The Anti-Cyclic Citrullinated Protein Antibody Repertoire and Lung Involvement in Rheumatoid Arthritis

Information

  • Research Project
  • 10252749
  • ApplicationId
    10252749
  • Core Project Number
    R21AR076553
  • Full Project Number
    5R21AR076553-02
  • Serial Number
    076553
  • FOA Number
    PA-19-053
  • Sub Project Id
  • Project Start Date
    9/4/2020 - 3 years ago
  • Project End Date
    8/31/2022 - a year ago
  • Program Officer Name
    WANG, YAN Z
  • Budget Start Date
    9/1/2021 - 2 years ago
  • Budget End Date
    8/31/2022 - a year ago
  • Fiscal Year
    2021
  • Support Year
    02
  • Suffix
  • Award Notice Date
    8/11/2021 - 2 years ago
Organizations

The Anti-Cyclic Citrullinated Protein Antibody Repertoire and Lung Involvement in Rheumatoid Arthritis

PROJECT SUMMARY/ABSTRACT Though pulmonary fibrosis (PF) is a common and morbid complication of rheumatoid arthritis (RA), little is known about who with RA is at risk for its development and what predicts progressive and lethal PF. Anti-cy- clic citrullinated protein antibodies (ACPA) are present in patients before the development of joint disease in RA and are also found in a subset of patients with usual interstitial pneumonia (UIP), the most common form of PF seen in RA and the one that carries a dismal prognosis. Mounting evidence suggests that the lungs play a key role in the formation of these ACPA and may be intimately involved in the pathogenesis of disease in a subset of patients with RA. The hypothesis of this project is that as patients evolve from pre-RA (i.e., serum or sputum autoimmunity without disease) to RA joint disease to progressive RA-UIP, there is an expansion of cit- rullinated protein targets that encompass both lung and joint specific proteins, and this repertoire can predict clinical phenotype. We will test our hypothesis by identifying 4 subgroups of patients: (1) Pre-RA, (2) UIP pre- RA, (3) RA no UIP and (4) RA-UIP. We will look at the differences in this ACPA repertoire between these co- horts, identify lung-specific ACPA targets that can predict the onset of UIP in RA and explore the relationship between these ACPA targets and progressive lung disease. This proposal helps further the mission of the Na- tional Institute of Arthritis and Musculoskeletal and Skin Diseases by proposing patient-relevant clinical re- search that tests a hypothesis on the etiology of a major co-morbidity of rheumatoid arthritis. This proposal will broaden our understanding of the relationship between RA and the lungs, uncover valuable clinically relevant biomarkers and provide caregivers with tools to predict disease onset and behavior in order to personalize treatment decisions. Long-term goals of this proposal include reducing the burden of disease, strengthening our ability to enrich cohorts for upcoming clinical trials and highlighting plausible disease pathways for future research.

IC Name
NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
  • Activity
    R21
  • Administering IC
    AR
  • Application Type
    5
  • Direct Cost Amount
    106700
  • Indirect Cost Amount
    67945
  • Total Cost
    174645
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    846
  • Ed Inst. Type
  • Funding ICs
    NIAMS:174645\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    LIRR
  • Study Section Name
    Lung Injury, Repair, and Remodeling Study Section
  • Organization Name
    NATIONAL JEWISH HEALTH
  • Organization Department
  • Organization DUNS
    076443019
  • Organization City
    DENVER
  • Organization State
    CO
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    802062761
  • Organization District
    UNITED STATES