Background Systemic sclerosis (SSc) is a complex inflammatory autoimmune disease characterized by excessive fibrosis and vascular changes in the skin and in other visceral organs. Although the pathogenesis of SSc remains unclear, infiltration of monocytes/macrophages and T cells into the tissue plays a critical role in the organ involvement probably through the production of soluble mediators, including cytokines and chemokines.
Objectives The present study sought to determine wheter serum levels of 5 chemokines and 5 cytokines are elevated and wheter there is a different profile in SSc patients grouped according to SSc associated autoantibody subsets and the organ involvement.
Methods Serum levels of CXCL/IL8, CXCL9/Mig, CCL2/MCP1, CXCL10/IP-10, CCL5-RANTES, IL-1β, IL-6, IL-10, TNFα, IL-12 were measured by cytometric beads array kits using a FACScan flow cytometer (BD PharMingen) in 19 SSc patients and 14 healthy controls (aged 54±11,2, female 8, male 6). SSc patients were grouped according to the extent of cutaneous involvement, the pattern of organ involvement and the autoantibodies: diffuse cutaneous SSc (dcSSc, n=11, aged 51±8.6 years, female 9,male 2) with anti-topoisomerase antibodies (ATAs) and limited cutaneous SSc (lcSSc, n=8, aged 60±8.6 years, female 6, male 2) with anti-centromere antibodies (ACAs). Three lcSSc patients and 1 dcSSc patient had esophageal dysfunction; 2 lcSSc patients had a definite diagnosis of primary biliary cirrhosis (PBC). The dsSSC group consisted of 2 patients with arthritis; isolated interstitial pneumonia in a patient and associated with pulmonary hypertension and Sjögren’s Syndrome in 2 patients.
Results Serum levels of CXCL/IL-8, CCL5-RANTES, CXCL9/Mig were found to be higher in patients with SSc than in controls. Furthermore the levels of CXCL/IL-8 and of CXCL9/Mig increased significantly in dcSSc patients with isolated interstitial pneumonia or associated with pulmonary hypertension or Sjögren’s Syndrome. The elevation of CCL5-RANTES correlates with the esophageal involvement in patients with dc or lcSSC and correlates with liver damage. There were no significant differences in the levels of CCL2/MCP1, CXCL10/IP-10 compared to controls. However, serum levels of cytokines were undetectable in patients and in healthy controls by this method.
Conclusions Our data confirm that the elevation of serum levels of CXCL/IL-8, CCL5-RANTES, CXCL9/Mig correlate with visceral involvement in SSc patients. Moreover, this report suggests that CCL5-RANTES had been shown to be highly expressed in esophageal damage and in PBC. These findings highlight the complex immunopathogenesis of SSc and point the several targets that could be considered for monitoring disease progression and treatment of SSc.
Serum chemokines and cytokines levels as indicators of disease activity in patients with systemic sclerosis. Hasegawa M, et al. Clin Rheumat 2011;30(2):231-7.
Plasma cytokine profiles in Systemic Sclerosis: association with autoantibody subsets and clinical manifestations. Gourh P, et al. Arthritis Res Ther 2009;11(5):R147.
The pronounced Th17 profile in Systemic Sclerosis together with intracellular expression of TGFβ and IFNγ distinguishes SSc phenotypes. Radstake TR, et al. PLoS One 2009;17;4(6): 5903.
Disclosure of Interest None Declared