Background Systemic sclerosis (SSc) is an autoimmune disease, characterized by widespread small vessel vasculopathy, immune dysregulation with production of autoantibodies, and progressive fibrosis. SSc may be associated with sicca syndrome. Changes in levels of proangiogenic and proinflammatory cytokines had already been determined largely in serum, however, the local inflammatory and cytokine milieu in the tear of SSc patients has not yet been evaluated.
Objectives We wished to determine VEGF and other cytokine and chemokine levels in tear samples of SSc patients.
Methods First, forty-three patients (40 female and 3 men, mean (SD) age 61 (48–74) years) with SSc and 27 healthy controls were enrolled in the VEGF study. Basal tear sample collection and tear velocity investigations were carried out followed by an ophthalmological examination. Total protein concentrations and VEGF levels were determined in tear samples. In the multiple cytokine study, unstimulated tear samples were collected from nine patients with SSc and 12 age- and gender-matched healthy controls. The relative levels of 102 different cytokines were determined by a cytokine array, and then absolute levels of four key cytokines were determined by a magnetic bead assay.
Results In the first study, the mean collected tear fluid volume developed 10.4 L (1.6–31.2) in patients and 15.63 L (3.68–34.5) in control subjects. The mean total protein level was 6.9 g/L (1.8–12.3) and 4.1 g/L (0.1–14.1) in tear samples of SSc patients and controls, respectively. In patients with SSc, the mean VEGF tear concentration was 4.9 pg/L (3.5–8.1) compared to 6.15 pg/L (3.84–12.3) in healthy samples. Multicytokine-array studies revealed shifted cytokine profile characterized by predominance of proinflammatory mediators in the tear samples of SSc patients. Out of the 102 analyzed proteins, nine were significantly increased in tears of patients with SSc. Based on the multiplex bead results, CRP, interferon-inducible protein 10 (IP-10) and monocyte chemoattractant protein-1 (mcp-1) levels were significantly higher in tears of patients with SSc compared to controls.
Conclusions Impaired angiogenesis has been found by other investigators in SSc. This is reflected by lower VEGF levels in the tear samples of SSc patients compared to controls. The multi-cytokine array study revealed increased production of CRP and two important pro-inflammatory chemokines in the tear of SSc patients. Our current data depict a group of inflammatory mediators, which may play a significant role in ocular pathology of SSc.
Disclosure of Interest None declared