Cell adhesion molecules and plasminogen activator inhibitor type-1 (PAI-1) in patients with rheumatoid arthritis: influence of metabolic syndrome
Rheumatoid arthritis (RA) is a chronic inflammatory and systemic disease characterized by endothelial activation. The main objective of this study was to verify the profile of cell adhesion molecules (CAM) in RA patients, and the influence of metabolic syndrome (MetS) and drugs used in the treatment of RA in this profile. A second objective was to propose models of prediction of activity in RA using these biomarkers. A total of 115 healthy individuals and 144 RA patients were enrolled. Disease activity was determined by DAS28 (disease activity score 28) based on erythrocyte sedimentation rate (DAS28-ESR) or C-reactive protein (DAS28-CRP). Serum CAM and plasminogen activator inhibitor type-1 (PAI-1), anthropometric and immunological parameters were measured. Vascular cell adhesion molecule-1 (VCAM-1) was significantly decreased, and PAI-1 was significantly higher in RA patients as compared to controls. Binary logistic regression analysis showed that VCAM-1, CRP, and tumor necrosis factor-α (TNF-α) predicted RA with a sensitivity of 95.9% and a specificity of 89.5%. 42.9% of the variance in DAS28-ESR and 49.2% of the variance in DAS28-CRP are explained by increased PAI-1, TNF-α, body mass index (BMI) and decreased platelet endothelial cell adhesion molecule 1 (PECAM-1). Our data show that lower levels of VCAM-1 are associated with RA independently of MetS, while increased PAI-1 levels were associated with both RA and MetS and increased selectins (E-selectin and P-selectin) were exclusively associated with MetS and not with RA. A model to predict disease activity based on PECAM-1, PAI-1, TNF-α, age and BMI is proposed.
KeywordsRheumatoid arthritis Cell adhesion molecules Plasminogen activator inhibitor type-1 Metabolic syndrome Tumor necrosis factor-α
This study was supported by the National Council of Brazilian Research-CNPq and by Araucária Foundation from the state of Paraná. We thank the University Hospital of State University of Londrina and HUTec Foundation for technical and administrative supports.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
All the participants included in this study provided written informed consent.
- 6.Yang X, Chang Y, Wei W. Endothelial dysfunction and inflammation: immunity in rheumatoid arthritis. Mediators Inflamm. 2016;2016:1–9.Google Scholar
- 20.Gonzales-Gay MA, Garcia-Unzueta MT, De Matias JM, Gonzales-Juanatey C, Garcia-Porrua C, Sanchez-Andrade A, et al. Influence of anti-TNF-α infliximab therapy on adhesion molecules associated with atherogenesis in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2006;24(4):373–9.Google Scholar
- 24.Prevoo MLL, MA, Kuper HH, van Leeuwen MA, van de Putte LBA, van Riel PLCM. Modified disease activity scores that include twenty-eight-joint counts. Arthritis Rheum. 1995,38(1):44-48.Google Scholar
- 26.Fransen J, Welsing P, Keijzer RD, Riel PV. Disease activity scores using C-reactive protein: CRP may replace ESR in the assessment of RA disease activity. Ann Rheum Dis. 2004;62:151.Google Scholar
- 28.Benjamini Y, Hochberg Y, Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B. 1995;57(1):289–300.Google Scholar
- 43.Costa NT, Iriyoda TMV, Kallaur AP, Delongui F, Alfieri DF, Lozovoy MAB, et al. Influence of insulin resistance and TNF-α on the inflammatory process, oxidative stress, and disease activity in patients with rheumatoid arthritis. Oxid Med Cell Longev. 2016;2016(Das 28):1–9.Google Scholar
- 46.Ugur M, Yildirim K, Kiziltunc A, Erdal A, Karatay S, Senel K. Correlation between soluble intercellular adhesion molecule 1 level and extracellular superoxide dismutase activity in rheumatoid arthritis: a possible association with disease activity. Scand J Rheumatol. 2004;33(4):239–43.CrossRefGoogle Scholar
- 47.Klimiuk PA, Sierakowski S, Latosiewicz R, Cylwik JP, Cylwik B, Skowronski J, et al. Soluble adhesion molecules (ICAM-1, VCAM-1, and E-selectin) and vascular endothelial growth factor (VEGF) in patients with distinct variants of rheumatoid synovitis. Ann Rheum Dis. 2002;61(9):804–9.CrossRefGoogle Scholar
- 48.Klimek E, Skalska A, Kwaśny-Krochin B, Surdacki A, Sulicka J, Korkosz M, et al. Differential associations of inflammatory and endothelial biomarkers with disease activity in rheumatoid arthritis of short duration. Mediators Inflamm. 2014;2014.Google Scholar
- 51.Scavuzzi BM, Simão ANC, Iryioda TMV, et al. Increased lipid and protein oxidation and lowered antioxidant defenses in systemic lupus erythematosus are associated with severity of illness, autoimmunity, increased adhesion molecules and Th1 and Th17 immune shift. Immunol Res. 2018;66(1):158–71.CrossRefGoogle Scholar