Journal article
Multifaceted immune dysregulation characterizes individuals at-risk for rheumatoid arthritis
Nature communications, Vol.14(1), pp.7637-12
11/22/2023
DOI: 10.1038/s41467-023-43091-8
PMCID: PMC10665556
PMID: 37993439
Abstract
Molecular markers of autoimmunity, such as antibodies to citrullinated protein antigens (ACPA), are detectable prior to inflammatory arthritis (IA) in rheumatoid arthritis (RA) and may define a state that is 'at-risk' for future RA. Here we present a cross-sectional comparative analysis among three groups that include ACPA positive individuals without IA (At-Risk), ACPA negative individuals and individuals with early, ACPA positive clinical RA (Early RA). Differential methylation analysis among the groups identifies non-specific dysregulation in peripheral B, memory and naïve T cells in At-Risk participants, with more specific immunological pathway abnormalities in Early RA. Tetramer studies show increased abundance of T cells recognizing citrullinated (cit) epitopes in At-Risk participants, including expansion of T cells reactive to citrullinated cartilage intermediate layer protein I (cit-CILP); these T cells have Th1, Th17, and T stem cell memory-like phenotypes. Antibody-antigen array analyses show that antibodies targeting cit-clusterin, cit-fibrinogen and cit-histone H4 are elevated in At-Risk and Early RA participants, with the highest levels of antibodies detected in those with Early RA. These findings indicate that an ACPA positive at-risk state is associated with multifaceted immune dysregulation that may represent a potential opportunity for targeted intervention.
Details
- Title: Subtitle
- Multifaceted immune dysregulation characterizes individuals at-risk for rheumatoid arthritis
- Creators
- Eddie A James - Seattle UniversityV Michael Holers - University of Colorado Anschutz Medical CampusRadhika Iyer - VA Palo Alto Health Care SystemE Barton Prideaux - University of California San DiegoNavin L Rao - JanssenCliff Rims - Seattle UniversityVirginia S Muir - Seattle UniversitySylvia E Posso - Seattle UniversityMichelle S Bloom - VA Palo Alto Health Care SystemAmin Zia - VA Palo Alto Health Care SystemSerra E Elliott - VA Palo Alto Health Care SystemJulia Z Adamska - Stanford UniversityRizi Ai - University of California San DiegoR Camille Brewer - VA Palo Alto Health Care SystemJennifer A Seifert - University of Colorado Anschutz Medical CampusLauraKay Moss - University of Colorado Anschutz Medical CampusSaman Barzideh - University of Colorado Anschutz Medical CampusM Kristen Demoruelle - University of Colorado Anschutz Medical CampusChristopher C Striebich - University of Colorado Anschutz Medical CampusYuko Okamoto - University of Colorado Anschutz Medical CampusEnkhtsogt Sainbayar - University of Colorado Anschutz Medical CampusAlexandra A Crook - University of Colorado Anschutz Medical CampusRyan A Peterson - Colorado School of Public HealthLauren A Vanderlinden - University of Colorado Anschutz Medical CampusWei Wang - University of California San DiegoDavid L Boyle - University of California San DiegoWilliam H Robinson - Stanford UniversityJane H Buckner - Seattle UniversityGary S Firestein - University of California San DiegoKevin D Deane - University of Colorado Anschutz Medical Campus
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.14(1), pp.7637-12
- DOI
- 10.1038/s41467-023-43091-8
- PMID
- 37993439
- PMCID
- PMC10665556
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Grant note
- T32 AR064194 / NIAMS NIH HHS U01 AI101981 / NIAID NIH HHS R01 AR065466 / NIAMS NIH HHS
- Language
- English
- Date published
- 11/22/2023
- Academic Unit
- Biostatistics; Internal Medicine
- Record Identifier
- 9984914148402771
Metrics
4 Record Views