Browse
Submit Data
Databases
API
Help

Dataset Information

7 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

KIR2DS5 in the presence of HLA-C C2 protects against endometriosis.

ABSTRACT: Endometriosis is defined as the presence of functional endometrial tissue outside the uterine cavity. Several hypotheses have attempted to explain the etiology and pathogenesis of endometriosis. Recently, it has been suggested that a defect of the natural killer (NK) activity in the recognition and lysis of endometrial cells is one of the crucial points in the development of this disease. Natural killer cells can express killer immunoglobulin-like receptors (KIR), which recognize class I human leukocyte antigens on target cells. We asked whether polymorphisms in KIR, HLA-C, and HLA-B genes are risk factors for endometriosis. We tested 153 women with endometriosis diagnosed on the basis of laparoscopic and histological examination, and 213 control healthy women, who gave birth to at least one child. The frequency of KIR genes in patients was similar to that in controls except for KIR2DS5, which exerted a protective effect only in HLA-C C2-positive individuals. Moreover, KIR2DS5-positive women with endometriosis had 13 times lower chance that the disease would occupy the peritoneum than KIR2DS5- and KIR2DS4del-negative ones (OR = 0.077, P = 0.0061). Similarly, KIR2DS4del-positive endometriotic persons had 11 times lower chance for peritoneal disease (OR = 0.094, P < 0.001). Negative linkage disequilibrium between KIR2DS5 and KIR2DS4del indicates that these genes are mutually exclusive. Our data suggest that KIR2DS5 may be associated with protection from endometriosis, whereas KIR2DS4del seems to be associated with higher disease stages, possibly by exclusion of protective KIR2DS5.

SUBMITTER: Nowak I

PROVIDER: S-EPMC4357646 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2.

Project description:Many common disorders of pregnancy are attributed to insufficient invasion of the uterine lining by trophoblast, fetal cells that are the major cell type of the placenta. Interactions between fetal trophoblast and maternal uterine NK (uNK) cells--specifically interactions between HLA-C molecules expressed by the fetal trophoblast cells and killer Ig-like receptors (KIRs) on the maternal uNK cells--influence placentation in human pregnancy. Consistent with this, pregnancies are at increased risk of preeclampsia in mothers homozygous for KIR haplotype A (KIR AA). In this study, we have demonstrated that trophoblast expresses both paternally and maternally inherited HLA-C surface proteins and that maternal KIR AA frequencies are increased in affected pregnancies only when the fetus has more group 2 HLA-C genes (C2) than the mother. These data raise the possibility that there is a deleterious allogeneic effect stemming from paternal C2. We found that this effect also occurred in other pregnancy disorders (fetal growth restriction and recurrent miscarriage), indicating a role early in gestation for these receptor/ligand pairs in the pathogenesis of reproductive failure. Notably, pregnancy disorders were less frequent in mothers that possessed the telomeric end of the KIR B haplotype, which contains activating KIR2DS1. In addition, uNK cells expressed KIR2DS1, which bound specifically to C2+ trophoblast cells. These findings highlight the complexity and central importance of specific combinations of activating KIR and HLA-C in maternal-fetal immune interactions that determine reproductive success.

| S-EPMC2964995 | biostudies-literature

Phosphoinositide 3-Kinase-C2? Regulates Polycystin-2 Ciliary Entry and Protects against Kidney Cyst Formation.

Project description:Signaling from the primary cilium regulates kidney tubule development and cyst formation. However, the mechanism controlling targeting of ciliary components necessary for cilium morphogenesis and signaling is largely unknown. Here, we studied the function of class II phosphoinositide 3-kinase-C2? (PI3K-C2?) in renal tubule-derived inner medullary collecting duct 3 cells and show that PI3K-C2? resides at the recycling endosome compartment in proximity to the primary cilium base. In this subcellular location, PI3K-C2? controlled the activation of Rab8, a key mediator of cargo protein targeting to the primary cilium. Consistently, partial reduction of PI3K-C2? was sufficient to impair elongation of the cilium and the ciliary transport of polycystin-2, as well as to alter proliferation signals linked to polycystin activity. In agreement, heterozygous deletion of PI3K-C2? in mice induced cilium elongation defects in kidney tubules and predisposed animals to cyst development, either in genetic models of polycystin-1/2 reduction or in response to ischemia/reperfusion-induced renal damage. These results indicate that PI3K-C2? is required for the transport of ciliary components such as polycystin-2, and partial loss of this enzyme is sufficient to exacerbate the pathogenesis of cystic kidney disease.

| S-EPMC4814170 | biostudies-literature

A T cell epitope-based vaccine protects against chlamydial infection in HLA-DR4 transgenic mice.

Project description:Vaccination with recombinant chlamydial protease-like activity factor (rCPAF) has been shown to provide robust protection against genital Chlamydia infection. Adoptive transfer of IFN-? competent CPAF-specific CD4? T cells was sufficient to induce early resolution of chlamydial infection and reduction of subsequent pathology in recipient IFN-?-deficient mice indicating the importance of IFN-? secreting CD4? T cells in host defense against Chlamydia. In this study, we identify CD4? T cell reactive CPAF epitopes and characterize the activation of epitope-specific CD4? T cells following antigen immunization or Chlamydia challenge. Using the HLA-DR4 (HLA-DRB1*0401) transgenic mouse for screening overlapping peptides that induced T cell IFN-? production, we identified at least 5 CPAF T cell epitopes presented by the HLA-DR4 complex. Immunization of HLA-DR4 transgenic mice with a rCPAFep fusion protein containing these 5 epitopes induced a robust cell-mediated immune response and significantly accelerated the resolution of genital and pulmonary Chlamydia infection. rCPAFep vaccination induced CPAF-specific CD4? T cells in the spleen were detected using HLA-DR4/CPAF-epitope tetramers. Additionally, CPAF-specific CD4? clones could be detected in the mouse spleen following Chlamydia muridarum and a human Chlamydia trachomatis strain challenge using these novel tetramers. These results provide the first direct evidence that a novel CPAF epitope vaccine can provide protection and that HLA-DR4/CPAF-epitope tetramers can detect CPAF epitope-specific CD4? T cells in HLA-DR4 mice following C. muridarum or C. trachomatis infection. Such tetramers could be a useful tool for monitoring CD4? T cells in immunity to Chlamydia infection and in developing epitope-based human vaccines using the murine model.

| S-EPMC3843363 | biostudies-literature

TCR gene transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 epitopes as melanoma-specific immune targets.

Project description:Adoptive therapy with TCR gene-engineered T cells provides an attractive and feasible treatment option for cancer patients. Further development of TCR gene therapy requires the implementation of T-cell target epitopes that prevent "on-target" reactivity towards healthy tissues and at the same time direct a clinically effective response towards tumor tissues. Candidate epitopes that meet these criteria are MAGE-C2(336-344)/HLA-A2 (MC2/A2) and MAGE-A3(243-258)/HLA-DP4 (MA3/DP4). We molecularly characterized TCRαβ genes of an MC2/A2-specific CD8 and MA3/DP4-specific CD4 T-cell clone derived from melanoma patients who responded clinically to MAGE vaccination. We identified MC2/A2 and MA3/DP4-specific TCR-Vα3/Vβ28 and TCR-Vα38/Vβ2 chains and validated these TCRs in vitro upon gene transfer into primary human T cells. The MC2 and MA3 TCR were surface-expressed and mediated CD8 T-cell functions towards melanoma cell lines and CD4 T-cell functions towards dendritic cells, respectively. We intend to start testing these MAGE-specific TCRs in phase I clinical trial.

| S-EPMC3287115 | biostudies-literature

Maternal KIR in combination with paternal HLA-C2 regulate human birth weight.

Project description:Human birth weight is subject to stabilizing selection; babies born too small or too large are less likely to survive. Particular combinations of maternal/fetal immune system genes are associated with pregnancies where the babies are ≤ 5th birth weight centile, specifically an inhibitory maternal KIR AA genotype with a paternally derived fetal HLA-C2 ligand. We have now analyzed maternal KIR and fetal HLA-C combinations at the opposite end of the birth weight spectrum. Mother/baby pairs (n = 1316) were genotyped for maternal KIR as well as fetal and maternal HLA-C. Presence of a maternal-activating KIR2DS1 gene was associated with increased birth weight in linear or logistic regression analyses of all pregnancies >5th centile (p = 0.005, n = 1316). Effect of KIR2DS1 was most significant in pregnancies where its ligand, HLA-C2, was paternally but not maternally inherited by a fetus (p = 0.005, odds ratio = 2.65). Thus, maternal KIR are more frequently inhibitory with small babies but activating with big babies. At both extremes of birth weight, the KIR associations occur when their HLA-C2 ligand is paternally inherited by a fetus. We conclude that the two polymorphic immune gene systems, KIR and HLA-C, contribute to successful reproduction by maintaining birth weight between two extremes with a clear role for paternal HLA.

| S-EPMC4028203 | biostudies-literature

Crystal structure of HLA-DQ0602 that protects against type 1 diabetes and confers strong susceptibility to narcolepsy.

Project description:The MHC class II molecule DQ0602 confers strong susceptibility to narcolepsy but dominant protection against type 1 diabetes. The crystal structure of DQ0602 reveals the molecular features underlying these contrasting genetic properties. Structural comparisons to homologous DQ molecules with differential disease associations highlight a previously unrecognized interplay between the volume of the P6 pocket and the specificity of the P9 pocket, which implies that presentation of an expanded peptide repertoire is critical for dominant protection against type 1 diabetes. In narcolepsy, the volume of the P4 pocket appears central to the susceptibility, suggesting that the presentation of a specific peptide population plays a major role.

| S-EPMC357041 | biostudies-literature

DIDS protects against neuronal injury

Project description:Using long-oligo beadschip arrays, we examined the global gene expression profile in cultured hippocampal slices under the simulated ischemic condition with and without the presence of DIDS . Control-ACSF: cultured hippocampal slices were incubated with ACSF for 2 hours and were analysed on whole-genome expression chips to determine the gene expression profile. This group was used as controls for IS-treated groups and ACSF+DIDS-treated grous. IS: cultured hippocampal slices were treated wtih IS for 2 hours and the gene expression was analyzed and compared with the control group. IS+DIDS: cultured slices were treated with both IS and DIDS for 2 hours and the gene expression profile was determined. Differentially expression genes were identified by comparing with IS group. ACSF+DIDS: cultured slices were incubated with both ACSF and DIDS for 2 hours and gene expression profile was determined. This group was used as a control for IS+DIDS group. ACSF: artificial cerebral spinal fluid DIDS: 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid IS: ischemic solution

2010-05-15 | E-GEOD-12426 | biostudies-arrayexpress

Genetic variations in STAT4,C2,HLA-DRB1 and HLA-DQ associated with risk of hepatitis B virus-related liver cirrhosis.

Project description:Recent genome-wide associated studies (GWASs) have revealed several common loci associated with the risk of hepatitis B virus (HBV)- or hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). We selected 15 single nucleotide polymorphisms (SNPs) identified through GWASs on HBV- or HCV-related HCC, and genotyped them in two independent Chinese cohorts of chronic HBV carriers, including 712 LC cases and 2601 controls. The association of each SNP with the risk of HBV-related LC was assessed by meta-analysis of the two cohorts. Of the 12 SNPs reported in HBV-related HCC GWASs, five SNPs (rs7574865 in STAT4, rs9267673 near C2, rs2647073 and rs3997872 near HLA-DRB1 and rs9275319 near HLA-DQ), were found to be significantly associated with the risk of HBV-related LC (rs7574865: P?=?1.79?×?10(-2), OR?=?1.17, 95% CI?=?1.03-1.34; rs9267673: P?=?4.91?×?10(-4), OR?=?1.37, 95% CI?=?1.15-1.63; rs2647073: P?=?3.53?×?10(-5), OR?=?1.63, 95% CI?=?1.29-2.06; rs3997872: P?=?4.22?×?10(-4), OR?=?1.86, 95% CI?=?1.32-2.62; rs9275319: P?=?1.30?×?10(-2), OR?=?1.32, 95% CI?=?1.06-1.64). However, among the three SNPs associated with the risk of HCV-related HCC in previous GWASs, none of them showed significant association with the risk of HBV-related LC. Our results suggested that genetic variants associated with HBV-related hepatocarcinogenesis may already play an important role in the progression from CHB to LC.

| S-EPMC4633722 | biostudies-literature

Hypoxia‑induced lactate dehydrogenase A protects cells from apoptosis in endometriosis.

Project description:The pathological expression and function of lactate dehydrogenase A (LDHA), a key enzyme that converts pyruvate into lactic acid during glycolysis, remains unknown in endometriosis. In the present study, LDHA expression in tissue samples was determined by immunohistochemistry. To examine whether LDHA was induced by hypoxia, primary cultured endometrial stromal cells (ESCs) and glandular epithelial Ishikawa cells were exposed to 1% O2 (hypoxia) or 21% O2 (normoxia). Cellular functions were assessed by flow cytometry, Transwell and Cell Counting Kit‑8 assays in LDHA‑silenced ESCs and Ishikawa cells. Mitochondrial functions were evaluated using mitochondrial membrane potential JC‑1 staining, reactive oxygen species flow cytometric analysis and ATP detection. Additionally, lactic acid production was examined and western blotting was used to evaluate the expression levels of proteins associated with apoptosis, cell cycle and glycolysis, as well as regulatory proteins involved in epithelial‑mesenchymal transformation and glycolytic pathways. LDHA was localized to endometrial glandular cells and stromal cells. However, LDHA protein expression was higher in endometriotic lesions compared with that in normal and eutopic endometria. LDHA expression levels in ectopic glandular cells were higher during the proliferative stage compared with during the secretory stage. Hypoxia treatment of Ishikawa cells and ESCs markedly induced the mRNA and protein expression of LDHA. Silencing of LDHA expression in Ishikawa cells and THESC cells significantly promoted impaired mitochondrial function and apoptosis while inhibiting migration and glycolysis. However, it had no obvious effect on proliferation. In conclusion, the present study revealed that LDHA was highly expressed in endometriotic tissues, where it may serve a notable role in the occurrence and development of endometriosis.

| S-EPMC8281285 | biostudies-literature

OX40L protects against inflammation-driven fibrosis

Project description:Fibrosis is a leading cause of deaths in industrialized countries and has no effective therapy. We demonstrated that blockade of OX40L prevented inflammation-driven fibrosis affecting the skin and the lungs and promotes regression of established dermal fibrosis in different murine models. To characterize the pathways involved in the protection of skin fibrosis and affected by OX40L blocking, we used microarrays and identified distinct genes differentially expressed between ox40l+/+ and ox40l-/- in the bleomycin-induced dermal fibrosis mouse model. Total RNA were extracted from lesional skin samples of 3 ox40l+/+ and 4 ox40l-/- male mice aged 9 weeks treated with bleomycin for 3 weeks, and were hybridized on Affymetrix microarrays.

2016-08-09 | E-GEOD-73705 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data