Similar Datasets
Project description:HLA-DR-lacking HSPCs [HLA-DR(-) HSPCs] were detected in aplastic anemia (AA) patients with HLA-DR15. HLA-DR(-) HSPCs may evade the attack by CD4+ T-cells recognizing the autoantigen presented by HLA-DR15. The goal of this study is to clarify the immune escape mechanisms from antigen-specific T-cells by comparing the trranscriptome profile of HLA-DR(+) HSPCs and HLA-DR(-) HSPCs.
2022-05-31 | GSE183768 | GEO
Project description:Leprosy is a chronic granulomatous disease caused by infection with Mycobacterium leprae. Genetic association studies indicated that leprosy risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but the full number of variants in this region has yet to be elucidated. To identify further susceptibility loci or loss of function variants for this disease, we performed fine-mapping analysis of the MHC region using a Han Chinese reference panel (n= 10,689 patients, 29,948 genetic markers) in the data sets from our previous leprosy studies. Then, a fixed-effect meta-analysis was carried out separately for Chinese (case=2,901, control=3,801) and North Chinese (case=1,983, control=2,635) participants. The meta-analysis of Chinese participants identified 10 HLA-type or amino acid variants with lower than the genome-wide significant susceptibility signal. Next, gene-by-gene step-wise conditional analysis was performed in the combined dataset of these cohorts. Finally, we identified four new independent susceptibility loci (HLA-DQA1, HLA-C, rs3129063, and rs58327373) and confirmed one previously reported locus (HLA-DRB1) that significantly associated with leprosy in the Chinese Han population. Thus the results of this study increase knowledge about leprosy risk variants and illustrate the value of HLA imputation for fine mapping of causal variants in the MHC.
2018-09-30 | GSE119367 | GEO
Project description:Myeloid-derived suppressor cells (MDSC) is a heterogeneous population of cells that can negatively regulate T-cell function. As opposed to murine MDSC, which are characterized as Gr-1+CD11b+ cells, human MDSC are not so clearly defined due to lack of specific markers. Our lab has previously identified a new subset of MDSC as CD14+HLA-DR-neg/low cells from PBMC. CD14+HLA-DR-neg/low MDSC not only suppress proliferation and IFN-gamma secretion of autologous T cells, but also induce CD25+Foxp3+ regulatory T cells that are suppressive in vitro, whereas the counterpart CD14+HLA-DR-high monocytes don’t have the effect. In this study, we compare the immune-related gene expression between CD14+HLA-DR-neg/low MDSC and CD14+HLA-DR-high monocytes to better characterize the difference between these two populations and to find new potential specific marker for human MDSC. PBMC were isolated from fresh blood healthy donor by density centrifugation. CD14+ cells were isolated by AutoMACS CD14 microbeads using a AutoMACS (Miltenyi), and then stained with CD14 and HLA-DR antibodies. MDSC and monocytes control cells were sorted as CD14+ HLA-DR-neg/low and CD14+HLA-DR-high cells respectively. The sorted two populations were immediately frozen in liquid nitrogen and shipped to the company on dry ice for RNA isolation and further microarray.
2011-09-08 | E-GEOD-32001 | biostudies-arrayexpress
Project description:HLA-DRB1 alleles have been associated with several autoimmune diseases. In anti-citrullinated protein antibody positive rheumatoid arthritis (ACPA-positive RA), HLA-DRB1 shared epitope (SE) alleles are the major genetic risk factors. In order to investigate whether expression of different alleles of major histocompatibility complex (MHC) Class II genes influence functions of immune cells, we investigated transcriptomic profiles of a variety of immune cells from healthy individuals carrying different HLA-DRB1 alleles. Sequencing libraries from peripheral blood mononuclear cells, CD4+ T cells, CD8+ T cells, and CD14+ monocytes of 32 genetically pre-selected healthy female individuals were generated, sequenced and reads were aligned to the standard reference. For the MHC region, reads were mapped to available MHC reference haplotypes and AltHapAlignR was used to estimate gene expression. Using this method, HLA-DRB and HLA-DQ were found to be differentially expressed in different immune cells of healthy individuals as well as in whole blood samples of RA patients carrying HLA-DRB1 SE-positive versus SE-negative alleles. In contrast, no genes outside the MHC region were differentially expressed between individuals carrying HLA-DRB1 SE-positive and SE-negative alleles. Existing methods for HLA-DR allele-specific protein expression were evaluated but were not mature enough to provide appropriate complementary information at the protein level. Altogether, our findings suggest that immune effects associated with different allelic forms of HLA-DR and HLA-DQ may be associated not only with differences in the structure of these proteins, but also with differences in their expression levels.
2020-12-22 | GSE163605 | GEO
Project description:Background. Assessment of non-HLA variants alongside standard HLA testing was previously shown to improve the identification of potential coeliac disease (CD) patients. We intended to identify new genetic variants associated with CD in the Polish population that would improve CD risk prediction when used alongside HLA haplotype analysis. Results. Association analysis using four HLA-tagging SNPs showed that, as was found in other populations, positive predicting genotypes (HLA-DQ2.5/DQ2.5, HLA-DQ2.5/DQ2.2, and HLA-DQ2.5/DQ8) were found at higher frequencies in CD patients than in healthy control individuals in the Polish population. Both CD-associated SNPs discovered by GWAS were found in the CD susceptibility region, confirming the previously-determined association of the major histocompatibility (MHC) region with CD pathogenesis. The two most significant SNPs from the GWAS were rs9272346 (HLA-dependent; localized within 1 Kb of DQA1) and rs3130484 (HLA-independent; mapped to MSH5). Specificity of CD prediction using the four HLA-tagging SNPs achieved 92.9%, but sensitivity was only 45.5%. However, when a testing combination of the HLA-tagging SNPs and the MSH5 SNP was used, specificity decreased to 80%, and sensitivity increased to 74%.
2015-10-15 | GSE65424 | GEO