Tissue antigens最新文献

Aging is associated clinically with increases in the frequency and severity of infectious diseases and an increased incidence of cancer, chronic inflammatory disorders and autoimmunity. These age-associated immune dysfunctions are the consequence of declines in both the generation of new naïve T and B lymphocytes and the functional competence of memory populations. These alterations collectively are termed immunosenescence.

Recently, a -105G>A promoter polymorphism coding for selenoprotein S (SELS) has been shown to increase proinflammatory cytokine expression. We, therefore, analyzed SELS expression and potential phenotypic consequences of the -105G>A polymorphism in patients with inflammatory bowel disease (IBD). SELS mRNA was measured by quantitative polymerase chain reaction (PCR) in intestinal epithelial cells (IEC) after stimulation with proinflammatory cytokines and in human colonic biopsies of IBD patients as well as in murine models of ileitis and murine cytomegalovirus (MCMV) colitis. Genomic DNA from 563 individuals (Crohn's disease: n = 205; ulcerative colitis: n = 154; controls: n = 204) was analyzed for the presence of the SELS-105G>A polymorphism and the three nucleotide-binding oligomerization domain-containing protein 2 (NOD2)/caspase recruitment domain-containing protein 15 (CARD15) variants p.Arg702Trp, p.Gly908Arg and p.Leu1007fsX1008. SELS mRNA expression was increased in IEC after stimulation with proinflammatory cytokines, while its expression was not significantly altered in murine ileitis and MCMV colitis and in inflamed ileal and colonic lesions in IBD patients compared with normal controls. The SELS-105G>A polymorphism was observed with similar frequencies in IBD patients and controls and was not associated with a certain disease phenotype or serum tumor necrosis factor alpha (TNF-alpha) levels in these patients. Medium serum TNF-alpha was 1.27 pg/ml in IBD patients, while none of the controls had TNF-alpha concentrations above the detection threshold (P < 0.0001). SELS mRNA expression is upregulated by proinflammatory cytokines in IECs but the SELS-105G>A polymorphism is not associated with IBD susceptibility and does not contribute to a certain disease phenotype or increased TNF-alpha levels in IBD patients.

The B*3563 showed a hybrid sequence carrying B*4001-like sequence (exon 2) on B*350101 background.

Sarcoidosis is a heterogeneous disorder, both phenotypically and genetically. Two independent studies have recently shown that a functional polymorphism within butyrophilin-like 2 (BTNL2) gene predisposes to sarcoidosis independently of the human leukocyte antigen (HLA)-DRB1 alleles. However, in both studies, data analysis was not stratified by Löfgren's syndrome, a clinically and genetically distinct sarcoidosis subset. BTNL2, potentially encoding an immune coreceptor, is adjacent and in linkage disequilibrium (LD) with HLA-DRB1. We investigated six BTNL2 variants, including the functional rs2076530 (G > A), as well as HLA-DRB1 alleles, by sequence-specific primers-polymerase chain reaction, in 288 patients and 446 controls from two European countries. In the patient group as a whole, the HLA-DRB1*14 [odds ratio (OR) = 3.1, P(c) = 0.0003], DRB1*12 (OR = 2.5, P(c) = 0.003), and BTNL2 rs2076530 A allele (OR = 1.49, P(c) = 0.002) were all associated with disease susceptibility. However, after exclusion of patients presenting with Löfgren's syndrome and after adjusting for HLA-DRB1 alleles, the association between BTNL2 rs2076530 A and disease disappeared (P = 0.23). By contrast, both HLA-DRB1*14 and DRB1*12 remained strongly significant (OR = 3.60, P < 0.0001 and OR = 3.03, P = 0.003, respectively). BTNL2 haplotype 4, tagged by the rs2076530 G allele, also remained associated with non-Löfgren sarcoidosis after adjusting for HLA-DRB1 alleles (OR 0.37, P = 0.016). In summary, HLA-DRB1*14, DRB1*12, and BTNL2 haplotype 4--but not rs2076530 A--are associated with non-Löfgren sarcoidosis. However, the tight LD across the HLA complex makes it difficult to identify the precise location of the susceptibility locus/i. Larger sample sets from different ethnic groups, finer mapping, and more robust LD analyses across the HLA region are needed.

A novel human leukocyte antigen-A*9206 allele was identified by sequence-based typing in China.

Discovery of the novel HLA-B*5149 allele in a North American Caucasian individual is described. It differs from B*510101 by one nucleotide within the coding sequence of exons 1-6. A substitution at nucleotide position 488 in exon 3 changes alanine to glycine in amino acid position 139.