Single-cell transcriptomics in patients with anti-citrullinated peptide antibody-positive early rheumatoid arthritis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE260796 | GEO | 2025/01/13
REPOSITORIES: GEO
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Project description:Antigen-specific regulation of autoimmune disease is a major clinical research goal. In seropositive rheumatoid arthritis (RA), T cells help to autoreactive B cells matures the citrullinated antigen-specific immune response, generating RA-specific V-domain glycosylated anti-citrullinated (Cit) protein antibodies (VDG ACPA) before arthritis onset. Repeated low or escalating antigen doses administered under “sub-immunogenic” conditions generally favors tolerance. The aims of this study were to explore the safety, pharmacokinetics, immunological and clinical effects of s.c. DEN-181, comprising liposomes encapsulating self-peptide collagen II259-273 (CII) and NF-KB inhibitor 1,25-dihydroxycholecalciferol (calcitriol)
2022-12-05 | GSE208161 | GEO
Project description:Rheumatoid arthritis is a prototypical autoimmune arthritis affecting nearly 1% of the world population and is a significant cause of worldwide disability. Though prior studies have demonstrated the appearance of RA-related autoantibodies years before the onset of clinical RA, the pattern of immunologic events preceding the development of RA remains unclear. To characterize the evolution of the autoantibody response in the preclinical phase of RA, we used a novel multiplex autoantigen array to evaluate development of the anti-citrullinated protein antibodies (ACPA) and to determine if epitope spread correlates with rise in serum cytokines and imminent onset of clinical RA. To do so, we utilized a cohort of 81 patients with clinical RA for whom stored serum was available from 1-12 years prior to disease onset. We evaluated the accumulation of ACPA subtypes over time and correlated this accumulation with elevations in serum cytokines. We then used logistic regression to identify a profile of biomarkers which predicts the imminent onset of clinical RA (defined as within 2 years of testing). We observed a time-dependent expansion of ACPA specificity with the number of ACPA subtypes. At the earliest timepoints, we found autoantibodies targeting several innate immune ligands including citrullinated histones, fibrinogen, and biglycan, thus providing insights into the earliest autoantigen targets and potential mechanisms underlying the onset and development of autoimmunity in RA. Additionally, expansion of the ACPA response strongly predicted elevations in many inflammatory cytokines including TNF-α, IL-6, IL-12p70, and IFN-γ. Thus, we observe that the preclinical phase of RA is characterized by an accumulation of multiple autoantibody specificities reflecting the process of epitope spread. Epitope expansion is closely correlated with the appearance of preclinical inflammation, and we identify a biomarker profile including autoantibodies and cytokines which predicts the imminent onset of clinical arthritis. A total of 559 human sera were profiled using a custom made panel of putative rheumatoid arthritis associated autoantigens. The cohort was comprised of 79 patients with clinical RA for whom stored serum was available from 1-10 years prior to disease onset and 80 control subjects without RA that were matched to cases based on age, gender, race, region of assignment, and time of serum sampling.
2011-09-09 | E-GEOD-32016 | biostudies-arrayexpress
Project description:Transcriptional profiling of human synovial tissue from thirteen individuals with arthralgia who were IgM rheumatoid factor (RF) and/or anti-citrullinated protein antibody (ACPA) positive and without any evidence of arthritis. Survival analysis was used to identify transcripts associated with arthritis after follow up. This study was performed to investigate the molecular changes in synovium preceding arthritis development in at risk individuals.
2022-09-01 | E-MTAB-11874 | biostudies-arrayexpress
Project description:Rheumatoid arthritis is a prototypical autoimmune arthritis affecting nearly 1% of the world population and is a significant cause of worldwide disability. Though prior studies have demonstrated the appearance of RA-related autoantibodies years before the onset of clinical RA, the pattern of immunologic events preceding the development of RA remains unclear. To characterize the evolution of the autoantibody response in the preclinical phase of RA, we used a novel multiplex autoantigen array to evaluate development of the anti-citrullinated protein antibodies (ACPA) and to determine if epitope spread correlates with rise in serum cytokines and imminent onset of clinical RA. To do so, we utilized a cohort of 81 patients with clinical RA for whom stored serum was available from 1-12 years prior to disease onset. We evaluated the accumulation of ACPA subtypes over time and correlated this accumulation with elevations in serum cytokines. We then used logistic regression to identify a profile of biomarkers which predicts the imminent onset of clinical RA (defined as within 2 years of testing). We observed a time-dependent expansion of ACPA specificity with the number of ACPA subtypes. At the earliest timepoints, we found autoantibodies targeting several innate immune ligands including citrullinated histones, fibrinogen, and biglycan, thus providing insights into the earliest autoantigen targets and potential mechanisms underlying the onset and development of autoimmunity in RA. Additionally, expansion of the ACPA response strongly predicted elevations in many inflammatory cytokines including TNF-α, IL-6, IL-12p70, and IFN-γ. Thus, we observe that the preclinical phase of RA is characterized by an accumulation of multiple autoantibody specificities reflecting the process of epitope spread. Epitope expansion is closely correlated with the appearance of preclinical inflammation, and we identify a biomarker profile including autoantibodies and cytokines which predicts the imminent onset of clinical arthritis.
2011-09-10 | GSE32016 | GEO
Project description:Rheumatoid arthritis is a prototypical autoimmune arthritis affecting nearly 1% of the world population and is a significant cause of worldwide disability. Though prior studies have demonstrated the appearance of RA-related autoantibodies years before the onset of clinical RA, the pattern of immunologic events preceding the development of RA remains unclear. To characterize the evolution of the autoantibody response in the preclinical phase of RA, we used a novel multiplex autoantigen array to evaluate development of the anti-citrullinated protein antibodies (ACPA) and to determine if epitope spread correlates with rise in serum cytokines and imminent onset of clinical RA. To do so, we utilized a cohort of 81 patients with clinical RA for whom stored serum was available from 1-12 years prior to disease onset. We evaluated the accumulation of ACPA subtypes over time and correlated this accumulation with elevations in serum cytokines. We then used logistic regression to identify a profile of biomarkers which predicts the imminent onset of clinical RA (defined as within 2 years of testing). We observed a time-dependent expansion of ACPA specificity with the number of ACPA subtypes. At the earliest timepoints, we found autoantibodies targeting several innate immune ligands including citrullinated histones, fibrinogen, and biglycan, thus providing insights into the earliest autoantigen targets and potential mechanisms underlying the onset and development of autoimmunity in RA. Additionally, expansion of the ACPA response strongly predicted elevations in many inflammatory cytokines including TNF-?, IL-6, IL-12p70, and IFN-?. Thus, we observe that the preclinical phase of RA is characterized by an accumulation of multiple autoantibody specificities reflecting the process of epitope spread. Epitope expansion is closely correlated with the appearance of preclinical inflammation, and we identify a biomarker profile including autoantibodies and cytokines which predicts the imminent onset of clinical arthritis. A total of 556 human sera were profiled using multiplex cytokine and chemokine assays. The cohort was comprised of 80 patients with clinical RA for whom stored serum was available from 1-10 years prior to disease onset and 78 control subjects without RA matched to cases based on age, gender, race, region of assignment, and time of serum sampling.
2011-09-09 | E-GEOD-32019 | biostudies-arrayexpress
Project description:single-cell transcriptomics in patients with anti-citrullinated peptide antibody-positive early rheumatoid arthritis
| PRJNA1083512 | ENA
Project description:Rheumatoid arthritis is a prototypical autoimmune arthritis affecting nearly 1% of the world population and is a significant cause of worldwide disability. Though prior studies have demonstrated the appearance of RA-related autoantibodies years before the onset of clinical RA, the pattern of immunologic events preceding the development of RA remains unclear. To characterize the evolution of the autoantibody response in the preclinical phase of RA, we used a novel multiplex autoantigen array to evaluate development of the anti-citrullinated protein antibodies (ACPA) and to determine if epitope spread correlates with rise in serum cytokines and imminent onset of clinical RA. To do so, we utilized a cohort of 81 patients with clinical RA for whom stored serum was available from 1-12 years prior to disease onset. We evaluated the accumulation of ACPA subtypes over time and correlated this accumulation with elevations in serum cytokines. We then used logistic regression to identify a profile of biomarkers which predicts the imminent onset of clinical RA (defined as within 2 years of testing). We observed a time-dependent expansion of ACPA specificity with the number of ACPA subtypes. At the earliest timepoints, we found autoantibodies targeting several innate immune ligands including citrullinated histones, fibrinogen, and biglycan, thus providing insights into the earliest autoantigen targets and potential mechanisms underlying the onset and development of autoimmunity in RA. Additionally, expansion of the ACPA response strongly predicted elevations in many inflammatory cytokines including TNF-α, IL-6, IL-12p70, and IFN-γ. Thus, we observe that the preclinical phase of RA is characterized by an accumulation of multiple autoantibody specificities reflecting the process of epitope spread. Epitope expansion is closely correlated with the appearance of preclinical inflammation, and we identify a biomarker profile including autoantibodies and cytokines which predicts the imminent onset of clinical arthritis.
2011-09-10 | GSE32019 | GEO
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:Protein citrullination modification plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA), and anti-citrullinated protein antibodies (ACPAs) are extensively employed for clinical diagnosis of RA. However, there remains limited understanding regarding specific citrullinated proteins and their implications in the progression of RA. In this study, we screened and verified insulin-like growth factor-2 mRNA binding protein 1 (IGF2BP1) as a novel citrullinated protein and R167 was the primary citrullination site. Functional verification showed that citrullination at the R167 site of IGF2BP1 promoted the proliferation, migration and invasion of RA fibroblast-like synoviocytes (RA-FLSs). To further explore the specific downstream target of citrullinated IGF2BP1, RNA sequencing was conducted in this study.
2025-01-03 | GSE285602 | GEO
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