Article
Sphingolipids and the IL-33/ST2 axis: Is there a link between these signaling pathways in the pathophysiology of systemic sclerosis?
Search Medline for
Authors
Published: | September 1, 2015 |
---|
Outline
Text
Background: Systemic sclerosis (SSc) is a clinically heterogeneous disease with an unclear etiology. It is mainly characterized by impaired angiogenesis and multi-organ fibrosis. The pathophysiology of SSc is not fully understood. First evidence indicates an involvement of both the IL-33/ST2 axis and of Sphingosine-1-phosphate (S1P) in the pathophysiological development of SSc. In this cooperative international clinical study we evaluted the hypothesis that components of the IL-33/ST2 or sphingolipid axis are involved in the pathophysiology or clinical course of SSc and how they relate to other recently derived biomarkers.
Results: In a cohort of German and Swedish SSc patients (87 serum and 175 plasma samples of SSc patients) we could confirm that S1P is elevated in lcSSc patients compared to control group (Tokumura et al., 2009) (lcSSc patients n = 175, control n = 112, p ≤ 0.001). S1P correlated with COMP serum levels (cartilage oligomeric matrix protein) (rs = 0.526, p ≤ 0.001, n = 95), a currently postulated marker for skin fibrosis, and with disease duration (rs = - 0.572, p ≤ 0.001, n = 95). More interestingly, S1P correlated inversely with the soluble IL-33 receptor sST2 (rs = 0.332, p ≤ 0.001, n = 95). We could demonstrate that serum sST2 was significantly and specifically raised in lcSSc patients with disease duration longer than 9 years compared lcSSc patients with shorter disease duration or dcSSc patients (lcSSc patients disease duration 1 - 3 years, n = 15, lcSSc patients disease duration ≥ 9 years, n = 29, p ≤ 0.01; dcSSc patients, n = 20 compared to lcSSc patients disease duration ≥ 9 years, p ≤ 0.01). Soluble ST2 correlated negatively with disease duration (rs = - 0.330, p ≤ 0.01, n = 97) in lcSSc and with nail fold capillaroscopy pattern (Cutolo et al., 2000) (early, n = 18 vs. late, n = 24, p ≤ 0.001).
Conclusion: These results support our assumption of a connection between S1P and sST2 in pathophysiology of SSc. Thus, sST2 and S1P are promising targets for further investigations with respect to unresolved questions of the SSc pathophysiology.