Advances in understanding the pathophysiology of spondyloarthritis

Abstract

Progressive understanding of the underlying pathophysiology of axial spondyloarthritis has successfully translated into innovative therapeutic strategies and successful management of patients in the clinic. This review summarizes the key roles of pro-inflammatory cytokines tumor necrosis factor and interleukin-17 in the onset and progression of disease and how these cytokines are instrumental in shaping the concept that enthesitis is a key feature of axial spondyloarthritis. Advances in immunological technologies have lead to the important insight that different cell populations, part of both the innate and adaptive immune system, play a key role in axial spondyloarthritis. Besides inflammation, structural damage to the axial skeleton, in particular progressive ankylosis of the sacroiliac joints and the spine, is key to the outcome of patients. Novel data integrate the role of pro-inflammatory cytokines and enthesitis in this context.

Implication of IL-17 in Bone Loss and Structural Damage in Inflammatory Rheumatic Diseases

“…Therefore, the effect of the IL-17A blocking agent on the bone would be more relevant to study in patients with postmenopausal osteoporosis or in a subgroup of patients with significant bone loss. Second, new advances in the understanding of bone remodeling in spondyloarthropathies has shown that other factors other than inflammation (mechanical stress, microbiota) can play a major role in the development of the bone loss phenotype observed in patients [63]. Finally, translating data from mice to human is always challenging.…”

ATF6 aggravates angiogenesis-osteogenesis coupling during ankylosing spondylitis by mediating FGF2 expression in chondrocytes

“…The structural destruction and replacement of cartilage by granulation tissue is an important pathological change observed in AS patients. 11 Actually, an abnormal cartilage structure might be a common change before osteophyte formation. In 2009, Benjamin et al 34 applied IHC assay to spine osteophytes from the elderly and found a mixture of bone, cartilage, blood vessels and other tissues.…”

“…14,15 Taken together, these results suggest that blood vessel invasion is closed related to cartilage destruction and calcification. 11 However, the mechanism of blood vessel invasion remains unknown. As we showed above, Currently, whether ERS plays a role in AS development remains controversial.…”

“…Cartilage degradation and replacement by granulation tissue containing vessels is considered an important pathological change before joint ankylosis during AS. 1,11 The normal cartilage of an adult is avascular due to the presence of many factors that inhibit angiogenesis, including antiangiogenic protease inhibitors and chondromodulin-I (ChM-I), in the extracellular matrix. 12 However, previous studies showed that the amount of collagen was lower in the articular cartilage of AS patients than in non-AS individuals, indicating that the barrier function of cartilage to vessels might be altered in AS patients.…”

<p>Therapeutic Potential of Ixekizumab in the Treatment of Ankylosing Spondylitis: A Review on the Emerging Clinical Data</p>

“…[6][7][8] Over the last 20 years, the greatly improved knowledges of underlying pathogenic mechanisms of AS, including the role of tumor necrosis factor (TNF), the interleukin 23/Th17 axis, and interleukin-17 , constituted the rationale to develop biologics selectively inhibiting these pathways. 9 For more than 10 years, anti-TNF biologics were successfully employed to treat AS, with marked improvement of signs and symptoms in around 60% of the patients. 10 Moreover, these biologics were demonstrated to inhibit the radiographic progression of AS when employed in early phase of the disease.…”