Detection of activated complement complex C5b-9 and complement receptor C5a in skin biopsies of patients with systemic sclerosis (scleroderma)

Objective. Upregulated matrix synthesis is a hallmark of systemic sclerosis (SSc), There are indications that growth factors such as platelet derived growth factor (PDGF) are involved in proliferative pathways in SSc lesions. As activated complement releases PDGF from endothelial cells, we searched for activated complement and the complement receptor for C5a (C5aR) in skin biopsies of patients with SSc. Methods. Snap frozen sections of 8 patients with early SSc and 5 patients w ith longterm SSc were examined. Using monoclonal antibodies against activat ed complement complex C5b-9 and the C5aR, skin biopsies derived from both c linically involved and non-involved skin were examined by APAAP immunohisto chemistry. Results. A pattern of activated complement C5b-9 and the C5aR could be dete cted in SSc microvasculature. Eleven of the 13 patients (7/8 patients with early SSc) showed positive staining for C5b-9. The C5aR was detected in 6 o f the 8 patients with early SSc. In 3 patients with longterm disease, C5aR expression could also be detected in non-involved skin. Conclusion. Activated complement and complement receptors could be detected in early and late stages of SSc skin lesions. The presence of complement r eceptors in non-involved skin may indicate preclinical activation of pathwa ys resulting in growth factor dependent matrix synthesis.