Systemic Lupus Erythematosus — is a Viral Aetiology a Credible Hypothesis?

Abstract

Systemic lupus erythematosus (SLE) is still regarded as a paradigm for autoimmune diseases, an Everest which if conquered would allow the solution of other unsolved problems in autoimmunity. Thus, interest in this issue is not confined to physicians and medical scientists who deal directly with patients with this disorder. The seach for viral causes of SLE has continued despite many decades of largely fruitless endeavour. Indeed, interest in this possibility has been sustained mainly by the discovery of the many mechanisms in natural infections and model systems by which persistently infective viruses are able to evade elimination by host immune defences and to stimulate autoimmune phenomena or disease. 1,2 Of particular relevance to the immunopathogenesis of SLE are those viral infections which induce the characteristic spectrum of anti-nuclear and related autoantibodies and also lesions related to immune complex deposition and cytokine-induced inflammation resembling those characteristic of human SLE. For example, viral infections reveal cryptic auto-antigens to the immune system, thereby allowing tolerance to these antigens to be broken. 3 The inflammatory reaction accompanying many viral infections generates high local concentrations of pro-inflammatory cytokines with subsequent autoantibody production. 4,5 Such findings mirror the many situations in which transgenic manipulation of constitutive cytokine production is followed by autoimmune disorders. More simplistically, in clinical medicine parvovirus B19 infection is a telling example of a situation in which an ubiquitous agent induces acute clinical features and immunological abnormalities closely resembling SLE, often over a period of many months. 6