Complement mediated vascular endothelial injury in rheumatoid nodules: A histopathological and immunohistochemical study

Objective. To evaluate morphologically and immunohistochemically the role of IgM rheumatoid factor (RF) immune complexes and complement activation in rheumatoid nodule vascular injury, a typical extraarticular manifestation of rheumatoid arthritis. Methods. Histological features such as cellular infiltration, endothelial alteration, fibrinoid degeneration, and basement membrane alterations were observed in the small vessels in rheumatoid nodules. An immunohistochemical study was also carried out. Results. Distinct colocalization of IgM RF and terminal complement complexes (TCC: C5b-9) was observed on the luminal surface in some of the damaged endothelial cells. Immune-electron microscopy revealed endothelial vesiculation, typical of the in vitro protective mechanism against complement attack, with deposition of not only TCC but also IgM RE Most TCC positive endothelial cells simultaneously expressed the major complement regulatory factor, CD59. Conclusion. These data suggest that, in rheumatoid nodules, vascular injury mediated by complement activation involves the assembly of IgM RF on the endothelial cell surface.