Potential role of the lectin pathway of complement in the pathogenesis and disease manifestations of systemic sclerosis: A case-control and cohort study

Abstract

Introduction: Repetitive episodes of ischemia and reperfusion (I/R) are a cardinal feature of the pathogenesis of systemic sclerosis (SSc), which precedes tissue fibrosis. The complement system is a key mediator of tissue damage after I/R, primarily by activation of the lectin pathway. This study investigated whether serum levels and polymorphisms of mannose-binding lectin (MBL) and ficolin-2 (FCN2), two pattern recognition receptors of the lectin pathway, are associated with the predisposition to and clinical features of SSc. Methods: A case-control study was undertaken involving 90 patients with SSc from a single SSc outpatient clinic and 90 age- and sex-matched blood donors. MBL and FCN2 levels and polymorphisms were measured in both groups, and in cases correlated with clinical data. Results: MBL levels and genotypes were equally distributed in cases and controls while there were some significant differences in FCN2 polymorphisms. Median MBL levels were higher in SSc cases with diffuse disease compared with controls (2.6 versus 1.0μg/ml, P <0.001). Conclusions: Overall, predisposition to SSc was not influenced by the lectin pathway of complement in our matched case-control study. However, our preliminary data suggest that MBL, and to a lesser extent FCN2, may modulate disease manifestations of SSc, particularly in diffuse cutaneous disease.