Tissue antigens最新文献

The protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene has, during the last 2 years, been recognized as a susceptibility gene for numerous autoimmune diseases, including rheumatoid arthritis (RA) and type 1 diabetes. An association between the exonic 1858C>T single nucleotide polymorphism (SNP) and RA has repeatedly been replicated in several Caucasian populations. The SNP is not associated with autoimmune diseases in Asian populations, as the 1858T allele is almost absent. Recently, a promoter polymorphism -1123G>C was proposed to be associated with acute-onset type 1 diabetes in Japanese and Korean populations. Furthermore, in Caucasian populations, the presence of additional PTPN22 risk variants has been suggested, indicating that the 1858C>T risk variant cannot explain the entire disease association observed in the region. In this study, we wanted to jointly address and integrate these separate findings to further elucidate the association between the PTPN22 gene and RA in a Norwegian material of 861 RA patients and 559 healthy controls. Our results revealed that the strength of the association with the PTPN22 promoter polymorphism, -1123G>C, is analogous to that observed for 1858C>T. As the -1123G>C variant is also polymorphic in Asian populations, our data underpin the need to further explore the association between this variant and autoimmune diseases in different populations.

Granzyme B is a 247 amino acid pro-apoptotic protease secreted by effector lymphocytes for the purpose of killing virus-infected cells. While the capacity of granzyme B to potently induce caspase-dependent apoptosis has long been recognized, it has only recently been found that human and mouse granzyme B activate overlapping but distinct apoptotic pathways. To investigate a possible evolutionary basis for this observation, we sequenced the exons and flanking intronic sequences of the mouse Gzmb gene from a variety of inbred laboratory strains and wild mice. The sequences of 12/13 inbred strains encoded identical proteins, the exception being DBA/2, whose sequence varied at two amino acids. By contrast with the laboratory strains, there was extensive polymorphism in the Gzmb gene of 54 wild mice and 28 wild-derived inbred mice examined, resulting in 2-18 amino acid differences in the predicted proteins, a discrepancy rate of up to 7.3%. Many of these amino acid variations were found in rat and/or human granzyme B. The granzyme B allotype of inbred laboratory strains could be identified in only one of three geographically dispersed clans of wild mice and was absent from all 28 wild-derived inbred strains. The Gzmb gene of Mus musculus castaneus, a close relative of laboratory mice, encoded six amino acid differences compared with the laboratory strains, all of which were also found in corresponding positions in the granzyme B molecules of wild mice. Unlike the protease, the extended granzyme B recognition and cleavage site in Bid, a key pro-apoptotic substrate, was invariant.

We report here the identification of a novel human leukocyte antigen-A*2468 allele that was detected by polymerase chain reaction sequence-based typing.

A novel A*68020103 allele was completely characterized by sequencing in a Spanish bone marrow donor. A*68020103 has an eight nucleotides deletion at the 5'-end of intron 2, when compared with other A*6802 alleles. This alteration does not affect either its mRNA splicing process or serological detection.

In solid tumors, human leucocyte antigen (HLA)-A2 has been suggested to be a risk factor and a negative prognostic factor. The HLA-A2 allele in Scandinavia has a high prevalence; it decreases with latitude and also with ovarian cancer mortality in Europe. Furthermore, an association of the HLA-A2 allele with severe prognosis in serous adenocarcinoma of the ovary in stages III-IV was found. Thirty-two unrelated Swedish women with relapsing or progressive ovarian cancer were analysed for the genotypes at the HLA-A, HLA-B, HLA-Cw, and HLA-DRB1 loci by the polymerase chain reaction/sequence-specific primer method. The frequencies of HLA alleles of healthy Swedish bone marrow donors provided by the coordinating centre of the Bone Marrow Donors Worldwide Registries, Leiden, the Netherlands were used as controls. When this cohort of epithelial ovarian cancer patients was compared with healthy Swedish donors, the frequency of HLA-A1 and HLA-A2 gene/phenotype appears, although not statistically significant, to be increased in patients with ovarian carcinoma, while HLA-A3 was decreased. HLA-A2 homozygotes were twofold higher in patients. The A2-B8 haplotype was significantly increased (corrected P value). A2-B5, A2-B15, A2-DRB1*03, A2-DRB1*04, A2-B15-Cw3, and A2-B8-DRB1*03 had odds ratio as well as the level of the lower confidence interval above 1 and significant P value only when considered as single, non-corrected analysis. HLA-B15 and HLA-Cw3 were only present in HLA-A2-positive patients showing that the HLA-A2-HLA-Cw3 and HLA-B15 haplotypes were segregated. In this selected cohort with advanced disease, there are indications of an unusual overrepresentation of HLA class I and II genes/haplotypes as well as segregation for the HLA-A2-HLA-Cw3 and HLA-B15 haplotypes. These findings are presented as a descriptive analysis and need further investigations on a larger series of ovarian cancer patients to establish prognostic associations.

The distribution of human leukocyte antigen (HLA)-DRB1-DQA1-DQB1 haplotypes was analyzed separately in two distinct French ethnic groups with type I diabetes (T1D), i.e. French North African migrants (n= 64, mean age at diagnosis = 8.25 years) and ancient French natives (n= 60, mean age at diagnosis = 7.42 years). HLA associations were determined by calculating odds ratios (ORs) between patients and two ethnic-matched control populations. Results show highly similar ORs for the conservative DRB1*0301-DQA1*0501-DQB1*0201 haplotype of susceptibility (OR: 3.22 and 3.93 in migrants and natives, respectively) and the DRB1*1501-DQA1*0102-DQB1*0602 haplotype of resistance (OR: 0.05 and 0.03, respectively). In contrast, among the more variable DRB1*04-DQB1*0302 haplotypes of susceptibility, the DRB1*0402 (OR: 3.10 and 32.84) and 0405 (OR: 5.90 and 16.25, respectively) were associated with T1D in migrants and natives, whereas an increase of DRB1*0401, a rare allele in migrants, was significant in natives only. Also, among the DRB1*11-DQA1*0505-DQB1*0301 haplotypes of resistance, the OR observed for DRB1*1104-DQA1*0505-DQB1*0301, common in migrants, was lower (OR: 0.08) than for DRB1*1101-DQA1*0505-DQB1*0301 (OR: 0.32), common in natives. How DRB1*11 subtypes might affect differently the risk conferred by DQA1*0505-DQB1*0301 will be discussed.

The aim of this study was to evaluate the association between systemic lupus erythematosus (SLE) and polymorphisms in the interleukin-23 receptor (IL23R) gene, which have been previously found to be associated with two autoimmune diseases: inflammatory bowel disease and psoriasis. Our study includes 224 SLE patients and 342 healthy controls. The genotyping of IL23R variants was carried out using a polymerase chain reaction system with predeveloped TaqMan allelic discrimination assays. No statistically significant differences were observed between SLE patients and healthy controls with any of the IL23R genetic variants. In addition, we did not find any significant differences when we stratified SLE patients according to their clinical and demographic features. These results suggest that IL23R polymorphisms do not appear to play an important role in the susceptibility or severity of SLE in the Spanish population.

The -168A-G polymorphism has been shown to influence transcription of the MHC2TA gene and has been implicated in several inflammatory/autoimmune disorders. Attempts to reproduce these findings have been inconclusive. We investigated the role of this promoter single nucleotide polymorphism (SNP) in 440 multiple sclerosis (MS), 293 rheumatoid arthritis (RA), 74 juvenile idiopathic arthritis (JIA) patients and 316 healthy controls from Northern Ireland. We also genotyped a non-synonymous SNP in exon 11, +1614G/C. There was no significant difference in the -168G allele frequencies and carriage rates in the separate RA, JIA, or MS collections compared with the control group [odds ratio (OR) = 1.1, 95% confidence intervals (CI) = 0.86-1.44; OR = 1.1, 95% CI = 0.75-1.68; OR = 1.1, 95% CI = 0.84-1.35, respectively]. Assessment of the common phenotype (chronic inflammatory disease; n = 807 vs 316 controls) was negative as well. Carriage of +1614C was protective against JIA (OR = 0.6, 95% CI = 0.3-1.0) and showed a similar trend in RA and MS (OR = 0.7, 95% CI = 0.5-1.0; OR = 0.8, 95% CI = 0.6-1.0, respectively). The common phenotype (chronic inflammatory disease) was also significant (OR = 0.7, 95% CI = 0.6-1.0).

Exons 2 through 9 of KIR3DL2 were amplified from genomic DNA from 79 bone marrow transplantation patients and their unrelated donors. Sequencing of heterozygotes and isolated alleles identified 9 of the 17 known alleles. The alleles provide confirmation of previously submitted sequences and are carried by transformed B-cell lines that can be used as references for assay development. Alleles 3DL2*001, *002, *007 and *009 accounted for 111 of the total 144 possible alleles and were the only ones found in a homozygous state. New alleles (3DL2*017, *018, *019, *020, and *021) were found in seven transplant samples and one workshop cell. This study describes the development of reagents and protocols for sequencing of KIR3DL2 alleles from genomic DNA.

Hereditary hemochromatosis (HH) is one of the most common autosomal recessive genetic disorders of iron metabolism in white populations, which leads to inappropriately high iron absorption. C282Y, H63D, and S65C are three major missense mutations of the hemochromatosis gene (HFE). In the present study, C282Y, H63D, and S65C mutations in 395 normal Chinese Han populations from Zhejiang province were investigated. No C282Y, S65C mutations, and H63D homozygote was observed, while the genotype frequency of H63D heterozygote was 4.6% and the allelic frequency 2.3% in this population. This was the first report to analyze the prevalence of C282Y, H63D, and S65C mutations in the HFE gene in a Chinese Han population. Low incidence of the HFE gene mutations could be a reason for the rarity of HH in the Chinese Han population studied.