Activation of the complement system in systemic sclerosis. Relationship to clinical severity

Abstract

Using newly developed techniques, we investigated the complement pathways and the extent of their activation in patients with systemic sclerosis (SSc) of both the diffuse cutaneous and limited cutaneous types. Plasma levels of the fragments C3d, C4d, and Ba were measured in patients with SSc and in matched control subjects. All fragments and ratios were higher in SSc patients than in controls (P < 0.05), demonstrating that complement activation occurs in SSc. Levels of C3d, C3d:C3, Ba, and Ba:factor B were higher in patients with diffuse cutaneous SSc than in those with limited SSc (P < 0.01). All fragments and ratios were higher in diffuse cutaneous SSc patients than in controls (P < 0.01). C3d, C3d:C3, C4d, and C4d:C4 levels were also higher in patients with limited cutaneous SSc than in controls (P < 0.05). These results show that complement activation occurs in SSc patients and that it reflects clinical severity. Complement activation may therefore

Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine, detected predominantly in systemic sclerosis sera, enhances proliferation of vascular endothelial cells

“…Increased serum concentrations of C1q, C2, C5, C6, C7, C9, and factor B and a decreased concentration of C4 have been observed in patients with SSc (25). Increased concentrations of C3d and C4d and increased ratios of C3d:C3 and C4d:C4 were reported to have a positive relationship with the severity of SSc (26). Another study also showed that an increased C3d level and markedly decreased complement level were dependent on prevention of immune precipitation in patients with SSc (27).…”

Renal biopsy findings predicting outcome in scleroderma renal crisis

“…Complement activation comparing systemic sclerosis patients with controls has been reported [27,28]. We assessed endothelial C4d deposition, an early classic complement pathway marker, using a polyclonal antibody immunostain.…”

The complement system in systemic autoimmune disease

“…C3d, C3d/C3, C4d, and C4d/C4 levels were also higher in patients with limited cutaneous SSc than in normal controls. These data suggest that complement activation occurs in SSc patients and reflects clinical severity [93]. Complement activation via the classical pathway may therefore have a pathogenetic role in SSc, and its measurement may prove useful in monitoring the disease [93], although these data should be confirmed in large, prospective studies.…”