Pathogenetic insights from the treatment of rheumatoid arthritis

Rheumatoid arthritis is a chronic autoimmune disease that causes progressive articular damage, functional loss, and comorbidity. The development of effective biologics and small-molecule kinase inhibitors in the past two decades has substantially improved clinical outcomes. Just as understanding of pathogenesis has led in large part to the development of drugs, so have mode-of-action studies of these specific immune-targeted agents revealed which immune pathways drive articular inflammation and related comorbidities. Cytokine inhibitors have definitively proven a critical role for tumour necrosis factor α and interleukin 6 in disease pathogenesis and possibly also for granulocyte-macrophage colony-stimulating factor. More recently, clinical trials with Janus kinase (JAK) inhibitors have shown that cytokine receptors that signal through the JAK/STAT signalling pathway are important for disease, informing the pathogenetic function of additional cytokines (such as the interferons). Finally, successful use of costimulatory blockade and B-cell depletion in the clinic has revealed that the adaptive immune response and the downstream events initiated by these cells participate directly in synovial inflammation. Taken together, it becomes apparent that understanding the effects of specific immune interventions can elucidate definitive molecular or cellular nodes that are essential to maintain complex inflammatory networks that subserve diseases like rheumatoid arthritis

Kruskal's Tree Theorem for Acyclic Term Graphs

In this paper we study termination of term graph rewriting, where we restrict our attention to acyclic term graphs. Motivated by earlier work by Plump we aim at a definition of the notion of simplification order for acyclic term graphs. For this we adapt the homeomorphic embedding relation to term graphs. In contrast to earlier extensions, our notion is inspired by morphisms. Based on this, we establish a variant of Kruskal's Tree Theorem formulated for acyclic term graphs. In proof, we rely on the new notion of embedding and follow Nash-Williams' minimal bad sequence argument. Finally, we propose a variant of the lexicographic path order for acyclic term graphs.Comment: In Proceedings TERMGRAPH 2016, arXiv:1609.0301

Osteoimmunology in rheumatic diseases

This review summarizes the recent advances of osteoimmunology, a new research field that investigates the interaction of the immune system with the skeleton. Osteoimmunology has contributed significantly to the understanding of joint destruction in rheumatoid arthritis and other forms of arthropathies. In particular, the molecular regulation of osteoclast formation and its control by proinflammatory cytokines have helped investigators to understand the mechanisms of bone erosion in rheumatic diseases. Osteoimmunology has also allowed an improvement in our knowledge of the structure-sparing effects of antirheumatic drug therapy. Moreover, recent advances in the understanding of the molecular regulation of osteophyte formation are based on the characterization of the regulation of bone formation by inflammation. This review highlights the key insights into the regulation of bone destruction and formation in arthritis. Moreover, concepts of how bone influences the immune system are discussed