Full Papers
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
D. Mašić1, K. Stengaard-Pedersen2, B. Bridal Løgstrup3, K. Hørslev-Petersen4, M.L. Hetland5, P. Junker6, M. Østergaard7, C.H. Nielsen8, M. Kruhøffer9, M.E. Bøgebjerg10, R. Röttger11, R. Christensen12, T. Ellingsen13
- 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
- Department of Rheumatology, Institute of Clinical Medicine, University of Aarhus and Aarhus University Hospital, Aarhus, Denmark.
- Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
- Danish Hospital for Rheumatic Diseases, Sønderborg, and University of Southern Denmark, Odense, Denmark.
- 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.
- Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.
- 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.
- Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
- BioXpedia A/S, Aarhus, Denmark.
- Department of Mathematics and Computer Science (IMADA), University of Southern Denmark, Odense, Denmark.
- Department of Mathematics and Computer Science (IMADA), University of Southern Denmark, Odense, Denmark.
- 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.
- Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, and Diagnostic Center, Silkeborg Regional Hospital, Silkeborg, Denmark.
CER16250
Full Papers
PMID: 36995323 [PubMed]
Received: 01/10/2022
Accepted : 02/01/2023
In Press: 16/03/2023
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.
