IMMUNOPATHOGENESIS AND THERAPY OF SYSTEMIC LUPUS-ERYTHEMATOSUS

The aetiopathogenesis of systemic lupus erythematosus (SLE) is thought to comprise the combined action of hormonal influences and other fact ors, partly of exogenous and partly of endogenous nature, which leads to the production of autoantibodies and/or lymphoid cells, resulting i n inflammatory processes, The fundamental characteristic is the occurr ence in blood of autoantibodies against intranuclear cell components, usually designated as antinuclear antibodies, In addition, autoantibod ies against cytoplasmically located antigens occur, Antibodies to DNA are the most prominent examples of autoantibodies, the most typical of which in SLE are antibodies to double-stranded DNA. Antibodies direct ed against different components of ribonucleoprotein particles include the anti-Sm, anti-SS-A (Ro) and anti-SS-B (La) antibodies. Antihiston e antibodies directed against DNA-binding proteins, in particular agai nst various histones, occur frequently in patients with drug-induced l upus, Antiphospholipid antibodies, notably lupus anticoagulant and ant icardiolipin antibodies, are strongly associated with the antiphosphol ipid syndrome, but these antibodies can also occur in patients without features of lupus. This wide spectrum of autoantibodies implies a mar ked degree of chronic B lymphocyte activity. The question is whether t hese findings point to an intrinsic B cell aberration, There is also c onsiderable evidence for a role of T cells in the pathogenesis of SLE, In addition, unbalanced cytokine production seems to occur, The disea se also has genetic and gender aspects, and its activity may be modula ted by sex hormones. Unfortunately, as the aetiology of SLE is still o bscure and the pathogenetic mechanisms leading to organ disease not we ll understood, therapy is still limited to the use of agents with rath er nonspecific anti-inflammatory properties, such as antimalarials, co rticosteroids. cytotoxic drugs and apheresis. Most of these therapeuti c modalities may not only benefit but also cause serious adverse effec ts. The eventual aim is to design immune intervention strategies, such as specific blocking peptides, by which harmful immune reactions will be eliminated leaving host defence immune reactivity intact. However, the most logical approach for immune intervention in the treatment of SLE has still to be defined.