Does the microbiome play a causal role in spondyloarthritis?

Rosenbaum, James T.; Lin, Phoebe; Asquith, Mark; Costello, Mary Ellen; Kenna, Tony J.; Brown, Matthew A.

doi:10.1007/s10067-014-2664-5

Cited by 28 publications

(10 citation statements)

References 42 publications

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“…It has been sug gested that the underlying immunogenetic profile of AS, including the association with HLA-B*27, might cause AS by interacting with the gut microbiome directly. 56,[59][60][61] The presence or absence of microbes has profound effects on disease development in the HLA-B*27transgenic rat model of spondyloarthritis, as disease fails to develop if HLA-B*27transgenic rats are bred in a germfree environment. 62 Similarly, in the SKG mouse model of spondyloarthritis, germfree conditions dampen disease considerably and reduce ileal IL23 expression.…”

Section: Progress In Non-mhc Geneticsmentioning

confidence: 99%

Genetics of ankylosing spondylitis—insights into pathogenesis

2015

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Ankylosing spondylitis (AS), an immune-mediated arthritis, is the prototypic member of a group of conditions known as spondyloarthropathies that also includes reactive arthritis, psoriatic arthritis and enteropathic arthritis. Patients with these conditions share a clinical predisposition for spinal and pelvic joint dysfunction, as well as genetic associations, notably with HLA-B(*)27. Spondyloarthropathies are characterized by histopathological inflammation in entheses (regions of high mechanical stress where tendons and ligaments insert into bone) and in the subchondral bone marrow, and by abnormal osteoproliferation at involved sites. The association of AS with HLA-B(*)27, first described >40 years ago, led to hope that the cause of the disease would be rapidly established. However, even though many theories have been advanced to explain how HLA-B(*)27 is involved in AS, no consensus about the answers to this question has been reached, and no successful treatments have yet been developed that target HLA-B27 or its functional pathways. Over the past decade, rapid progress has been made in discovering further genetic associations with AS that have shed new light on the aetiopathogenesis of the disease. Some of these discoveries have driven translational ideas, such as the repurposing of therapeutics targeting the cytokines IL-12 and IL-23 and other factors downstream of this pathway. AS provides an excellent example of how hypothesis-free research can lead to major advances in understanding pathogenesis and to the development of innovative therapeutic strategies.

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Section: Progress In Non-mhc Geneticsmentioning

confidence: 99%

Genetics of ankylosing spondylitis—insights into pathogenesis

2015

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“…Some hypothesize that HLA-B27 leads to mucosal immunodeficiency secondary to effects on intestinal permeability or alterations in the gut microbiome such as a loss of protective bacterial species (16). Using stool and blood samples Stoll et al demonstrated that in comparison to controls, ERA patients had decreased levels of F. prausnitzii (17).…”

Section: Genetics and Pathogenesismentioning

confidence: 99%

Juvenile spondyloarthritis

Gmuca

Weiss

2015

Current Opinion in Rheumatology

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Purpose of review To provide a comprehensive update of the pathogenesis, diagnostic imaging, treatments, and disease activity measurements of juvenile spondyloarthritis (JSpA). Recent findings Genetic and microbiome studies have provided new information regarding possible pathogenesis of JSpA. Recent work suggests that children with JSpA have decreased thresholds for pain in comparison to healthy children. Additionally, pain on physical examination and abnormalities on ultrasound of the entheses are not well correlated. Treatment guidelines for juvenile arthritis, including JSpA, were published by the American College of Rheumatology and are based on active joint count and presence of sacroiliitis. Recent studies have established the efficacy of tumor necrosis factor inhibitors in the symptomatic treatment of axial disease, though their efficacy for halting progression of structural damage is less clear. Newly developed disease activity measures for JSpA include the Juvenile Arthritis Disease Activity Score and the JSpA Disease Activity index. In comparison to other categories of juvenile arthritis, children with JSpA are less likely to attain and sustain inactive disease. Summary Further microbiome and genetic research may help elucidate JSpA pathogenesis. More randomized therapeutic trials are needed and the advent of new composite disease activity measurement tools will hopefully allow for the design of these greatly needed trials.

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“…The development of state-of-the-art 16S rRNA high-throughput sequencing technology for microbial profiling has opened the door for the characterization of the phylogenetic distribution of taxa in the gut bacterial communities in an individual. With this culture-independent approach, an increasing number of reports have documented decreases in gut microbiome diversity and other forms of dysbiosis in inflammatory and autoimmune diseases that include RA 9,10,11 , psoriatic arthritis 12 , AS 13 , and inflammatory bowel disease (IBD) 14 .…”

Section: Is Gut Microbial Lps a Potential Trigger Of Juvenile Idiopatmentioning

confidence: 99%