Increased adhesion molecule levels in systemic lupus erythematosus: relationships with severity of illness, autoimmunity, metabolic syndrome and cortisol levels

Abstract

Background This study was performed to assess adhesion molecules in systemic lupus erythematosus (SLE). Methods This case-control study examined 126 SLE patients and 48 healthy individuals. Blood levels of six adhesion molecules, cortisol, nuclear autoantibody (ANA) and anti-double stranded DNA (anti-dsDNA) titers were measured, while disease activity was assessed using the SLE Disease Activity Index (SLEDAI) score. Results Platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, P-selectin, and plasminogen activator inhibitor type-1 (PAI-1) were significantly higher in SLE patients than in controls. Binary logistic regression analysis showed that PECAM-1 and PAI-1 predicted SLE with a sensitivity of 86.5% and a specificity of 81.3%. ANA titers were significantly and positively associated with PECAM-1, VCAM-1, E-selectin, and PAI-1, whereas there were no associations between anti-dsDNA titers and adhesion molecules. Cortisol was negatively associated with PCAM-1 and ICAM-1. There were significant associations between metabolic syndrome (MetS) and E-selectin and PAI-1. 14.8% of the variance in the SLEDAI score was explained by the regression on PECAM-1 and MetS. Conclusions Our data show that adhesion molecules, especially PECAM-1, are significantly associated with SLE and disease activity, suggesting that they play a role in SLE pathophysiology. While MetS, ANA titers and cortisol levels modulate adhesion molecule levels, these associations do not explain the increased levels of adhesion molecules in SLE. Increased levels of adhesion molecules are new drug targets in SLE.

Comprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities

“…E-Selectin mediates immune cell adhesion, allowing neutrophils to adhere to vascular endothelial cells. E-selectin has been implicated in several cancers [44][45][46] , and as a potential biomarker for SLE and LN [47][48][49] . In this study, while sE-Selectin emerged as the most discriminatory urinary marker within Caucasian LN patients, it was not promising within the African-American cohort.…”

Relationship between serum vascular cell adhesion molecule-1 and endothelin-1 levels with organ involvement and disease activity in systemic lupus erythematosus patients

“…According to our study, serum sVCAM-1 and ET-1 levels were significantly higher in SLE patients compared to healthy controls, which was similar to previous studies. 18,22,41–51 Moreover, it was indicated that urinary VCAM-1 was elevated in patients with active SLE or lupus nephritis. 52–54 sVCAM-1 could be derived from numerous sources other than activated endothelium including bone marrow stromal cells, lymphatic endothelium and activated dendritic cells.…”

<p>Association of Plasminogen Activator Inhibitor 1 (PAI-1) 4G/5G Polymorphism and Susceptibility to SLE in Egyptian Children and Adolescents: A Multicenter Study</p>

“…These findings confirm and extend the results of previous studies in Turkish, Indian and Brazilian cohorts with adult-onset SLE. [37][38][39] In this study, we speculate that the PAI-1 4G/5G SNP may alter PAI-1 expression level as we observed that the 5G to 4G switch at −675 position was associated with increased PAI-1 serum concentrations among studied subjects and the PAI-1 5G/5G, 5G/4G, and 4G/4G genotypes were associated with low, intermediate, and high PAI-1 serum levels, respectively. Consistent with these findings, previous studies have explained that the deletion of the PAI 4G allele (only 4 guanine bases) has been associated with the inability to bind a repressor protein that decreases binding of the transcriptional activator, resulting in up to 6 times more PAI-1 mRNA expression and increased circulating PAI-1 levels.…”