Human cerebrospinal fluid autoantibody lipid microarray profiling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: William Robinson
PROVIDER: E-GEOD-37830 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Lipids comprise 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives. Administration of these lipids ameliorated experimental autoimmune encephalomyelitis by suppressing activation and inducing apoptosis of autoreactive T cells, effects mediated by the lipids' saturated fatty-acid side chains. Thus, phospholipids represent a natural anti-inflammatory class of compounds that have potential as novel therapeutics for MS. Fig. 1A. Lipid-array profiling of IgG+IgM antibody reactivity in cerebrospinal fluid (CSF) samples from MS patients (relapsing remitting MS; secondary progressive MS; primary progressive MS), healthy controls, and other neurological disease controls. Lipid hits with the lowest FDR (q=0.048) were clustered according to their reactivity profiles. 48 different lipids were custom-spotted in duplicate using the CAMAG Automatic TLC Sampler (ATS4) robot to spray 200 nl of 10 to 100 pmol of lipids onto PVDF membranes affixed to the surface of microscope slides. The slides were probed with cerebrospinal fluid (CSF) from 59 human patient samples. 60 slides total: 18 relapsing-remitting MS, 14 secondary-progressive MS, 1 primary-progressive MS, 21 other neurological disease, 5 healthy control, 1 secondary Ab alone (not included in this submission). CSF diluted 1/10. HRP-conjugated secondary Ab (goat anti-human IgM/IgG) diluted 1/8000. ECL for 3 minutes.
2012-05-08 | E-GEOD-37664 | biostudies-arrayexpress
Project description:Lipids comprise 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives. Administration of these lipids ameliorated experimental autoimmune encephalomyelitis by suppressing activation and inducing apoptosis of autoreactive T cells, effects mediated by the lipids' saturated fatty-acid side chains. Thus, phospholipids represent a natural anti-inflammatory class of compounds that have potential as novel therapeutics for MS. Fig. 2A. Mini-Array I: IgG antibody reactivity to various glycero-3-phosphocholine lipids in CSF samples from patients with relapsing remitting MS and from control patients with other neurological disease. Lipid hits with the lowest FDR (q=0.029) were clustered according to their reactivity profiles. 47 different lipids were custom-spotted in duplicate using the CAMAG Automatic TLC Sampler (ATS4) robot to spray 200 nl of 10 to 100 pmol of lipids onto PVDF membranes affixed to the surface of microscope slides. The slides were probed with cerebrospinal fluid (CSF) from 24 human patient samples. 25 slides total: 13 relapsing-remitting MS, 11 other neurological disease, and 1 secondary Ab alone (not included in this submission). CSF diluted 1/20. HRP-conjugated secondary Ab (goat anti-human IgM/IgG) diluted 1/175. ECL for 3 minutes.
2012-05-08 | E-GEOD-37670 | biostudies-arrayexpress
Project description:Lipids comprise 70% of the myelin sheath, and autoantibodies against lipids may contribute to the demyelination that characterizes multiple sclerosis (MS). We used lipid antigen microarrays and lipid mass spectrometry to identify bona fide lipid targets of the autoimmune response in MS brain and an animal model of MS to explore the role of the identified lipids in autoimmune demyelination. We found that autoantibodies in MS target a phosphate group in phosphatidylserine and oxidized phosphatidylcholine derivatives. Administration of these lipids ameliorated experimental autoimmune encephalomyelitis by suppressing activation and inducing apoptosis of autoreactive T cells, effects mediated by the lipids' saturated fatty-acid side chains. Thus, phospholipids represent a natural anti-inflammatory class of compounds that have potential as novel therapeutics for MS. Fig. 2C. Mini-Array II: IgG antibody reactivity to lipids constituting polar head-group and side-chain modifications of PGPC in CSF samples from relapsing remitting MS patients and other neurological disease controls. Lipid hits with the lowest FDR (q=0.016) were clustered according to their reactivity profiles. 19 different lipids were custom-spotted in duplicate using the CAMAG Automatic TLC Sampler (ATS4) robot to spray 200 nl of 10 to 100 pmol of lipids onto PVDF membranes affixed to the surface of microscope slides. The slides were probed with cerebrospinal fluid (CSF) from 26 human patient samples. 27 slides total: 12 relapsing-remitting MS, 13 other neurological disease, 1 healthy control (not included in this submission), and 1 secondary Ab alone (not included in this submission). CSF diluted 1/20. HRP-conjugated secondary Ab (donkey anti-human IgG) diluted 1/8000. ECL for 3 minutes.
2012-05-08 | E-GEOD-37826 | biostudies-arrayexpress
Project description:Splenocytes harvested from mice with FIA were cultured in vitro and stimulated with 0.01 mg/ml fibrinogen for 3 days. Enriched T cells were transferred into 6-week-old naïve SJL mice, which developed visible signs of arthritis within 2 weeks. Synovial array profiling of plasma from the arthritic recipient mice demonstrated autoreactive B cell responses against peptides representing native fibrinogen, and further spreading of the responses to target collagen type V, cartilage gp39, and citrullinated vimentin. Custom-spotted protein slides were with plasma samples from individual mice. Four slides were probed with plasma derived from naïve mice and five slides were probed with plasma derived from mice injected with FIA T cells.
2010-05-05 | E-GEOD-18025 | biostudies-arrayexpress
Project description:Synovial antigen arrays were probed with 1:150 dilutions of plasma derived from SJL mice immunized with fibrinogen emulsified in CFA or with CFA alone. Autoantibody binding was detected with a Cy3-conjugated goat-anti-mouse IgG/M secondary antibody. SAM was applied to identify antigens with statistically significant differences in array reactivity between FIA and CFA control plasma (q < 0.01) obtained from mice before boosting. The SAM hits were subjected to hierarchical cluster analysis and are displayed as a heatmap. Synovial array profiling of FIA plasma demonstrated autoreactive B-cell responses against peptides representing native fibrinogen, and B-cell epitope spreading resulting in additional targeting of citrullinated fibrinogen in the samples obtained before boosting. Custom-spotted protein slides were probed with plasma samples from individual mice. Four slides were probed with plasma derived from mice immunized with CFA and six slides were probed with plasma derived from mice immunized with fibrinogen emulsified in CFA.
2010-05-05 | E-GEOD-18023 | biostudies-arrayexpress
Project description:Plasma collected from mice with FIA were pooled, and 0.3 ml was injected intravenously into 6-week-old naïve SJL mice on days 0 and 2. Synovial antigen array profiling of plasma from the arthritic recipient mice demonstrated autoreactive B-cell responses against peptides representing native fibrinogen and citrullinated fibrinogen, and further epitope spreading resulting in additional targeting of fibronectin, collagen type V, cartilage gp39, and clusterin. Custom-spotted protein slides were probed with plasma samples from individual mice. Four slides were probed with plasma derived from naïve mice and four slides were probed with plasma derived from mice injected with FIA plasma.
2010-05-05 | E-GEOD-18024 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE18023: Mice with FIA develop anti-native and anti-in vitro citrullinated fibrinogen antibodies GSE18024: FIA plasma induces arthritis in naïve mice GSE18025: Fibrinogen-reactive T cells transfer disease to naïve mice Refer to individual Series
2010-05-05 | E-GEOD-18073 | biostudies-arrayexpress
Project description:Many parasitic worms have a major adverse impact in human and animal populations worldwide due to the chronicity of their infections. There is a growing body of evidence indicating that extracellular vesicles (EVs) are intimately involved in modulating (suppressing) inflamma-tory/immune host responses and parasitism. As one of the most pathogenic nematodes of livestock animals, Haemonchus contortus is an ideal model system for EV exploration. Here, employing a multi-step enrichment process (in vitro culture, followed by ultracentrifugation, size exclusion and filtration), we enriched EVs from H. contortus and undertook the first comprehensive (qualitative and quantitative) multi-omic investigation of EV proteins and lipids using advanced liquid chro-matography–mass spectrometry and informatic methods. We identified and quantified 561 proteins and 446 lipids in EVs, and compared these molecules with those of adult worms. We identified unique molecules in EVs, such as proteins linked to lipid transportation and lipid species (i.e. glyc-erophospholipids and sphingolipids) associated with signalling, indicating an involvement of these molecules in parasite-host cross-talk. This work provides a solid starting point to explore the func-tional roles of EV-specific proteins and lipids in modulating parasite-host cross talk, and the pro-spect of finding ways of disrupting or interrupting this relationship to suppress or eliminate para-site infection.
2023-08-07 | PXD043320 | Pride
Project description:Lipids play a crucial role in signalling and metabolism, regulating the development and maintenance of the skeleton. Membrane lipids have been hypothesised to act as intermediates upstream of orphan phosphatase 1 (PHOSPHO1), a major contributor to phosphate generation required for bone mineralisation. Here, we spatially resolve the lipid atlas of the healthy mouse knee and demonstrate the effects of PHOSPHO1 ablation on the growth plate lipidome. Lipids spanning 17 subclasses were mapped across the knee joints of healthy juvenile and adult mice using matrix-assisted laser desorption ionisation imaging mass spectrometry (MALDI-IMS), with annotation supported by shotgun lipidomics. Multivariate analysis identified 96 and 80 lipid ions with differential abundances across joint tissues in juvenile and adult mice respectively. In both ages, marrow was enriched in phospholipid platelet activating factors (PAFs) and related metabolites, cortical bone had a low lipid content, while lysophospholipids were strikingly enriched in the growth plate, an active site of mineralisation and PHOSPHO1 activity. Spatially-resolved profiling of PHOSPHO1-knockout (KO) mice across the resting, proliferating, and hypertrophic growth plate zones revealed 272, 306, and 296 significantly upregulated, and 155, 220 and 190 significantly downregulated features, respectively, relative to wild type (WT) controls. Of note, phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, lysophosphatidylethanolamine and phosphatidylethanolamine derived lipid ions were upregulated in PHOSPHO1-KO versus WT. Our imaging pipeline has established a spatially-resolved lipid signature of joint tissues and has demonstrated that PHOSPHO1 ablation significantly alters the growth plate lipidome, highlighting an essential role of the PHOSPHO1-mediated membrane phospholipid metabolism in lipid and bone homeostasis.
2023-04-19 | PXD038909 | Pride
Project description:The microarray results showed that linalool sitimulation of lipid-loaded HepG2 cells rewired the hepatic transcriptome profile, with linalool being comparable to those of fenofibrate. Total of 8,988 genes that were commonly and significantly expressed in all experimental groups, including control hepatocytes, lipid-loaded hepatocytes, and lipid-loaded hepatocyted stimulated with linalool or fenofibrate, respectively, to compare the transcriptome profile of linalool (1mM) with those of hypotriglyceridemic drug, fenofibrate (100 ?M). Lipid loading of hepatocytes notably changed hepatic transcriptome profile, where 77 % of the selected genes showed >20% changes in expression (fold change > 1.2 or fold change <0.8). However, linalool stimulation of lipid-loaded cells showed that 48 % of the selected genes had expression changes of >20%. Thus, 29 % of the selected genes became to show less than 20% changes in expression after linalool stimulation compared to the lipid-loaded condition. Fenofibrate showed 46 % of the selected gene expression changes of >20%. Thus, 31 % of the seleted genes fell into the <20% change category compared to the lipid-loaded condition after fenofibrate stimulation. Untreated control vs. lipid-loaded HepG2 cells (3 biological replicates), untreated control vs. lipid-loaded HepG2 cells treated with fenofibrate (3 biological replicates), untreated control vs. lipid-loaded HepG2 cells treated with linalool (2 biological replicates). One replicate per array
2013-04-11 | E-GEOD-45961 | biostudies-arrayexpress