Arthritis & rheumatology (Hoboken, N.J.)
-
Arthritis Rheumatol · Mar 2021
ReviewNew Therapeutic Targets in Antineutrophil Cytoplasm Antibody-Associated Vasculitis.
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a rare systemic autoimmune disease that is characterized by necrotizing inflammation of predominantly the small blood vessels and the presence of circulating ANCAs directed against myeloperoxidase or proteinase 3. Current treatment strategies for severe disease, supported by the findings of several well-coordinated randomized controlled trials, aim to induce remission with high-dose glucocorticoids and either rituximab or cyclophosphamide, followed by relapse prevention with a period of sustained low-dose treatment. ⋯ Recent advances in our understanding of the pathogenesis of AAV have led to the identification of novel therapeutic targets that may address these problems, including strategies directed at the aberrant adaptive autoimmune response (B and T cell-directed treatments) and those targeting innate immune elements (complement, monocytes, and neutrophils). It is anticipated that these novel treatments, used alone or in combination, will lead to more effective and less toxic treatment regimens for patients with AAV.
-
Arthritis Rheumatol · Jan 2021
ReviewThe Longitudinal Immune Response to Coronavirus Disease 2019: Chasing the Cytokine Storm.
The clinical progression of the severe acute respiratory syndrome coronavirus 2 infection, coronavirus 2019 (COVID-19), to critical illness is associated with an exaggerated immune response, leading to magnified inflammation termed the "cytokine storm." This response is thought to contribute to the pathogenicity of severe COVID-19. There is an initial weak interferon response and macrophage activation that results in delayed neutrophil recruitment leading to impeded viral clearance. This causes prolonged immune stimulation and the release of proinflammatory cytokines. ⋯ The progression to severe disease is accompanied by endotheliopathy, immunothrombosis, and hypercoagulability. Thus, both parts of the immune system-innate and adaptive-play a significant role in the cytokine storm, multiorgan dysfunction, and coagulopathy. This review highlights the importance of understanding the immunologic mechanisms of COVID-19 as they inform the clinical presentation and advise potential therapeutic targets.