Frédéric Coutant1,2, Pierre Miossec1,3. 1. Immunogenomics and Inflammation Research Unit EA4130, University of Lyon, Edouard Herriot Hospital, Lyon. 2. Immunology Department, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite. 3. Department of Immunology and Rheumatology, Edouard Herriot Hospital, Lyon, France.
Abstract
PURPOSE OF REVIEW: To provide an overview of recently published work covering key mechanisms involved in the pathogenesis of rheumatoid arthritis (RA), with focus on the early and late stages. RECENT FINDINGS: Present understanding of RA pathogenesis has been mainly focused on the inflammatory process at the established phase of the disease, but recent work has shed light on important molecular and cellular mechanisms involved both at the early and late/refractory stages. In early RA, the involvement of anticitrullinated protein antibodies in RA induction has been identified with a critical role of the IL-23/Th17 axis in the control of their pathogenicity. At the late stage, RA may be viewed as a cell-autonomous genetic and epigenetic disease, characterized by altered cell death pathways in synoviocytes after long-term exposure to inflammation. An improved knowledge of these cell-intrinsic altered pathways is the basis for the targeting of pathogenic synoviocytes, as a new therapeutic alternative against resistance to current treatment targeting the immune system. SUMMARY: We summarize these pathological pathways, and their understanding will facilitate the design of new diagnostic tools and therapeutic strategies combining the targeting of pathogenic synoviocytes with current immune-targeted therapies.
PURPOSE OF REVIEW: To provide an overview of recently published work covering key mechanisms involved in the pathogenesis of rheumatoid arthritis (RA), with focus on the early and late stages. RECENT FINDINGS: Present understanding of RA pathogenesis has been mainly focused on the inflammatory process at the established phase of the disease, but recent work has shed light on important molecular and cellular mechanisms involved both at the early and late/refractory stages. In early RA, the involvement of anticitrullinated protein antibodies in RA induction has been identified with a critical role of the IL-23/Th17 axis in the control of their pathogenicity. At the late stage, RA may be viewed as a cell-autonomous genetic and epigenetic disease, characterized by altered cell death pathways in synoviocytes after long-term exposure to inflammation. An improved knowledge of these cell-intrinsic altered pathways is the basis for the targeting of pathogenic synoviocytes, as a new therapeutic alternative against resistance to current treatment targeting the immune system. SUMMARY: We summarize these pathological pathways, and their understanding will facilitate the design of new diagnostic tools and therapeutic strategies combining the targeting of pathogenic synoviocytes with current immune-targeted therapies.