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Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary manifestations

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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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Acknowledgements

The authors thank all members and contributors of the Australian Scleroderma Interest Group (ASIG). The authors thank the following people for assistance with sample preparation and data collection: Candice Rabusa, Sue Lester, Maureen Rischmueller, Alison Batty, Kerry Cooper, Kathleen Elford, Barbara Gemmell, Helen Marsden, Leah McWilliams. We thank the patients who participated in this study and St. Vincent’s Hospital Melbourne IT Department for their expert advice and continued support of the Australian Scleroderma Cohort Study and Database.

Funding

Financial support for the present study was provided by Scleroderma Australia, Arthritis Australia, Actelion Australia, Bayer, CSL Biotherapies, GlaxoSmithKline Australia and Pfizer. Dr. Nikpour holds a National Health and Medical Research Council (NHMRC) of Australia Career Development Fellowship (APP1126370).

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Correspondence to Mandana Nikpour.

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Vivek Thakkar has received honoraria for speaking from Actelion and has been on advisory boards for Actelion and GSK. The co-authors declare that they have no conflicts of interest.

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Thakkar, V., Patterson, K.A., Stevens, W. et al. Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary manifestations. Clin Rheumatol 37, 1563–1571 (2018). https://doi.org/10.1007/s10067-018-4081-7

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