Autoantibody Epitope Spreading in the Pre-Clinical Phase Predicts Progression to Rheumatoid Arthritis
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: William Robinson
PROVIDER: E-GEOD-32021 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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: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.
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Project description:Certain mouse strains have the ability to heal both ear wounds and knee articular cartilage injuries. A positive genetic correlation between cartilage healing and protection from osteoarthritis exists, which suggests that a common core of genes may operate in healing process. Here, we analyzed knee joint tissues from healer and non-healer mice and found that four genes were common to both ear wound and knee cartilage healing. Specific sequence differences between haler and non-healer parental strains were identified as potential causal polymorphisms. We suggest a common molecular and genetic basis of tissue healing. We collected tissue lysates from the formalin-fixed paraffin-embedded sections from mouse knee joints and analyzed the expression of several genes by Affymetrix QunatiGene Plex assay. Please note that 8-9 replicates were performed per each sample. The averaged (across the replicate samples) data was provided for each sample record and non-averaged data (from each replicate) is provided as a Series supplementary file (*setI.txt contains data from Panel 321347 and *setII.txt from panel 321389).
2013-07-04 | E-GEOD-48505 | biostudies-arrayexpress
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2014-04-25 | E-GEOD-55815 | biostudies-arrayexpress
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