Background In recent studies the peripheral blood of SSc patients contained elevated levels of soluble inflammatory mediators such as endothelin-1 (ET-1), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)(1, 2). Nonetheless, these data were derived from small cohorts involving patients with variable disease duration and variable disease activity. Hypothetically, the inflammatory mechanisms that drive SSc are most active in early SSc. It is of interest to identify biomarkers of disease activity in these patients that may be used in future trials with anti-inflammatory agents. Therefore, we tested the levels of these candidate biomarkers in a selected cohort of SSc patients with short disease duration.
Objectives To determine whether plasma levels of selected candidate biomarkers of SSc disease activity are elevated in early SSc patients compared to healthy controls
Methods The biobank of the department of Rheumatology contains over 200 plasma samples of SSc patients. Twenty patients, with a disease duration of <3 years since first non-Raynaud symptom, were selected. Forty healthy, age and sex matched controls were collected via Sanquin bloodbank. Plasma biomarker levels were determined using Luminex kits, all measurements were performed in duplo. Medians of biomarker plasma levels were compared by using Mann-Whitney U tests.
Results Ratio of women to men was 13:7, mean ± SD age 49±12 years. Five patients were classified as the diffuse cutaneous (dc) SSc, 15 patients were classified as the limited cutaneous (lc) SSc. Median disease duration, from occurrence of the first non-Raynaud symptom was 13 (range 7 – 28) months. Skin involvement was variable (range 0-39), but most patients had stable modified Rodnan skin scores. Six patients showed signs of lung involvement, 1 of cardiac involvement. None of the patients had developed either pulmonary hypertension or scleroderma renal crisis.
As shown in table 1, plasma levels of selected candidate biomarkers of disease activity are compared between 20 SSc patients and 40 healthy controls. Levels of ET-1, IL-6, VEGF, ICAM-1 and VCAM-1 do not differ significantly in early lcSSc and dcSSc patients compared to healthy controls, although values tend to be higher. In addition, plasma levels in patients with interstitial lung disease (n=6) and cardiac involvement (n=1) were not significantly different from other SSc patients and healthy controls.
Conclusions In this cross-sectional study we found that the plasma levels of the selected candidate biomarkers of disease activity were not significantly higher in early lcSSc or dcSSc compared to healthy controls, though numerically levels tended to be higher.
A larger and preferably longitudinal study might be beneficial to find if the levels of these candidate biomarkers are increased in a subset of patients, in relation to prognosis, or if they increase with disease duration. Also, research should be expanded to identify other disease activity biomarkers.
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Disclosure of Interest None declared