Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 44, Issue 6, Pages 1593-1599Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201444486
Keywords
Animal models; Autoimmunity; Rheumatology
Categories
Funding
- KA Wallenberg foundation
- Swedish Research Council
- Swedish Strategic Foundation (SSF)
- European Union [IMI-115142]
- German Federal Ministry of Education and Research ArthroMark [01 EC 1009C]
- Federal State of Hesse
- German Research Foundation (DFG) [BU 584/4-1]
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Extensive genome-wide association studies have recently shed some light on the causes of chronic autoimmune diseases and have confirmed a central role of the adaptive immune system. Moreover, better diagnostics using disease-associated autoantibodies have been developed, and treatment has improved through the development of biologicals with precise molecular targets. Here, we use rheumatoid arthritis (RA) as a prototype for chronic autoimmune disease to propose that the pathogenesis of autoimmune diseases could be divided into three discrete stages. First, yet unknown environmental challenges seem to activate innate immunity thereby providing an adjuvant signal for the induction of adaptive immune responses that lead to the production of autoantibodies and determine the subsequent disease development. Second, a joint-specific inflammatory reaction occurs. This inflammatory reaction might be clinically diagnosed as the earliest signs of the disease. Third, inflammation is converted to a chronic process leading to tissue destruction and remodeling. In this review, we discuss the stages involved in RA pathogenesis and the experimental approaches, mainly involving animal models that can be used to investigate each disease stage. Although we focus on RA, it is possible that a similar stepwise development of disease also occurs in other chronic autoimmune settings such as multiple sclerosis (MS), type 1 diabetes, and systemic lupus erythematosus.
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