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Soluble adhesion molecules in pediatric rheumatic diseases
Bradley J Bloom1, Laurie C Miller, Peter R Blier
1Division of Pediatric Ambulatory Medicine, Hasbro Children's Hospital and Brown University Medical School, Providence, Rhode Island 02903, USA.
Insights
Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) may indicate active pediatric rheumatic diseases. Elevated E-selectin in vasculitis suggests endothelial activation, while L-selectin in lupus correlates with complement levels.
Area of Science:
- Pediatric Rheumatology
- Immunology
- Vascular Biology
Background:
- Adhesion molecules play a crucial role in leukocyte trafficking and immune responses.
- Understanding their role in pediatric rheumatic diseases is essential for disease management.
- Pediatric rheumatic diseases encompass a range of autoimmune and inflammatory conditions affecting children.
Purpose of the Study:
- To measure serum levels of specific adhesion molecules (ICAM-1, ICAM-3, VCAM-1, L-selectin, E-selectin) in children with various rheumatic diseases.
- To investigate the relationship between these adhesion molecule levels and clinical disease activity.
- To explore correlations with specific disease markers in systemic lupus erythematosus (SLE) and dermatomyositis (DM).
Main Methods:
- Retrospective analysis of banked sera from 18 children with rheumatic diseases (SLE, mixed connective tissue disease, DM, vasculitis).
- Quantification of soluble adhesion molecules using sandwich ELISA.
- Comparison of levels across diagnoses, between active and inactive disease states, and correlation with clinical and laboratory markers of disease activity.
Main Results:
- A trend towards higher soluble E-selectin (sE-selectin) levels was observed in vasculitis compared to other diagnoses.
- Soluble intercellular adhesion molecule-1 (sICAM-1) levels were significantly higher in patients with active disease across all diagnoses.
- L-selectin levels showed a significant positive correlation with C4 complement levels in SLE patients.
Conclusions:
- Elevated sE-selectin in vasculitis may indicate endothelial activation and vascular damage.
- L-selectin's correlation with C4 in SLE suggests a role in leukocyte adherence and immune complex deposition.
- sICAM-1 may serve as a general marker for active pediatric rheumatic diseases, though its sensitivity for routine clinical use requires further investigation.
Objective:
To determine serum levels of adhesion molecules ICAM-1, ICAM-3, VCAM-1, L-selectin, and E-selectin in children with a variety of pediatric rheumatic diseases and investigate their relationship to clinical disease activity.
Methods:
Retrospective review of records of 18 children with rheumatic diseases who had banked sera available for study. Eight children had systemic lupus erythematosus (SLE), 2 mixed connective tissue disease, 4 dermatomyositis (DM), and 4 various forms of vasculitis. Levels of the soluble adhesion molecules were determined by sandwich ELISA. Levels were compared among patients with the various diagnoses and between patients with active vs inactive disease. Levels were also correlated with erythrocyte sedimentation rate in all patients; C3, C4, and total hemolytic complements and anti-dsDNA antibodies in SLE; and creatine phosphokinase, aldolase, and von Willebrand factor (vWF) antigen levels in DM. Levels also correlated with disease activity scores, which varied by diagnosis.
Results:
A trend toward higher levels of sE-selectin was found in vasculitis vs other diagnoses (p = 0.08). sICAM-1 was higher in patients with active vs inactive disease (p = 0.05) across all diagnoses. L-selectin levels correlated with C4 complement levels in SLE patients (r = 0.76, p = 0.03), and there was a trend toward an inverse correlation between levels of sE-selectin and vWF (r = -0.93, p = 0.08). There was no direct correlation of the adhesion molecule levels with any of the disease activity scores.
Conclusion:
The small number of patients and retrospective design of this study mean that any results must be interpreted with caution. We conclude: (1) Elevated E-selectin levels in vasculitis likely reflect the high degree of endothelial activation and possibly overt vascular damage in those conditions. (2) The correlation of sL-selectin with C4 in SLE may indicate that downregulation of shedding of cell surface L-selectin is involved in continued adherence of leukocytes to endothelium, possibly causing further damage and immune complex deposition in this condition. (3) The trend toward inverse correlation between sE-selectin and vWF:Ag in DM is curious, but may show that the role of endothelium in the pathophysiology of this disease is different from those such as vasculitis. (4) Levels of sICAM- I may be a useful marker of active vs quiescent disease in general in the pediatric rheumatic diseases, although lack of correlation with disease activity indices may indicate that it is too insensitive to smaller differences in disease activity to be recommended for routine clinical use.