Abstract
Objective 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. Conclusion 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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Clinical and Experimental Rheumatology |
| Vol/bind | 41 |
| Udgave nummer | 9 |
| Sider (fra-til) | 1801-1807 |
| Antal sider | 7 |
| ISSN | 0392-856X |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:Funding: this study was supported by grants from the Danish Rheumatism Association, Region of Southern Denmark, the University of Southern Denmark, and the Parker Institute. The investigator-initiated OPERA study was supported by grants from the Danish Rheumatism Association, Aarhus University and Abbott Laboratories, Denmark, who also provided free study medication (adalimumab and placebo-adalimumab). Triamcinolone was supplied by Meda Pharmaceuticals, Denmark. Abbott and Meda were not involved in the study set-up, data collection, analysis, or interpretation, and had no influence on the publication of data. The Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital is supported by a core grant from the Oak Foundation (OCAY-18-774-OFIL). No benefits from commercial sources were obtained. M. Kruhøffer is CEO at BioXpedia laboratory, where the protein analyses were carried out. Competing interests: none declared.
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