The aetiology of the primary
systemic vasculitides remains obscure. Recent years have seen significant advances in our understanding of
inflammation and in particular the role of and interaction between the vascular endothelium, mediators and immune effector cells. This has helped to further elucidate those specific processes relevant to
vasculitis which result in endothelial cell damage. In
Wegener's granulomatosis and microscopic polyarteritis the evidence favours an autoimmune inflammatory response characterised by specific mediators in which the endothelium is both target and active participant. Current treatment of these disorders with combinations of
corticosteroids and cytotoxics is highly effective in inducing remission. However, long-term use of this
therapy is potentially toxic and there remains also a significant risk of relapse. It is hoped that increased understanding of the pathogenesis of
systemic vasculitis will enable more specific, less toxic and more effective
therapies to be defined. Jayne et al. have suggested a beneficial effect of intravenous pooled normal human
immunoglobulin (
IVIG) in patients with
ANCA-positive
vasculitis. In vitro studies have shown that
IVIG contains antiidiotypic
antibodies to
ANCA and
AECA, capable of inhibiting the binding of these
autoantibodies to their
autoantigens. In vivo,
IVIG may also provide the immunoregulatory elements needed for the idiotype network and control of the autoimmune repertoire. Mathieson et al. successfully used
monoclonal antibodies to T cells (
Campath-H directed against CDw52) in a patient with
ANCA-negative dermal lymphocytic
vasculitis.
Monoclonal antibodies to CAMs have been used in human renal transplant rejection and reduced the
inflammation and
proteinuria in animal models of
anti-glomerular basement membrane disease. In
vasculitis, the
therapeutic use of specific anti-CAM
antibodies may result from further definition of the role of CAMs. Increased understanding of the pathogenesis of
systemic vasculitis is likely to provide the basis for the use of more specific
immunotherapies in the future.