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Plasma levels of multiple cardiovascular- and inflammation-related proteins analysed for associations with disease activity and anti-cyclic citrullinated peptide status in active early rheumatoid arthritis


1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13

 

  1. Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital; Diagnostic Center, Silkeborg Regional Hospital, Silkeborg; Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, and Department of Rheumatology, Institute of Clinical Medicine, University of Aarhus and Aarhus University Hospital, Aarhus, Denmark. dzenanmasic@gmail.com
  2. Department of Rheumatology, Institute of Clinical Medicine, University of Aarhus and Aarhus University Hospital, Aarhus, Denmark.
  3. Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
  4. Danish Hospital for Rheumatic Diseases, Sønderborg, and University of Southern Denmark, Odense, Denmark.
  5. Copenhagen Center for Arthritis Research and DANBIO, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark.
  6. Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.
  7. Copenhagen Center for Arthritis Research and DANBIO, Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark.
  8. Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
  9. BioXpedia A/S, Aarhus, Denmark.
  10. Department of Mathematics and Computer Science (IMADA), University of Southern Denmark, Odense, Denmark.
  11. Department of Mathematics and Computer Science (IMADA), University of Southern Denmark, Odense, Denmark.
  12. Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, and Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
  13. Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, and Diagnostic Center, Silkeborg Regional Hospital, Silkeborg, Denmark.

CER16250
2023 Vol.41, N°9
PI 1801, PF 1807
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PMID: 36995323 [PubMed]

Received: 01/10/2022
Accepted : 02/01/2023
In Press: 16/03/2023
Published: 17/08/2023

Abstract

OBJECTIVES:
To compare plasma levels of 92 cardiovascular- and inflammation-related proteins (CIRPs) and to analyse for associations with anti-cyclic citrullinated peptide (anti-CCP) status and disease activity in early and treatment-naive rheumatoid arthritis (RA).
METHODS:
Olink CVD-III-panel was used to measure 92 CIRP plasma levels in 180 early, treatment-naive, and highly inflamed RA patients from the OPERA trial. CIRP plasma levels as well as correlation between CIRP plasma levels and RA disease activity were compared between anti-CCP groups. CIRP level-based hierarchical cluster analysis was performed in each anti-CCP group separately.
RESULTS:
The study included 117 anti-CCP-positive and 63 anti-CCP-negative RA patients. Among the 92 CIRPs measured, the levels of chitotriosidase-1 (CHIT1) and tyrosine-protein-phosphatase non-receptor-type substrate-1 (SHPS-1) were increased and those of metalloproteinase inhibitor-4 (TIMP-4) decreased in the anti-CCP-negative group compared to anti-CCP-positive group. The strongest associations with RA disease activity were found for interleukin-2 receptor-subunit-alpha (IL2-RA) and E-selectin levels in the anti-CCP-negative group and for C-C-motif chemokine-16 levels (CCL16) in the anti-CCP-positive group. None of the differences passed the Hochberg sequential multiplicity test, however, the CIPRs were interacting and thus the prerequisites of the Hochberg procedure were not fulfilled. CIRP level-based cluster analysis identified two patient clusters in both anti-CCP groups. Demographic and clinical characteristics were similar in the two clusters for each anti-CCP group.
CONCLUSIONS:
In active and early RA, the findings regarding CHIT1, SHPS-1 TIMP-4, IL2-RA, E-selectin, and CCL16 differed between the two anti-CCP groups. In addition, we identified two patient clusters that were independent of the anti-CCP status.

DOI: https://doi.org/10.55563/clinexprheumatol/hrjqdm

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