Editorial [Hot topic: Drug Targeting of Autoimmunity (Guest Editor: Manfred Kunz)]

Chronic inflammatory and autoimmune diseases are a major cause of morbidity and mortality in the industrialized world, affecting 3 to 8 % of the population. The wide spectrum of these diseases includes rheumatoid arthritis, systemic lupus erythematosus, psoriasis, multiple sclerosis, type-1 diabetes, Crohn's disease, and systemic sclerosis. Besides apparent clinical differences, there are also many clinical and pathogenic overlaps supported by the fact that they co-occur in a significant number of patients. For example, co-occurrence of type-1 diabetes, autoimmune thyroiditis, rheumatoid arthritis, coeliac disease and multiple sclerosis has been described. Furthermore, there is compelling evidence for a central role of so-called Th17 T cells in the immunopathogenesis of these diseases. Th17 cells have been recently identified as effector CD4+ Th cells, defined by their production of IL-17A and IL-17F, two inflammatory cytokines which are normally not produced by Th1 or Th2 cells. After IL-23 stimulation, this new type of T cells produces a range of further inflammatory mediators such TNF-α, IL-6, IL-21, IL-22 and CCL20. Recent genetic studies have shown that many of the mentioned diseases have a strong genetic background with some overlapping genetic patterns. Systematic genome-wide association studies have been performed to test common genetic variants (e.g., single nucleotide polymorphisms) for association to disease risk of the mentioned diseases. Independent risk alleles were identified at the IFN regulatory factor 5 (IRF5) locus for systemic lupus erythematosus and at the IL23R locus for Crohn's disease. Single nucleotide polymorphisms in the STAT4 (signal transducer and activator of transcription 4) gene were described to be associated with rheumatoid arthritis and systemic lupus. Treatment of autoimmune diseases has long been based on non-specific anti-inflammatory drugs. This has changed dramatically in recent years with the development of neutralizing antibodies and soluble receptor molecules targeting inflammatory cytokines or immune cell receptors, and the use of tolerizing autoantigens, all of which specifically downmodulate immune responses. Historically, a major breakthrough was the observation that the expression of major pro-inflammatory cytokines IL- 1, IL-6, IL-8, and GM-CSF, produced by synoviocytes from RA patients, could be blocked by addition of a TNF-neutralizing antibody. This observation laid the foundation for the development of TNF-neutralizing biological agents, which were applied soon thereafter in humans for variety of chronic inflammatory and autoimmune diseases. In this issue of the journal, we will give an overview of current treatment of autoimmune diseases such as psoriasis, bullous autoimmune diseases, Crohn's disease, lupus erythematosus and autoimmune vasculitides, with a special emphasis on biologics. This includes recent progresses in treatment of bullous autoimmune diseases using immune absorption combined with biological agents. Moreover, we present the current status of experimental mouse models of autoimmunity with a focus on mouse genetics. Finally, we will describe the potential of current metabolomics technologies for disease and treatment monitoring. Taken together, treatment modalities of chronic inflammatory and autoimmune diseases have dramatically improved in recent years, but there is still a plethora of new targets for further innovative treatment approaches.