A systematic review and meta-analysis of circulating adhesion molecules in rheumatoid arthritis

Background: The availability of robust biomarkers of endothelial activation might enhance the identification of subclinical atherosclerosis in rheumatoid arthritis (RA). We investigated this issue by conducting a systematic review and meta-analysis of cell adhesion molecules in RA patients. Methods: We searched electronic databases from inception to 31 July 2023 for case-control studies assessing the circulating concentrations of immunoglobulin-like adhesion molecules (vascular cell, VCAM-1, intercellular, ICAM-1, and platelet endothelial cell, PECAM-1, adhesion molecule-1) and selectins (E, L, and P selectin) in RA patients and healthy controls. Risk of bias and certainty of evidence were assessed using the JBI checklist and GRADE, respectively. Results: In 39 studies, compared to controls, RA patients had significantly higher concentrations of ICAM-1 (standard mean difference, SMD = 0.81, 95% CI 0.62-1.00, p < 0.001; I2 = 83.0%, p < 0.001), VCAM-1 (SMD = 1.17, 95% CI 0.73-1.61, p < 0.001; I2 = 95.8%, p < 0.001), PECAM-1 (SMD = 0.82, 95% CI 0.57-1.08, p < 0.001; I2 = 0.0%, p = 0.90), E-selectin (SMD = 0.64, 95% CI 0.42-0.86, p < 0.001; I2 = 75.0%, p < 0.001), and P-selectin (SMD = 1.06, 95% CI 0.50-1.60, p < 0.001; I2 = 84.8%, p < 0.001), but not L-selectin. In meta-regression and subgroup analysis, significant associations were observed between the effect size and use of glucocorticoids (ICAM-1), erythrocyte sedimentation rate (VCAM-1), study continent (VCAM-1, E-selectin, and P-selectin), and matrix assessed (P-selectin). Conclusions: The results of our study support a significant role of cell adhesion molecules in mediating the interplay between RA and atherosclerosis. Further studies are warranted to determine whether the routine use of these biomarkers can facilitate the detection and management of early atherosclerosis in this patient group. PROSPERO Registration Number: CRD42023466662.