Abstract
The term spondyloarthritis (SpA) is used to describe a group of inflammatory autoimmune diseases, including ankylosing spondylitis and psoriatic arthritis, with common genetic risk factors and clinical features. SpA is clinically distinct from rheumatoid arthritis and typically affects the spine, sacroiliac joints, entheses, and, less commonly, peripheral joints. Although the pathogenesis of SpA is not fully understood, recent findings have identified the interleukin (IL)-17 pathway as a key mediator of disease pathogenesis. Clinical evidence for the efficacy of IL-17A inhibition by biologic agents was initially shown in patients with chronic plaque psoriasis, another autoimmune disease mediated by the IL-17 pathway. Subsequently, similar positive efficacy for inhibition of IL-17A was seen in patients with ankylosing spondylitis and psoriatic arthritis. Inhibition of IL-17A may also improve cardiovascular and metabolic comorbidities often found in patients with SpA because studies have linked these disorders to the IL-17 pathway. In this review, we will examine key preclinical studies that demonstrated the mechanistic role of IL-17A in the development SpA and discuss how these observations were translated into clinical practice.
Highlights
Spondyloarthritis (SpA) is a term used to describe a group of inflammatory autoimmune diseases that share common genetic risk factors and clinical features, including ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, undifferentiated SpA, and enteropathic arthritis [1,2,3,4,5,6]
This article provides a review of the pathogenesis of SpA and the mechanistic rationales for targeting the IL17A pathway based on its role in inflammation, cartilage damage, and bone changes
A study from our group that highlights the role of IL17A signaling in inflammatory arthritis showed that elevated levels of IL-17A and IL-17RA are present in synovial tissue samples from patients with PsA and, when cultures of these tissue samples were treated with an anti-IL-17RA antibody, IL-17A-induced expression of IL-8, IL-6, and matrix metalloproteinase (MMP)3 was decreased [33]
Summary
Spondyloarthritis (SpA) is a term used to describe a group of inflammatory autoimmune diseases that share common genetic risk factors and clinical features, including ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, undifferentiated SpA, and enteropathic arthritis [1,2,3,4,5,6]. Hallmark features of SpA include enthesitis, focal inflammation, new bone formation and cartilage ossification that may lead to ankyloses [2, 4, 7,8,9]. Cytokines produced by Thelper (Th) cells have been shown to contribute to pathogenic features of SpA, including joint erosion and inflammation, new bone formation, epidermal thickening, development of psoriatic skin lesions, pannus formation in joint capsules, synovial inflammation, and angiogenesis [7,8,9,10,11,12]. This article provides a review of the pathogenesis of SpA and the mechanistic rationales for targeting the IL17A pathway based on its role in inflammation, cartilage damage, and bone changes
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