Human Leukocyte Antigen Family Research Articles

Integrated analysis of single-cell and bulk RNA-sequencing identifies a signature based on T-cell marker genes to predict prognosis and therapeutic response in lung squamous cell carcinoma.

Cancer immunotherapy is an increasingly successful strategy for treating patients with advanced or conventionally drug-resistant cancers. T cells have been proved to play important roles in anti-tumor and tumor microenvironment shaping, while these roles have not been explained in lung squamous cell carcinoma (LUSC). In this study, we first performed a comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data from the gene expression omnibus (GEO) database to identify 72 T-cell marker genes. Subsequently, we constructed a 5-gene prognostic signature in the training cohort based on the T-cell marker genes from the cancer genome atlas (TCGA) database, which was further validated in the testing cohort and GEO cohort. The areas under the receiver operating characteristic curve at 1-, 3-, and 5-years were 0.614, 0.713 and 0.702 in the training cohort, 0.669, 0.603 and 0.645 in the testing cohort, 0.661, 0.628 and 0.590 in the GEO cohort, respectively. Furthermore, we created a highly reliable nomogram to facilitate clinical application. Gene set enrichment analysis showed that immune-related pathways were mainly enriched in the high-risk group. Tumor immune microenvironment indicated that high-risk group exhibited higher immune score, stromal score, and immune cell infiltration levels. Moreover, genes of the immune checkpoints and human leukocyte antigen family were all overexpressed in high-risk group. Drug sensitivity revealed that low-risk group was sensitive to 8 chemotherapeutic drugs and high-risk group to 4 chemotherapeutic drugs. In short, our study reveals a novel prognostic signature based on T-cell marker genes, which provides a new target and theoretical support for LUSC patients.

Serum levels of soluble HLA-G correlate with disease activity in pediatric patients with Crohn's disease.

Background:Human leukocyte antigen (HLA)-G, a member of the HLA family, is crucial for fetomaternal tolerance. Transmembrane or circulating/soluble HLA-G (sHLA-G) is elevated in autoimmune conditions and the tumor microenvironment. Circulating sHLA-G levels and their association with disease activity have not yet been assessed in pediatric patients with inflammatory bowel disease (IBD). This study aimed to quantify the serum sHLA-G levels of pediatric patients with IBD and assess the association of serum sHLA-G with disease activity.Methods:We enrolled 24 pediatric IBD patients Crohn's disease (CD) and ulcerative colitis (UC), n = 12 each] and 24 healthy controls. Based on the disease activity index, five and seven of the CD patients had mild and moderate/severe disease, respectively, whereas six of the UC patients were in remission and six had mild disease. Serum was collected and sHLA-G levels were determined by enzyme-linked immunosorbent assay (ELISA).Results:Pediatric patients with CD had significantly higher sHLA-G levels compared with patients with UC and healthy controls. Notably, serum sHLA-G levels were significantly higher in patients with moderate/severe CD than in those with mild CD.Conclusions:Serum sHLA-G levels correlate with disease activity in pediatric patients with CD and are higher in CD patients than in UC patients. Thus, sHLA-G is a potential biomarker for disease activity in CD.

Analysis of gene expression profile microarray data in complex regional pain syndrome.

The aim of the present study was to predict key genes and proteins associated with complex regional pain syndrome (CRPS) using bioinformatics analysis. The gene expression profiling microarray data, GSE47603, which included peripheral blood samples from 4patients with CRPS and 5 healthy controls, was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in CRPS patients compared with healthy controls were identified using the GEO2R online tool. Functional enrichment analysis was then performed using The Database for Annotation Visualization and Integrated Discovery online tool. Protein‑protein interaction (PPI) network analysis was subsequently performed using Search Tool for the Retrieval of Interaction Genes database and analyzed with Cytoscape software. A total of 257 DEGs were identified, including 243 upregulated genes and 14 downregulated ones. Genes in the human leukocyte antigen (HLA) family were most significantly differentially expressed. Enrichment analysis demonstrated that signaling pathways, including immune response, cell motion, adhesion and angiogenesis were associated with CRPS. PPI network analysis revealed that key genes, including early region 1A binding protein p300 (EP300), CREB‑binding protein (CREBBP), signal transducer and activator of transcription (STAT)3, STAT5A and integrin α M were associated with CRPS. The results suggest that the immune response may therefore serve an important role in CRPS development. In addition, genes in the HLA family, such as HLA‑DQB1 and HLA‑DRB1, may present potential biomarkers for the diagnosis of CRPS. Furthermore, EP300, its paralog CREBBP, and the STAT family genes, STAT3 and STAT5 may be important in the development of CRPS.

Basic understanding of the HLA system in allogeneic hematopoietic cell transplantation

Human immune responses are principally characterized by the human leukocyte antigen (HLA) system, a diverse set of cell surface molecules encoded by the major histocompatibility complex gene cluster on the short arm of chromosome 6. Among various members of the HLA family, the best characterized are the classic highly polymorphic class I and class II molecules that are responsible for antigen presentation to T cells and regulation of NK cell functions. In allogeneic hematopoietic cell transplantation, sophisticated approaches to donor-recipient allele-level matching at 3 class I (HLA-A/B/C) and 3 class II (HLA-DRB1/DQB1/DPB1) loci have been proven to lower the risk of immunologic complications such as graft failure and graft-versus-host disease, and possibly to confer effective graft-versus-malignancy effects. Future areas of research include clarifying the role of relatively non-polymorphic non-classical HLA molecules (HLA-E/F/G, HLA-DM/DO) and polymorphic/non-polymorphic class I-related molecules (MICA, MICB, HFE, MR1, CD1, FcRn) in the immune regulation that follows hematopoietic cell transplantation.

Abnormal gene expression and gene fusion in lung adenocarcinoma with high-throughput RNA sequencing

To explore the universal law of the abnormal gene expression and the structural variation of genes related to lung adenocarcinoma, the gene expression profile of GSE37765 were downloaded from Gene Expression Omnibus database. The differentially expressed genes (DEGs) were analyzed with t-test and NOISeq tool, and the core DEGs were screened out by combining with another RNA-seq data containing totally 77 pairs of samples in 77 patients with lung adenocarcinoma. Moreover, the functional annotation of the core DEGs was performed by using the Database for Annotation Visualization and Integrated Discovery following selection of oncogene and tumor suppressor by combining with tumor suppressor genes and Cancer Genes database, and motif-finding of core DEGs was performed with motif-finding algorithm Seqpos. We also used Tophat-fusion tool to further explore the fusion genes. In total, 850 downregulated DEGs and 206 upregulated DEGs were screened out in lung adenocarcinoma tissues. Next, we selected 543 core DEGs, including 401 downregulated and 142 upregulated genes, and vasculature development (P=1.89E-06) was significantly enriched among downregulated core genes, as well as mitosis (P=6.26E-04) enriched among upregulated core genes. On the basis of the cellular localization analysis of core genes, wnt-1-induced secreted protein 1 (WISP1) and receptor (G protein-coupled) activity modifying protein 1 (RAMP1) identified mainly located in extracellular region and extracellular space. We also screened one oncogene, v-myb avian myeloblastosis viral oncogene homolog-like 2 (MYBL2). Moreover, transcription factor GATA2 was mined by motif-finding analysis. Finally, four fusion genes belonged to the human leukocyte antigen (HLA) family. WISP1, RAMP1, MYBL2 and GATA2 could be potential targets of treatment for lung adenocarcinoma and the fusion of HLA family genes might have important roles in lung adenocarcinoma.

Family history and the frequency of human leukocyte antigen (HLA-DR) in centenarians

There are a few reports that associate several loci of the human leukocyte antigen (HLA) with longevity, such as DR1 which is significantly frequent in the very old, especially in Okinawa centenarians. In contrast DR9 is decreased. This report investigates 87 healthy Okinawan centenarians and 148 healthy Okinawan controls examined since 1987 with HLA phenotyping and family history questionnaires. The mean age in centenarians was 101.6 years, and that of controls was 66.4. We inquired the age and the cause of death of the parents of the subjects. Subjects whose parent's deaths were by suicide, homicide, accident, war or due to war trauma, were excluded and only those resulting from illness or natural causes were included. The relation between age of death of parents and DR types were studied. Compared to controls, DR1 was significantly increased in the centenarians (p = 0.036, RR 4.239), and DR8 was decreased (p = 0.012, RR = 0.412). When the mean age of death of parents for each DR group and that of total was determined, the mean death age of those with DR9 was significantly lower than the mean of the total (p < 0.05). More over, when the frequency rate of the DR types were compared with the parents' death age, that of DR9 decreased as the age of death increased. It is suggested that some loci of HLA-DR relate to longevity and some genetic protection against immunorelated diseases contributes to long-lived lineage.

Human Leukocyte Antigen Haplotype Sharing in Siblings With Psoriasis

To the Editor. —In the August 1990 issue of theArchives, Suarez-Almazor and Russell 1 reported their human leukocyte antigen (HLA) studies on siblings with psoriasis. Their article, as well as the editorial in the same issue, states that there are no previous systematic studies on HLA in families with several psoriatic patients. 2 They thus ignore our HLA family studies on psoriasis that were published in 1976. 3 This is unfortunate because the results of Suarez-Almazor and Russell disagree with our results based on a larger number of sibling pairs. Suarez-Almazor and Russell analyzed 15 sibling pairs with psoriasis and found that 13 were HLA identical and two shared one HLA haplotype. In our study we showed the pedigrees of 14 families with multiple cases of psoriasis. 2 Altogether, 35 sibling pairs could be analyzed when all the possible combinations were included. Of these, 13 were HLA identical, 19 shared