Comprehensive Profiling of Rheumatoid Arthritis Antibody Repertoire
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE136052 | GEO | 2019/10/21
REPOSITORIES: GEO
Similar Datasets
Project description:Comprehensive Profiling of Rheumatoid Arthritis Antibody Repertoire
| PRJNA561136 | ENA
Project description:The presence or absence of autoantibodies against citrullinated proteins (ACPAs) distinguishes two main groups of rheumatoid arthritis (RA) patients with different etiology, prognosis, disease severity, and, presumably, disease pathogenesis. The heterogeneous responses of RA patients to various biologics, even among ACPA-positive patients, emphasize the need for further stratification of the patients. We use high-density protein array technology to evaluate ACPA reactivity. Identification of the proteome recognized by ACPAs may be a step to stratify RA patients according to immune reactivity. Methods: Pooled plasma samples from 10 anti-CCP negative and 15 anti-CCP positive RA patients were assessed for ACPA-content using a modified protein microarray containing 1,631 different natively folded proteins citrullinated in situ by protein arginine deiminases (PAD) 2 and PAD4. Results: IgG antibodies from anti-CCP positive RA plasma showed high-intensity binding to 87 proteins citrullinated by PAD2 and 99 proteins citrullinated by PAD4 without binding significantly to the corresponding native proteins. Curiously, the binding of IgG antibodies in anti-CCP-negative plasma was also enhanced by PAD2- and PAD4-mediated citrullination for 29 and 26 proteins, respectively. For only 4 proteins, significantly more ACPA-binding occurred after citrullination with PAD2 compared to citrullination with PAD4, while the opposite was true for 1 protein.
2022-01-05 | PXD024955 | Pride
Project description:Citrullinated and unmodified peptides (>95% purity, ProImmune AB) were immobilized onto a chemically modified glass slide, sera from RA patients and healthy controls were applied into the reactions sites and fluorescence intensity after incubation with anti-human IgG antibody was acquired in a laser scanner. Final results for each citrullinated peptide were calculated by subtracting the intensity values of corresponding arginine containing control peptide from citrullinated peptide for all RA patients and controls.
2015-10-25 | E-MTAB-3606 | 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.
2009-09-12 | GSE18024 | GEO
Project description:To examine the effects of GSK199 treatment on antibody responses, a synovial antigen array analysis was performed using day 35 sera derived from mice with CIA treated with 30 mg/kg qd, 30 mg/kg bid GSK199 or saline. The synovial antigen arrays contain nearly 200 peptides and proteins, both citrullinated and uncitrullinated, representing candidate antigens in RA. Significance Analysis of Microarrays identified 7 and 14 autoantibody reactivities that were statistically decreased in CIA mice treated with 30 mg/kg qd or 30 mg/kg bid GSK199 respectively, compared to PBS treatment. By comparison, over 150 native and citrullinated epitopes on the arrays did not exhibit significant differences in reactivity. Sera from mice treated with 30 mg/kg GSK199 qd exhibited decreased IgG reactivity to native epitopes such as peptides from human fibrinogen alpha and beta chains and keratin while sera from mice treated with 30 mg/kg bid GSK199 demonstrated decreased IgG reactivity to native epitopes including collagen IV, heat shock protein 65, peptides from human fibrinogen alpha and beta chains (two of which match those that were decreased in the 30 mg/kg qd group), and vimentin as compared to saline controls (q < 0.1%). Decreased autoantibody reactivity to citrullinated peptides from vimentin and fibromodulin were also observed in sera from mice treated with 30 mg/kg bid GSK199 compared to controls treated with saline (q < 0.1%), but not by GSK199 30 mg/kg qd. There were no differences between treatment with GSK199 or saline alone in the levels of autoantibodies to 38 other citrullinated proteins in the array. These data demonstrated that GSK199 treatment decreases the development of autoantibodies in CIA and impairs epitope spreading to a degree similar to that observed with pan-PAD inhibition.
2015-10-08 | GSE69680 | GEO
Project description:Cl-amidine treatment reduces autoantibody responses in CIA. Sera were collected from Cl-amidine and control treated mice, and autoantibodies in these samples were profiled using Synovial Antigen Arrays. Significance Analysis of Microarrays (SAM) was used to analyze the antigen array datasets, and identified 8 antigens with a significant difference in autoantibody reactivity (false discovery rate (q) < 5%). Hierarchical clustering was then performed to elucidate the relationships between the autoantibody profiles. The Cl-amidine treated mice clustered together and exhibited lower autoantibody titers against all of the 8 antigens identified by SAM, including autoantibody reactivity to native epitopes derived from cartilage as well as citrulline-modified filaggrin peptides.
2010-08-21 | GSE23731 | GEO
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:Malondialdehyde-modified epitopes (MDA-epitopes) can elicit specific autoantibody that expressed oxidative stress arising in rheumatoid arthritis (RA). The purpose of this study was to discover and validate MDA-peptide adducts as novel biomarkers using concanavalin A affinity chromatography, 1D SDS-PAGE, in-gel digestion, and label-free nano-LC-MS, and evaluate levels of serum MDA, MDA-protein adducts, proteins and autoantibody isotypes against an unmodified and MDA-peptide from Taiwanese female patients with RA and healthy controls (HCs). Levels of serum MDA and MDA-protein adducts were significantly higher in RA patients versus HCs. Four differentially expressed novel MDA-peptides were selected that relative modification ratio were 2-fold differences to examine protein levels and assess autoantibodies to MDA-peptides in RA patients compared with HCs. Four of peptides are autoantigens. Furthermore, 4 MDA-peptides can induce more autoantibody isotypes that are statistical significance in RA patients compared to HCs. Serum IgG and IgM against MDA-peptides showed excellent diagnostic performance in discriminating among RA patients and HCs: area under the curve (AUC, 0.96 ~ 0.98), sensitivity (88.9% ~ 97.8%) and specificity (88.9% ~ 100%). Autoantibodies to MDA-epitopes indicate oxidative modifications occurring in RA, and might be useful as clinical markers fro RA diagnosis if further investigated.
2021-02-25 | PXD004546 | Pride
Project description:BackgroundComputational biology contributes to a variety of areas related to life sciences and, due to the growing impact of translational medicine--the scientific approach to medicine in tight relation with basic science--, it is becoming an important player in clinical-related areas. In this study, we use computation methods in order to improve our understanding of the complex interactions that occur between molecules related to Rheumatoid Arthritis (RA).MethodologyDue to the complexity of the disease and the numerous molecular players involved, we devised a method to construct a systemic network of interactions of the processes ongoing in patients affected by RA. The network is based on high-throughput data, refined semi-automatically with carefully curated literature-based information. This global network has then been topologically analysed, as a whole and tissue-specifically, in order to translate the experimental molecular connections into topological motifs meaningful in the identification of tissue-specific markers and targets in the diagnosis, and possibly in the therapy, of RA.SignificanceWe find that some nodes in the network that prove to be topologically important, in particular AKT2, IL6, MAPK1 and TP53, are also known to be associated with drugs used for the treatment of RA. Importantly, based on topological consideration, we are also able to suggest CRKL as a novel potentially relevant molecule for the diagnosis or treatment of RA. This type of finding proves the potential of in silico analyses able to produce highly refined hypotheses, based on vast experimental data, to be tested further and more efficiently. As research on RA is ongoing, the present map is in fieri, despite being--at the moment--a reflection of the state of the art. For this reason we make the network freely available in the standardised and easily exportable .xml CellDesigner format at 'www.picb.ac.cn/ClinicalGenomicNTW/temp.html' and 'www.celldesigner.org'.
| S-EPMC2855702 | biostudies-literature
Project description:These assays represent antibody-binding assays to analyze seroprevalence of antigens and epitopes at the individual level and also to perform fine epitope mapping characterizations. In this screening 392,299 peptides derived from reactive (antigenic) regions of Trypanosoma cruzi proteins were displayed in the form of short peptides (tiling array, overlapped) and assayed with individual serum samples (antibodies) from Chagas Disease patients across the Americas. Sectorized peptide arrays (QX12-plex slides, Roche Nimblegen) were incubated with serum samples (primary antibodies), washed, and then incubated with a fluorescently-labeled anti-human IgG commercial antibody (secondary antibodies). Raw readouts of fluoresence (signal), as well as normalized signal values are provided in this submission for all samples analyzed. All samples were analyzed in duplicate (r1 = replicate 1; r2 = replicate 2).
2022-08-20 | E-MTAB-11655 | biostudies-arrayexpress