year‐old Taiwanese patient of Minan origin (southern China).

Determination of HLA-A, -B and -DRB1 haplotypes based on allelic homozygosity data in selected bone marrow donors of the Taiwanese marrow donor registry

From 120 unrelated Taiwanese marrow stem cell donors with allelic homozygosities at human leucocyte antigen (HLA)‐A, ‐B and ‐DRB1 loci, we determined 85 distinguishable haplotypes. Using the predetermined haplotype data, we deduced 418 haplotypes from 1903 unrelated individual stem cell donors selected for HLA confirmatory test. Eighteen of the 20 (90%) most frequently observed haplotypes determined in Asian Americans using computer prediction were found in this study. In comparison with haplotypes determined by maximum likelihood algorithm in Korean population, 18 of the 29 (62.07%) Korean haplotypes with a frequency over 0.5% were also among the haplotypes determined in this investigation. Randomized family studies confirmed that over 50% of the haplotypes observed in the families were among the haplotypes deduced based on allelic homozygosity, suggesting that proportionally additional haplotypes can be determined as the number of donors being studied is increased. Haplotypes carrying low incidence allele characteristics of Taiwanese were also observed in this study. This established haplotype information will be beneficial for patients searching for stem cell donors in our registry domestically and internationally.

Distributions of human leukocyte antigen–A, –B, and –DRB1 alleles and haplotypes based on 46,915 Taiwanese donors

Human leukocyte antigen (HLA)-A, -B, and -DRB1 alleles were typed in 46,915 healthy Taiwanese volunteers recruited for Tzu Chi Taiwan Marrow Donor Registry (TCTMDR). The volunteers were separated into Taiwanese and Taiwanese aborigines. In this study, a total of 51 A, 121 B, and 53 DRB1 alleles were found in the Taiwanese group, and 17 A, 32 B, and 23 DRB1 alleles were identified in the Taiwanese aborigines. Some commonly shared alleles appeared more frequently in one group than in the other. The two haplotypes, among the 20 most frequently observed haplotypes in each group, shared in common by both groups were A*3303-B*5801-DRB1*0301 and A*0207-B*4601-DRB1* 0901. However, both haplotype frequencies in each group were extremely different, indicating the existence of genetic diversity between the two groups. In addition, principal component analysis and clustering results based on high-resolution HLA-A, -B, and -DRB1 alleles indicated that the Taiwanese group was closest to Southern Chinese and reiterated HLA diversity between the Taiwanese and the Taiwanese aborigines. We believe that our findings in this study may provide useful information in search for HLA-matched donors for patients.

Identification of a novel HLA-A allele, A*1131, in a Taiwanese

Here we report the identification and sequence analysis of a new HLA‐A11* variant, A*1131 allele, found in a Taiwanese volunteer bone marrow donor. The novel A*11 variant is identical to A*1125 in exon 2 but differs from A*1125 in exon 3 by one nucleotide substitution at position 527 causing an amino acid change at codon 152 E→V (GAG→GTG). In comparison with HLA‐A*110101, allele A*1131 has three nucleotide differences in exon 3: 527 C→T, 538 C→T and 539 A→T leading to two amino acid variations at residues 152 A→V and 156 Q→L.

Detection of a novel HLA-B27 allele, B*2740, in Taiwanese volunteer bone marrow donors by sequence-based typing: curiosity rewarded.

We report here a novel HLA‐B allele, B*2740, discovered in Taiwanese volunteer marrow donors. The new sequence has nucleotide variation at position 527 (T→A) as compared to B*2708. The nucleotide change caused an amino acid substitution from valine (V) to glutamic acid (E) at codon 152. Since B*2740 carries sequence confers to HLA‐Bw6 public epitope we believe that this novel B*27 allele might have been generated from a gene conversion involving a Bw4‐specific allele (probably B*2704) and a Bw6‐specific allele.

A novel HLA-B allele, B*5214, detected in a Taiwanese volunteer bone marrow donor using a sequence-based typing method.

HLA‐B*5214, a novel rare allele of HLA‐B*52 variant, was found in a Taiwanese volunteer bone marrow donor by sequence‐based typing method. The sequence of B*5214 is identical to that of B*520101 in exon 2 but differs from B*520101 in exon 3 at nucleotide positions 419 A→T and 435 A→G. Alteration of these two nucleotides resulted an amino acid substitution at amino acid residue 116 Y→F ( TAC→TTC) and a silent exchange at residue 121 K→K (AAA→AAG).

Associations among birth weight, placental weight, gestational period and product quality indicators of umbilical cord blood units

INTRODUCTIONnNumbers of CD34+ cell and total nucleated cell (TNC) and cord blood volume are commonly used as indicators for haematopoietic potential of umbilical cord blood (UCB) units. The purpose of this study was to investigate the relationship between donor-related factors and the quality indicators of UCB.nnnMETHODSnObstetric and neonatal clinical laboratory data of a total of 1549 UCB units were obtained from Buddhist Tzu Chi Stem Cells Center (BTCSCC) Cord Blood Bank. A retrospective multivariate analysis was conducted to analyze the data.nnnRESULTSnOur results showed that birth weight had positive correlations with each of the clinical features of CD34+ cell number, TNC count and unit volume of UCB, followed by the placental weight. Longer gestational period would decrease CD34+ cell number and volume of UCB. Female baby and mode of vaginal delivery of neonates were found to have larger amount of TNC in UCB.nnnCONCLUSIONnOur results would be helpful and beneficial in building up standard criteria for evaluating stored UCB units.

Discovery of the novel HLA‐DRB1*09:01:08 allele in a Taiwanese volunteer bone marrow donor and identification of the probable HLA‐A, HLA‐B and HLA‐DRB1 haplotype in association with DRB1*09:01:08

We report here the novel variant of HLA‐DRB1*09:01, DRB1*09:01:08, discovered in a Taiwanese volunteer bone marrow donor by a sequence‐based typing (SBT) method. The DNA sequence of DRB1*09:01:08 is identical to the sequence of DRB1*09:01:02 in exon 2 except a silent mutation at nucleotide position 261(C→T) (GCC→GCT at codon 58). We hypothesize DRB1*09:01:08 was probably derived from DRB1*09:01:02 via a nucleotide point mutation event. The plausible HLA‐A, HLA‐B and HLA‐DRB1 haplotype in association with DRB1*09:01:08 was deduced as A*02:07‐B*46:01‐DRB1*09:01:08.

Human adipose-derived stem cells for the treatment of intracerebral hemorrhage in rats via femoral intravenous injection

Human adipose-derived stem cells (huADSC) were generated from fat tissue of a 65-year-old male donor. Flow cytometry and reverse transcription polymerase chain reaction (RT-PCR) analyses indicated that the huADSC express neural cell proteins (MAP2, GFAP, nestin and β-III tubulin), neurotrophic growth factors (BDNF and GDNF), and the chemotactic factor CXCR4 and its corresponding ligand CXCL12. In addition, huADSC expressed the characteristic mesenchymal stem cell (MSC) markers CD29, CD44, CD73, CD90, CD105 and HLA class I. The huADSC were employed, via a right femoral vein injection, to treat rats inflicted with experimental intracerebral hemorrhage (ICH). Behavioral measurement on the experimental animals, seven days after the huADSC therapy, showed a significant functional improvement in the rats with stem cell therapy in comparison with rats of the control group without the stem cell therapy. The injected huADSC were detectable in the brains of the huADSC treated rats as determined by histochemistry analysis, suggesting a role of the infused huADSC in facilitating functional recovery of the experimental animals with ICH induced stroke.

Discovery of the novel HLA-DRB1*16:16 allele in a Taiwanese unrelated bone marrow stem cell donor by a sequence-based typing method and the probable haplotype associated with DRB1*16:16

We report here a de novo HLA‐DRB1 allele, DRB1*16:16, discovered in a Taiwanese unrelated volunteer bone marrow stem cell donor by a sequence‐based typing (SBT) method. In exon 2, the DNA sequence of DRB1*16:16 is identical to the sequence of DRB1*16:02:01 except the nucleotides at positions 258 (C→T), 260 (C→A) and 261 (T→G). The nucleotide substitution produced an amino acid replacement at residue 58 (A→E). The formation of DRB1*16:16 was probably generated by a DNA sequence recombination event involving DRB1*11:01:01 and DRB1*16:02:01. The probable HLA‐A, ‐B and ‐DRB1 haplotype in association with DRB1*16:16 may be deduced as A*02‐B*38‐DRB1*16:16.