Search results for "leukocyte"
showing 10 items of 970 documents
Restriction fragment polymorphisms of the HLA-DR, HLA-DQ, and insulin gene regions in IDDM: The GAW5 data
1989
The primary aim of the insulin-dependent diabetes mellitus (IDDM) component of Genetic Analysis Workshop 5 (GAW5) was to collect and analyze new data on DNA polymorphisms closely linked to the HLA-D region and the insulin gene. The probes and restriction enzymes described here were used by all ten participating labs, and the data from Southern blotting were interpreted and reported according to conventions developed for the Workshop. These DNA data on members of 94 families with two or more IDDM sibs constitute the largest such sample available. The data were used in most of the analyses presented at the Workshop meeting, and are available on request.
HLA typing from RNA-Seq sequence reads.
2012
We present a method, seq2HLA, for obtaining an individual's human leukocyte antigen (HLA) class I and II type and expression using standard next generation sequencing RNA-Seq data. RNA-Seq reads are mapped against a reference database of HLA alleles, and HLA type, confidence score and locus-specific expression level are determined. We successfully applied seq2HLA to 50 individuals included in the HapMap project, yielding 100% specificity and 94% sensitivity at a P-value of 0.1 for two-digit HLA types. We determined HLA type and expression for previously un-typed Illumina Body Map tissues and a cohort of Korean patients with lung cancer. Because the algorithm uses standard RNA-Seq reads and …
Successful Replication of GWAS Hits for Multiple Sclerosis in 10,000 Germans Using the Exome Array
2015
Genome-wide association studies (GWAS) successfully identified various chromosomal regions to be associated with multiple sclerosis (MS). The primary aim of this study was to replicate reported associations from GWAS using an exome array in a large German study. German MS cases (n = 4,476) and German controls (n = 5,714) were genotyped using the Illumina HumanExome v1-Chip. Genotype calling was performed with the Illumina Genome Studio(TM) Genotyping Module, followed by zCall. Single-nucleotide polymorphisms (SNPs) in seven regions outside the human leukocyte antigen (HLA) region showed genome-wide significant associations with MS (P values < 5 × 10(-8) ). These associations have been repor…
Genetic analysis of IDDM: The GAW5 multiplex family dataset
1989
In a collaborative effort by 12 centers from Europe and North America, data were assembled from 94 multiplex families with insulin-dependent diabetes mellitus (IDDM) for analysis of genetic and other factors of possible etiological importance. The dataset contains information on the following genetic markers: HLA-DR beta and -DQ beta restriction fragment length polymorphisms (RFLPs), three RFLPs detected with two probes that map 5' to the insulin gene, the serologically defined HLA loci, and the immunoglobulin allotypes. Data also were included for auto-antibodies to insulin and pancreatic islet cells as possible indicators of pathogenesis and for antibodies to certain viruses that have bee…
Class II HLA interactions modulate genetic risk for multiple sclerosis
2015
Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and cla…
Genome search in celiac disease.
1998
SummaryCeliac disease (CD), a malabsorption disorder of the small intestine, results from ingestion of gluten. The HLA risk factors involved in CD are well known but do not explain the entire genetic susceptibility. To determine the localization of other genetic risk factors, a systematic screening of the genome has been undertaken. The typing information of 281 markers on 110 affected sib pairs and their parents was used to test linkage. Systematic linkage analysis was first performed on 39 pairs in which both sibs had a symptomatic form of CD. Replication of the regions of interest was then carried out on 71 pairs in which one sib had a symptomatic form and the other a silent form of CD. …
IκB kinase-driven nuclear factor-κB activation in patients with asthma and chronic obstructive pulmonary disease.
2011
Background Nuclear factor-κB (NF-κB) is a transcriptional factor of different inflammatory patterns involved in asthma and chronic obstructive pulmonary disease (COPD) that is tightly controlled by IκB kinase (IKK) complex. Objective We investigated the dysregulation of IKK-driven NF-κB activation in patients with asthma and COPD. Methods We assessed IKKα and IKKβ expression and activation, their regulation by glucocorticosteroids, and their involvement in IL-8 synthesis in PBMCs isolated from asthmatic patients, healthy smokers (HSs), patients with COPD, and control subjects. PBMCs from control subjects were stimulated with TNF-α and cigarette smoke extract in the presence or absence of fl…
Co-factors, Microbes, and Immunogenetics in Celiac Disease to Guide Novel Approaches for Diagnosis and Treatment.
2021
Celiac disease (CeD) is a frequent immune-mediated disease that affects not only the small intestine but also many extraintestinal sites. The role of gluten proteins as dietary triggers, HLA-DQ2 or -DQ8 as major necessary genetic predisposition, and tissue transglutaminase (TG2) as mechanistically involved autoantigen, are unique features of CeD. Recent research implicates many cofactors working in synergism with these key triggers, including the intestinal microbiota and their metabolites, nongluten dietary triggers, intestinal barrier defects, novel immune cell phenotypes, and mediators and cytokines. In addition, apart from HLA-DQ2 and -DQ8, multiple and complex predisposing genetic fact…
GM-CSF restores innate, but not adaptive, immune responses in glucocorticoid-immunosuppressed human blood in vitro.
2003
Abstract Infection remains the major complication of immunosuppressive therapy in organ transplantation. Therefore, reconstitution of the innate immunity against infections, without activation of the adaptive immune responses, to prevent graft rejection is a clinically desirable status in transplant recipients. We found that GM-CSF restored TNF mRNA and protein expression without inducing IL-2 production and T cell proliferation in glucocorticoid-immunosuppressed blood from either healthy donors or liver transplant patients. Gene array experiments indicated that GM-CSF selectively restored a variety of dexamethasone-suppressed, LPS-inducible genes relevant for innate immunity. A possible ex…
14th International HLA and Immunogenetics Workshop: Report on the Prospective Chronic Rejection Project
2007
An international collaborative study of 45 transplant centers was undertaken at the 14th International HLA (human leukocyte antigen) and Immunogenetics Workshop to see if HLA antibodies detected posttransplant are predictive of chronic graft failure. With the newly developed assay, MICA (major histocompatibility complex class I-related chain A) antibodies were also measured and their effect analyzed. Total of 5219 sera from patients who were more than 6 months posttransplant with functioning graft were tested for HLA antibodies by enzyme-linked immunosorbent assay, flow cytometry, or Luminex. HLA antibodies were found in 27.2% of kidney patients, 23.6% in the liver, 52.7% in the heart, and …