Tissue antigens最新文献

The novel HLA-DRB1*14:143 allele differs from DRB1*14:10 by two nucleotide substitutions at positions 344 and 345 of exon 2.

To investigate the relationship between human leukocyte antigen (HLA) class I and II alleles and treatment-induced anemia in chronic hepatitis C (CHC) patients receiving combination therapy with pegylated interferon-α (PEG-IFN-α) and ribavirin (RBV). One hundred six naïve CHC patients (59 females and 47 males; mean age, 53.08 years) who underwent combination treatment were enrolled. The patients were considered positive for hemoglobin (Hb)-related side effects if the Hb concentrations dropped below 10 g/dl during PEG-IFN-α plus RBV treatment. The HLA-A, -B, -C, -DR, and -DQ loci were investigated by sequence-based genotyping. The effects of the clinical characteristics, virologic variables, and the HLA alleles on treatment-induced anemia were evaluated by a logistic regression analysis. Forty patients (37.7%) had Hb levels below 10 g/dl during the treatment course. Low baseline Hb levels and an advanced liver fibrosis stage were associated with decreases in Hb levels to below 10 g/dl. The occurrence of treatment-related anemia (Hb < 10 g/dl) was significantly associated with HLA-B*15:02 as shown by multivariate analysis (adjusted odds ratio, 8.13; 95% confidence interval: 1.19-55.70; P-value after Holm's procedure, 0.03). HLA-B*15:02 is associated with treatment-induced anemia in Taiwanese CHC patients receiving combination therapy with PEG-IFN-α plus RBV.

Distinct human leukocyte antigen (HLA) allele and haplotype distributions occur in the northern and southern Han populations of China. However, different ethnic groups in China show limited regional distributions for many HLA alleles and haplotypes. Therefore, it is necessary and meaningful to study the differences in HLA allele and haplotype distribution for northern and southern ethnic groups of China. A total of 428 unrelated individuals from the Lisu, Nu, Tu and Yugur ethnic populations were genotyped for HLA-A, -B, -C and -DRB1 alleles using the PCR-Luminex typing method. The frequencies of HLA alleles and statistically inferred haplotypes were calculated. A total of 29 HLA-A, 54 HLA-B, 27 HLA-C and 41 HLA-DRB1 alleles were spread throughout these four populations with distinct allele and deduced haplotype frequencies between populations. Some alleles and deduced haplotypes exhibited significantly different distributions between northern (Tu and Yugur) and southern groups (Lisu and Nu). A phylogenetic tree and principal component analysis were used to compare the HLA polymorphism between our dataset and 19 other eastern and southeastern Asian populations. This analysis showed that Lisu and Nu belong to a cluster of southern ethnic groups, while Tu and Yugur are most closely related to other northern groups. Thus, distinct ethnic population histories were revealed by analyzing HLA allelic polymorphisms with the HLA profiles of the Lisu and Nu southern Chinese ethnic groups clearly different from the Tu and Yugur northern ethnic groups. The results will be useful for future association studies of infectious disease and contribute toward a more efficient search of organ/tissue matches for transplantation.

RNA interference (RNAi) has been a landmark discovery in science. A typical application is to knock down the expression of endogenous genes by delivering small interfering RNA (siRNA) into cells triggering the degradation of complementary mRNA. However, RNAi can also be exploited the other way round: making use of the huge diversity of endogenous microRNAs (miRNA), the expression of exogenously introduced genes tagged with artificial miRNA target sequences can be negatively regulated according to the activity of a given miRNA which can be tissue-, lineage-, activation- or differentiation stage specific. This has significantly expanded the regulatory potential of gene transfer vectors and will benefit both basic science and therapeutic applications. This review briefly introduces the reader to the technical basis for exploiting miRNA regulation, followed by a discussion of specific applications for miRNA-regulated vectors/viruses in basic research, gene- and virotherapy.

Donor human leukocyte antigen (HLA)-specific antibodies (Abs) with the ability to activate complement are associated with an increased risk of early Ab-mediated rejection (AMR) of kidney allografts. In recent years, also non-HLA Abs-binding endothelial cells have been shown to elicit early AMR. Donor-specific anti-endothelial cell Abs escape detection in the pre-transplant evaluation if only lymphocytes are used as target cells in crossmatch tests. We addressed whether endothelial precursor cells (EPCs) could be used for detection of complement-fixing as well as non-fixing Abs and if complement factor and immunoglobulin G (IgG) deposition on co-purified T and B cells correlated to the outcome of the T- and B-cell complement-dependent cytotoxicity assay. Deposition of complement factors C3c and C3d, but not C1q nor C4d, were detected on EPCs and lymphocytes upon incubation with HLA Ab-positive sera. There was a correlation between the amount of C3c deposition and IgG binding on EPCs (R(2) = 0.71, P = 0.0012) and T cells (R(2) = 0.74, P = 0.0006) but not for B cells (R(2) = 0.34, P = 0.059). The specificity and sensitivity for C3d deposition on endothelial precursor cell crossmatch (EPCXM) T cells vs the T complement-dependent cytotoxicity (CDC) assay were 69% and 72%, respectively. The EPCXM B-cell C3d assay had considerably lower sensitivity (39%) than the B CDC assay. Altogether, this novel assay based on the detection of complements factors on EPCs and lymphocytes by flow cytometry may widen the diagnostic repertoire and thereby improve the clinical management of patients undergoing kidney transplantation.

Although the role of CD14 in recognizing Mycobacterium tuberculosis is well-understood, the possible role of polymorphisms in susceptibility to develop tuberculosis remains unclear. This study evaluates whether there is an association of polymorphisms within the promoter of the CD14 gene with susceptibility to pulmonary tuberculosis. In a case-control study, we genotyped the eight known single nucleotide polymorphisms SNPs within the promoter of the CD14 gene of 698 Han Chinese subjects. Statistically significant differences between tuberculosis patients and healthy controls were found for G-1619A, T-1359G, A-1145G, and C-159T. The haplotype-GGGT, composed of these four SNPs, exhibited a significant association with the disease. Furthermore, expression levels of soluble CD14 were significantly higher in tuberculosis patients with the GGGT haplotype than with other haplotypes, while IgE expression levels were significantly reduced. Our results suggest that these four SNPs within the promoter of the CD14 gene are associated with susceptibility to pulmonary tuberculosis.

The chemokine receptor [C-C chemokine receptor 5 (CCR5)] is expressed on diverse immune effecter cells and has been implicated in the pathogenesis of rheumatoid arthritis (RA). This study sought to determine whether single-nucleotide polymorphisms (SNPs) in the CCR5 gene and their haplotypes were associated with susceptibility to and severity of RA. Three hundred fifty-seven patients with RA and 383 healthy unrelated controls were recruited. Using a pyrosequencing assay, we examined four polymorphisms -1118 CTAT(ins) (/del) (rs10577983), 303 A>G (rs1799987), 927 C>T (rs1800024), and 4838 G>T (rs1800874) of the CCR5 gene, which were distributed over the promoter region as well as the 5' and 3' untranslated regions. No significant difference in the genotype, allele, and haplotype frequencies of the four selected SNPs was observed between RA patients and controls. CCR5 polymorphisms of -1118 CTAT(del) (P = 0.012; corrected P = 0.048) and 303 A>G (P = 0.012; corrected P = 0.048) showed a significant association with radiographic severity in a recessive model, and, as a result of multivariate logistic regression analysis, were found to be an independent predictor of radiographic severity. When we separated the erosion score from the total Sharp score, the statistical significance of CCR5 polymorphisms showed an increase; -1118 CTAT(ins) (/del) (P = 0.007; corrected P = 0.028) and 303 A>G (P = 0.007; corrected P = 0.028). Neither SNPs nor haplotypes of the CCR5 gene showed a significant association with joint space narrowing score. These results indicate that genetic polymorphisms of CCR5 are an independent risk factor for radiographic severity denoted by modified Sharp score, particularly joint erosion in RA.

The human leukocyte antigen (HLA)-A*24:96 allele differs from the closest matching allele A*24:01:01:01 by three nucleotide substitutions in exon 3 at nt 411(C->T), nt 412(C->A) and nt 419(A->T).

Prosthetic joint infection (PJI) is a serious complication of the total joint arthroplasty (TJA). Serum mannose-binding lectin (MBL), a pattern recognition receptor, is involved in antibacterial immune response. This study investigated whether functional variants of the MBL2 gene may be associated with the risk of PJI. MBL2 -550 (H/L, rs11003125), MBL2 -221 (Y/X, rs7096206) and MBL2 +54 (G/A, rs1800450) single nucleotide polymorphisms (SNP) were genotyped in 112 PJI patients and two control groups: 245 patients with aseptic TJA and 196 Czech population controls without TJA. Serum MBL concentration was assessed in PJI patients (n = 92) and aseptic TJA controls (n = 56). The distribution of MBL2 genotypes complied with the Hardy-Weinberg equilibrium in all investigated groups. Importantly, MBL2 -550 L allele (allelic frequency, 0.72) and LL genotype (genotype frequency, 0.51) were more frequent among PJI patients compared to aseptic TJA controls (L allele: 0.63, P = 0.016, P(c) = 0.048; LL genotype: 0.39, P = 0.037, P(c) > 0.05) and to Czech population controls (L allele: 0.61, P = 0.010, P(c) = 0.030; LL genotype: 0.35, P = 0.006, P(c) = 0.018), respectively. Regarding MBL protein, the MBL2 -550 L carriers presented with lower serum MBL concentrations than non-carriers (median; 593 vs 1876 ng/ml; P < 0.01). Similarly, the carriage of MBL2 -221 X and 54 A alleles was associated with lower serum MBL concentrations (P < 0.01). In conclusion, MBL2 -550 genetic variant(s) associated with low serum concentration of MBL protein can increase the risk of PJI.

Hashimoto disease (HD) is an autoimmune thyroid disease resulting from complex interactions between genetic and environmental factors. The human leukocyte antigen (HLA) gene has been established to be involved in the susceptibility to HD. We aim to investigate the associations between HLA-B alleles and Han Chinese children with HD by both case-control and family-based studies. A total of 108 unrelated children with HD, 380 unrelated healthy controls, 58 trios of affected patients and their parents, and 75 trios of unaffected siblings and their parents were recruited. HLA-B genotyping was performed by polymerase chain reaction and detected with a sequence-specific oligonucleotide probes system. We found that B*46:01 allele (OR = 2.31, 95% CI 1.60-3.34, P(c) = 9.99 × 10(-5)) and carrier (OR = 3.28, 95% CI 2.10-5.11, P(c) = 1.35 × 10(-6)) were associated with HD risk. Transmission/disequilibrium test further confirmed an overtransmission of the B*46:01 (OR 2.55, 95% CI 1.36-6.10, P = 6.5 × 10(-3)). The findings were similar in females when stratified by gender. In conclusion, our results clearly identify that HLA-B*46:01 confers susceptibility to HD in Han Chinese children. Further studies with larger children cohort are required to confirm the role of B*46:01 in the development of HD.