Ankylosing spondylitis (AS) is a common immune-mediated inflammatory arthritis with a strong genetic predisposition. We review recent data from genetic and animal studies highlighting the importance of Type 17 immune responses. Furthermore, the efficacy (or lack thereof) of different anti-cytokine monoclonal antibodies has highlighted the diversity of Type 17 immune cells and cytokines critical to AS and related spondyloarthritis pathogenesis. Recent studies have strongly implicated the gut microbiome in AS. Finally, we propose that the local metabolic environment of the joint may have a key role in driving AS, and present a novel model of AS pathogenesis.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/imm.13242

New developments in our understanding of ankylosing spondylitis pathogenesis.

Ankylosing spondylitis (AS) is a type of axial inflammation. Over time, some patients develop spinal ankylosis and permanent disability; however, current treatment strategies cannot arrest syndesmophyte formation completely. Here, we used mesenchymal stem cells (MSCs) from AS patients (AS MSCs) within the enthesis involved in spinal ankylosis to delineate that the HLA-B27-mediated spliced X-box-binding protein 1 (sXBP1)/retinoic acid receptor-β (RARB)/tissue-nonspecific alkaline phosphatase (TNAP) axis accelerated the mineralization of AS MSCs, which was independent of Runt-related transcription factor 2 (Runx2). An animal model mimicking AS pathological bony appositions was established by implantation of AS MSCs into the lumbar spine of NOD-SCID mice. We found that TNAP inhibitors, including levamisole and pamidronate, inhibited AS MSC mineralization in vitro and blocked bony appositions in vivo. Furthermore, we demonstrated that the serum bone-specific TNAP (BAP) level was a potential prognostic biomarker to predict AS patients with a high risk for radiographic progression. Our study highlights the importance of the HLA-B27-mediated activation of the sXBP1/RARB/TNAP axis in AS syndesmophyte pathogenesis and provides a new strategy for the diagnosis and prevention of radiographic progression of AS.

/pdf/hla-b27-mediated-activation-of-tnap-phosphatase-promotes-38qheid2e1.pdf

HLA-B27–mediated activation of TNAP phosphatase promotes pathogenic syndesmophyte formation in ankylosing spondylitis

Radiographic axial spondyloarthritis (also known as ankylosing spondylitis [AS]) is a chronic immune-mediated arthritis characterized by inflammation of the axial skeleton, peripheral joints, and entheses. It is estimated that 1 in every 200 people are affected by AS, making it an important healthcare and socioeconomic issue. In this review, we aim to explore the current understanding of AS risk factors and provide a comprehensive update. Multiple search strings were used to identify articles of interest published in PubMed between January 1, 2013, and February 1, 2021. On the basis of the literature review and analysis, we present up-to-date information on the risk factors of developing AS and our viewpoints on disease onset and progression. Multiple genetic and nongenetic risk factors have been suggested in the onset of AS. HLA-B27 is known to have a strong association with the disease, but other genes have been implicated in disease development. Aside from genetics, other factors are thought to be involved; up to 70% of patients with AS have subclinical intestinal inflammation, suggesting that the origin of the disease may be in the gut. The exact mechanism by which AS onset begins is most likely complex and multifactorial. Key Points • It remains unclear how interactions between genes, microbes, mechanical stress, gender, and other environmental and lifestyle factors predispose patients to the development of ankylosing spondylitis (AS). • The exact mechanisms of AS are complex and multifactorial which will require much future research • Recognizing the risk factors, as well as understanding gene-environment interactions, may offer valuable insights into the etiology of AS and have important implications for diagnosis and treatment strategies.

Ankylosing spondylitis risk factors: a systematic literature review.

Immunological and oxidative stress biomarkers in Ankylosing Spondylitis patients with or without metabolic syndrome.

Tripteryguim wilfordii Hook (TWH) has significant anti-inflammatory and immunosuppressive properties and is widely used for treating autoimmune and inflammatory diseases. However, the multi-target ...

Multi-target mechanism of Tripteryguim wilfordii Hook for treatment of ankylosing spondylitis based on network pharmacology and molecular docking

AS is a common rheumatic condition characterized by inflammation and new bone formation. The pathogenesis of AS is likely multifactorial and has not been fully elucidated to date. A major genetic role has been demonstrated. The strongest genetic association is with HLA B27. Numerous other associated genetic polymorphisms have been identified, including those affecting the type 17 immune pathway, although the precise link between genetics and pathogenesis remains unexplained. Several immunological alterations, together with recent therapeutic advances, support a central role for IL-23- and IL-17-producing immune cells in disease pathogenesis. Recently, perturbations of gut microbiota of AS patients have further catalysed research and offer potential for future therapeutic intervention. In this review we outline the genetic basis of AS and describe the current hypotheses for disease pathogenesis. We synthesize recent experimental research data and clinical studies to support a central role for the type 17/23 immune axis in AS.

/pdf/progress-in-our-understanding-of-the-pathogenesis-of-47akm0q9q6.pdf

M Hussein Al Mossawi

Papers

Progress in our understanding of the pathogenesis of ankylosing spondylitis.