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Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary
Vivek Thakkar1,2,3,4,5,6, Karen A Patterson7,8, Wendy Stevens5
1Department of Rheumatology, Liverpool Hospital, Liverpool BC, NSW, 2170, Australia.
Insights
Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are not specific biomarkers for systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH). Elevated levels in SSc patients suggest a role in disease pathogenesis, regardless of pulmonary complications.
Area of Science:
- Rheumatology
- Pulmonology
- Immunology
Background:
- Systemic sclerosis (SSc) is a complex autoimmune disease with potential for severe organ involvement.
- Pulmonary arterial hypertension (PAH) is a serious complication of SSc, significantly impacting prognosis.
- Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are implicated in inflammatory and vascular processes.
Purpose of the Study:
- To investigate the utility of serum ICAM-1 and VCAM-1 as screening biomarkers for incident SSc-PAH.
- To compare ICAM-1 and VCAM-1 levels in SSc patients with and without PAH, and in control groups.
Main Methods:
- Cross-sectional study utilizing data from the Australian Scleroderma Cohort Study.
- Four participant groups: definite PAH (n=15), interstitial lung disease (ILD) (n=19), SSc-controls (n=30), and healthy controls (n=34).
- Serum levels of ICAM-1 and VCM-1 were quantified using a multiplex immunoassay.
Main Results:
- No significant differences in ICAM-1 or VCAM-1 levels were observed between the SSc-PAH group and the ILD, SSc-control, or healthy control groups.
- Systemic sclerosis patients exhibited significantly higher serum levels of both ICAM-1 and VCAM-1 compared to healthy controls (p < 0.0001 for both).
- Elevated levels of these adhesion molecules were present in SSc patients irrespective of pulmonary complications.
Conclusions:
- ICAM-1 and VCAM-1 are not specific biomarkers for screening SSc-PAH.
- The increased levels of ICAM-1 and VCAM-1 in SSc patients suggest a potential role in the underlying pathogenesis of systemic sclerosis itself.
- Further research is warranted to elucidate the precise role of these adhesion molecules in SSc.
Abstract:
Studies suggest elevated serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels may be markers of pulmonary arterial hypertension in systemic sclerosis (SSc-PAH). We sought to evaluate whether ICAM-1 and VCAM-1 levels are useful screening biomarkers for incident SSc-PAH. In this cross-sectional study, four groups were selected from the Australian Scleroderma Cohort Study: group 1 (n = 15) had definite PAH; group 2 (n = 19) had interstitial lung disease (ILD); group 3 (n = 30) were SSc-controls; and group 4 (n = 34) were healthy controls. Serum ICAM-1 and VCAM-1 levels were measured using the Millipore Milliplex MAP Human 2-Plex Panel. There were no differences in ICAM-1 levels in the PAH versus ILD group (263.0 ± 85.4 vs 380.4 ± 168.3 ng/mL, p = 0.136), SSc-controls (263.0 ± 85.4 vs 253.1 ± 98.0 ng/mL, p = 1.00), or healthy controls (263.0 ± 85.4 vs 201.8 ± 57.2 ng/mL, p = 0.093). Similarly, there were no differences in VCAM-1 level in PAH versus ILD groups (1476.2 ± 434.9 vs 1424.8 ± 527.6 ng/mL, p = 1.00) and SSc-controls (1476.2 ± 434.9 vs 1409.5 ± 341.1 ng/mL, p = 1.00). SSc subjects had significantly higher levels of ICAM-1 (297.4 ± 134.0 vs 201.8 ± 57.2 ng/mL, p < 0.0001) and VCAM-1 compared to healthy controls (1432.7 ± 427.4 vs 1125.6 ± 273.4 ng/mL, p < 0.0001). Neither ICAM-1 nor VCAM-1 is a specific screening biomarker of SSc-PAH. Instead, increased levels of these adhesion molecules in SSc, irrespective of pulmonary complications, suggest that they may play a role in SSc pathogenesis.
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