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

Dženan Mašić, Kristian Stengaard-Pedersen, Brian Bridal Løgstrup, Kim Hørslev-Petersen, Merete Lund Hetland, Peter Junker, Mikkel Østergaard, Claus Henrik Nielsen, Mogens Kruhøffer, Mathias Emil Bøgebjerg, Richard Röttger, Robin Christensen, Torkell Ellingsen

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.

Original languageEnglish
JournalClinical and Experimental Rheumatology
Volume41
Issue number9
Pages (from-to)1801-1807
Number of pages7
ISSN0392-856X
DOIs
Publication statusPublished - Sept 2023

Keywords

  • Anti-Citrullinated Protein Antibodies
  • Arthritis, Rheumatoid/diagnosis
  • Autoantibodies
  • E-Selectin
  • Humans
  • Inflammation
  • Interleukin-2
  • Peptides, Cyclic

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