Intestinal and enthesis innate immunity in early axial spondyloarthropathy

Sharif, Κassem; Bridgewood, Charlie; Dubash, Sayam; McGonagle, Dennis

doi:10.1093/rheumatology/keaa408

Cited by 19 publications

(13 citation statements)

References 83 publications

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“…Indeed, a reevaluation of MRE in a cohort of children with IBD showed that, using the ASAS (Assessment of SpondyloArthritis international Society) criteria for signs of sacroiliitis, 15% of patients have mild sacroiliitis at MRE despite not complaining of any musculoskeletal symptoms [ 45 ]. The link between IBD and joint/bone inflammation might rely on the alteration of IL-23 and/or IL-17 axis, dysbiosis, and subclinical gut barrier dysfunction as well as genetic factors such as the HLA B27 positivity and NOD2 variants [ 46 , 47 ].…”

Section: Introductionmentioning

confidence: 99%

Chronic Nonbacterial Osteomyelitis and Inflammatory Bowel Disease: A Literature Review-Based Cohort

et al. 2023

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Background: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder that mainly involves children and adolescents. The association with other inflammatory disorders, such as inflammatory bowel disease (IBD), psoriasis, and arthritis, has been reported in the literature. In particular, the relationship between bone and intestinal inflammation is still poorly understood. For this purpose, our review aims to describe the cases reported in the literature concerning this association and to compare them with data from our single-center cohort of patients. Methods: We conducted a literature review of published cases of CNO associated with IBD. Eligible articles were identified through a Medline search in the PubMed database until December 2022. We retrospectively reviewed medical records of patients with CNO referred to G. Pini Hospital and compared them with the literature-review-based cohort. Results: Fifty-seven patients with a defined diagnosis of CNO and associated IBD were described in the literature (female 55%). The median age of onset of the disease (CNO or IBD) was 11 years. In 32/53 (60%), a diagnosis of Crohn’s disease (CD) was made, while 18 (34%) patients were classified as suffering from ulcerative colitis (UC) and 3 (6%) from undifferentiated IBD. The diagnosis of CNO preceded the diagnosis of IBD in 59% of cases; while in 24%, IBD anticipated CNO; and in 17%, the two conditions appeared simultaneously. The median time between the two events was 24 months. In our Italian cohort (n = 23 patients), no diagnosis of IBD was made. No significant differences were found when comparing clinical and demographical characteristics of the Italian vs. review-based cohort, except for a significant involvement of rachis in the Italian group. Conclusions: The correlation between autoinflammatory bone disease and intestinal inflammation should be further investigated. It is essential to promote awareness among pediatric rheumatologists and gastroenterologists about this possible association to facilitate the diagnosis and better optimize treatment.

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Section: Introductionmentioning

confidence: 99%

Chronic Nonbacterial Osteomyelitis and Inflammatory Bowel Disease: A Literature Review-Based Cohort

et al. 2023

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“…For the purposes of this article the term SpA was taken to include the protean manifestations associated with axial inflammation including skin and gut involvement where it has clearly been shown that IL-23 SNPs are a common denominator across the different conditions. It is also clearly evident in experimental and human systems that the IL-23/IL-17 axis is involved in skin, gut and entheseal biology ( 90 ). A differential immunopathology exists within these disease domains reflecting the context dependent biology of different tissues that is currently best understood in terms of the barrier function role of IL-17A in the gut.…”

Section: Discussionmentioning

confidence: 99%

Why Inhibition of IL-23 Lacked Efficacy in Ankylosing Spondylitis

et al. 2021

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The term spondyloarthritis pertains to both axial and peripheral arthritis including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), which is strongly linked to psoriasis and also the arthritis associated with inflammatory bowel disease. The argument supporting the role for IL-23 across the spectrum of SpA comes from 4 sources. First, genome wide associated studies (GWAS) have shown that all the aforementioned disorders exhibit IL-23R pathway SNPs, whereas HLA-B27 is not linked to all of these diseases-hence the IL-23 pathway represents the common genetic denominator. Secondly, experimental animal models have demonstrated a pivotal role for the IL-23/IL-17 axis in SpA related arthropathy that initially manifests as enthesitis, but also synovitis and axial inflammation and also associated aortic root and cutaneous inflammation. Thirdly, the emergent immunology of the human enthesis also supports the presence of IL-23 producing myeloid cells, not just at the enthesis but in other SpA associated sites including skin and gut. Finally, drugs that target the IL-23 pathway show excellent efficacy for skin disease, efficacy for IBD and also in peripheral arthropathy associated with SpA. The apparent failure of IL-23 blockade in the AS which is effectively a spinal polyenthesitis but evidence for efficacy of IL-23 inhibition for peripheral enthesitis in PsA and preliminary suggestions for benefit in axial PsA, raises many questions. Key amongst these is whether spinal inflammation may exhibit entheseal IL-17A production independent of IL-23 but peripheral enthesitis is largely dependent on IL-23 driven IL-17 production. Furthermore, IL-23 blocking strategies in animal models may prevent experimental SpA evolution but not prevent established disease, perhaps pointing towards a role for IL-23 in innate immune disease initiation whereas persistent disease is dependent on memory T-cell responses that drive IL-17A production independently of IL-23, but this needs further study. Furthermore, IL-12/23 posology in inflammatory bowel disease is substantially higher than that used in AS trials which merits consideration. Therefore, the IL-23 pathway is centrally involved in the SpA concept but the nuances and intricacies in axial inflammation that suggest non-response to IL-23 antagonism await formal definition. The absence of comparative immunology between the different skeletal sites renders explanations purely hypothetical at this juncture.

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“…Alternatively, the damage-associated molecular patterns (DAMPs) from highly biomechanically stressed entheses can disturb “fine tuning” of cytokine production in homeostatic entheseal tissues. The net-effect of these processes may serve as key drives for the onset, evolution, sustenance, flare-up, and eventual outcomes of r-AxSpA ( Sharif et al, 2020 ). The cellular and molecular bases for enthesitis in AS patients are illustrated in Figure 5 .…”

Section: Pathogenesis Of Enthesitis In As Patientsmentioning

confidence: 99%

The Potential Role of Genetics, Environmental Factors, and Gut Dysbiosis in the Aberrant Non-Coding RNA Expression to Mediate Inflammation and Osteoclastogenic/Osteogenic Differentiation in Ankylosing Spondylitis

Liao

Tsai

Lai

et al. 2022

Front. Cell Dev. Biol.

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Ankylosing spondylitis (AS) or radiographic axial spondyloarthritis is a chronic immune-mediated rheumatic disorder characterized by the inflammation in the axial skeleton, peripheral joints, and soft tissues (enthesis, fascia, and ligament). In addition, the extra-skeletal complications including anterior uveitis, interstitial lung diseases and aortitis are found. The pathogenesis of AS implicates an intricate interaction among HLA (HLA-B27) and non-HLA loci [endoplasmic reticulum aminopeptidase 1 (ERAP1), and interleukin-23 receptor (IL23R), gut dysbiosis, immune plasticity, and numerous environmental factors (infections, heavy metals, stress, cigarette smoking, etc.) The latter multiple non-genetic factors may exert a powerful stress on epigenetic regulations. These epigenetic regulations of gene expression contain DNA methylation/demethylation, histone modifications and aberrant non-coding RNAs (ncRNAs) expression, leading to inflammation and immune dysfunctions. In the present review, we shall discuss these contributory factors that are involved in AS pathogenesis, especially the aberrant ncRNA expression and its effects on the proinflammatory cytokine productions (TNF-α, IL-17 and IL-23), T cell skewing to Th1/Th17, and osteoclastogenic/osteogenic differentiation. Finally, some potential investigatory approaches are raised for solving the puzzles in AS pathogenesis.

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Intestinal and enthesis innate immunity in early axial spondyloarthropathy

Cited by 19 publications

References 83 publications

Chronic Nonbacterial Osteomyelitis and Inflammatory Bowel Disease: A Literature Review-Based Cohort

Chronic Nonbacterial Osteomyelitis and Inflammatory Bowel Disease: A Literature Review-Based Cohort

Why Inhibition of IL-23 Lacked Efficacy in Ankylosing Spondylitis

The Potential Role of Genetics, Environmental Factors, and Gut Dysbiosis in the Aberrant Non-Coding RNA Expression to Mediate Inflammation and Osteoclastogenic/Osteogenic Differentiation in Ankylosing Spondylitis

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