Innate immune processes in lupus erythematosus

The innate immune system is involved in the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE) or dermatomyositis. The important role of complement factors of the classical pathway and of Toll like receptors (TLRs) is well established, based on genetic and clinical evidence. Immune complexes activate tumor necrosis factor (THE) in myeloid cells and interferon-alpha (IFN alpha) in plasmacytoid dendritic cells. The latter initiates a positive feedback loop that drives autoimmunity. More recently, mutations in genes encoding intracellular enzymes involved in RNA and DNA handling, which likewise lead to increased IFNa, have been found to cause familial chilblain lupus and to be associated with SLE. Within the immunological disease continuum, these disorders can be placed between autoinflammation and autoimmunity, and we would propose the term autoadjuvant for this group, since the activation of the innate immune system in these diseases appears to lower the threshold for (auto)immune reactions. (C) 2012 Elsevier Inc. All rights reserved.