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  • 1
    Online Resource
    Online Resource
    In vitro triple coculture with gut microbiota from spondyloarthritis patients is characterized by inter-individual differences in inflammatory responses
    Springer Science and Business Media LLC ; 2022
    In:  Scientific Reports Vol. 12, No. 1 ( 2022-06-21)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-06-21)
    Abstract: Spondyloarthritis is a group of chronic inflammatory diseases that primarily affects axial or peripheral joints and is frequently associated with inflammation at non-articular sites. The disease is multifactorial, involving genetics, immunity and environmental factors, including the gut microbiota. In vivo , microbiome contributions are difficult to assess due to the multifactorial disease complexity. In a proof-of-concept approach, we therefore used a triple coculture model of immune-like, goblet and epithelial cells to investigate whether we could detect a differential impact from spondyloarthritis- vs. healthy-derived gut microbiota on host cell response. Despite their phylogenetic resemblance, flow cytometry-based phenotypic clustering revealed human-derived gut microbiota from healthy origin to cluster together and apart from spondyloarthritis donors. At host level, mucus production was higher upon exposure to healthy microbiota. Pro-inflammatory cytokine responses displayed more inter-individual variability in spondyloarthritis than in healthy donors. Interestingly, the high dominance in the initial sample of one patient of Prevotella , a genus previously linked to spondyloarthritis, resulted in the most differential host response upon 16 h host-microbe coincubation. While future research should further focus on inter-individual variability by using gut microbiota from a large cohort of patients, this study underscores the importance of the gut microbiota during the SpA disease course.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-022-13582-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 2
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    Spondyloarthritis: How far are we from precision medicine?
    Frontiers Media SA ; 2022
    In:  Frontiers in Medicine Vol. 9 ( 2022-9-8)
    Details
    In: Frontiers in Medicine, Frontiers Media SA, Vol. 9 ( 2022-9-8)
    Abstract: Spondyloarthritis (SpA) is a family of heterogenous diseases consisting of different phenotypes. The exact disease mechanism remains unclear but evidence shows the complex pathophysiology with interplay between genome, microbiome, and immunome. Biologic DMARDs have markedly improved patients' disease control and quality of life. However, treatment response varies among patients. There is a growing need to identify biomarkers for the diagnosis, prognosis, prevention, and treatment of SpA. Genomic studies have been the research focus in the past two decades and have identified important genes involved in SpA. In recent years, emerging evidence supports the link between gut and joint inflammation in SpA, in which the role of gut microbiome in SpA is of great interest. Herein, potential genetic and gut microbial biomarkers for predicting treatment response are discussed. Novel strategies targeting dysbiosis in SpA are also summarized. These results represent a significant step toward precision medicine for patients with SpA.
    Type of Medium: Online Resource
    ISSN: 2296-858X
    URL: Article
    DOI: 10.3389/fmed.2022.988532
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2775999-4
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  • 3
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    Monocyte transcriptomes from patients with axial spondyloarthritis reveal dysregulated monocytopoiesis and a distinct inflammatory imprint
    Springer Science and Business Media LLC ; 2021
    In:  Arthritis Research & Therapy Vol. 23, No. 1 ( 2021-12)
    Details
    In: Arthritis Research & Therapy, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2021-12)
    Abstract: In patients with axial spondyloarthritis (axSpA), monocytes show a pre-activated phenotype. Gut inflammation is a trigger of monocyte activation and may also affect their development in the bone marrow (BM). As gut inflammation is commonly observed in axSpA patients, we performed a detailed analysis of monocyte transcriptomes of axSpA patients in two cohorts and searched for signs of activation and developmental adaptations as putative imprints of gut inflammation. Methods Transcriptomes of blood CD14 + monocytes of HLA-B27+ axSpA patients and healthy controls (HC) were generated by microarrays from cohort 1 and by RNA-sequencing from cohort 2. Differentially expressed genes from both analyses were subjected to gene set enrichment analysis (GSEA) and to co-expression analysis in reference transcriptomes from BM cells, blood cells and activated monocytes. As serological markers of translocation, 1,3 beta-glycan, intestinal fatty acid binding protein, and lipopolysaccharide binding protein (LBP) were determined by LAL and ELISA. Results Transcriptome analysis identified axSpA-specific monocyte signatures showing an imprint of LPS/cytokine-activated monocytes, late granulopoietic BM cells, blood neutrophils, and G-CSF-mobilized blood cells, which suggests LPS/TNF activation and more prominent BM adaptation promoting a neutrophil-like phenotype. GSEA mapped axSpA upregulated genes to inflammatory responses and TNFα signaling and downregulated probe-sets to metabolic pathways. Among translocation markers, LBP levels were significantly increased in axSpA patients vs. HC ( p 〈 0.001). Stratified analysis by disease activity and stage identified an “active disease signature” (BASDAI ≥ 4) with an imprint of LPS/cytokine-activated monocytes and CD16 + monocyte subsets. The “AS signature” (vs. non-radiographic axSpA) showed a reinforced neutrophil-like phenotype due to deprivation of dendritic cell transcripts. Conclusions The neutrophil-like phenotype of axSpA monocytes points towards a biased monocytopoiesis from granulocyte-monocyte progenitors. This shift in monocytopoiesis and the LPS/cytokine imprint as well as the elevated LBP levels are indicators of systemic inflammation, which may result from bacterial translocation. The BM adaptation is most prominent in AS patients while disease activity appears to be linked to activation and trafficking of monocytes.
    Type of Medium: Online Resource
    ISSN: 1478-6362
    URL: Article
    DOI: 10.1186/s13075-021-02623-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041668-4
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  • 4
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    Peripheral manifestations are major determinants of disease phenotype and outcome in new onset spondyloarthritis
    Oxford University Press (OUP) ; 2022
    In:  Rheumatology Vol. 61, No. 8 ( 2022-08-03), p. 3279-3288
    Details
    In: Rheumatology, Oxford University Press (OUP), Vol. 61, No. 8 ( 2022-08-03), p. 3279-3288
    Abstract: To delineate the impact of peripheral musculoskeletal manifestations on stratification of disease phenotype and outcome in new-onset spondyloarthritis (SpA), using a prospective observational nationwide inception cohort, the BelGian Inflammatory Arthritis and spoNdylitis cohorT (Be-Giant). Methods Newly diagnosed adult SpA patients, fulfilling the Assessment of SpondyloArthritis International Society (ASAS) criteria for axial or peripheral SpA, were included in Be-Giant and prospectively followed every six months. Peripheral involvement (defined as arthritis, enthesitis and/or dactylitis) was determined in relation to clinically similar patient subsets at baseline and disease activity patterns during two-year follow-up, identified through K-means cluster analysis and latent class growth analysis. Results From November 2010 to March 2020, 367 patients were enrolled in Be-Giant, of whom 162 (44%) had peripheral manifestations. Two patient clusters [A, axial predominant (n = 248) and B, peripheral predominant (n = 119)] were identified at diagnosis. Longitudinal analysis (n = 115) revea led two trajectories of disease activity in each cluster: one with persistently high disease activity over time (‘High’), the other rapidly evolving to low disease activity (‘Low’). In cluster A patients, peripheral manifestations predisposed to the ‘High’ trajectory [odds ratio (OR) = 2.0, 95% CI: 1.3, 3.1, P = 0.001], despite more rapid initiation of biologics compared with patients without peripheral manifestations (hazard ratio (HR)  = 2.1, 95% CI: 1.0, 4.4, P = 0.04 – Cox proportional-hazards model). Conclusion Peripheral musculoskeletal manifestations are major determinants of phenotypical diversity in new-onset SpA. Intriguingly, stratification of axial SpA according to concomitant peripheral involvement identified an endotype with an unfavorable outcome despite more prompt therapeutic intensification with biologics. These observations justify an endotype-tailored approach beyond current ASAS/EULAR management recommendations.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    URL: Article
    DOI: 10.1093/rheumatology/keab887
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 5
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    Cluster analysis in early axial spondyloarthritis predicts poor outcome in the presence of peripheral articular manifestations
    Oxford University Press (OUP) ; 2022
    In:  Rheumatology Vol. 61, No. 8 ( 2022-08-03), p. 3289-3298
    Details
    In: Rheumatology, Oxford University Press (OUP), Vol. 61, No. 8 ( 2022-08-03), p. 3289-3298
    Abstract: To assess whether two cluster analysis-based axial SpA (axSpA) endotypes (A for purely axial; B for both axial and peripheral) are stable over time and are associated with different long-term disease outcomes. Methods K-means cluster analysis was performed at each visit (until 5 years) on 584 patients from the DESIR cohort, who completed all planned visits, and validated in 232 consecutive axSpA patients from the BeGiant cohort. Cluster stability overtime was assessed by kappa statistics. A generalized linear mixed-effect analysis was applied to compare outcomes between clusters. Classification and regression tree (CART) analysis was performed to determine a decision rule able to assign a given patient to a definite cluster at onset. Results Both endotypes remained remarkably stable over time. In the DESIR cohort, patients in cluster B showed higher disease activity, worse functional outcome and higher need for anti-rheumatic drugs than patients in cluster A. CART analysis yielded three main clinical features (arthritis, enthesitis and dactylitis) that accurately determined cluster assignment. These results could be replicated in the Be-GIANT cohort. Conclusion Cluster-based axSpA endotypes were reproducible in two different cohorts, stable over time and associated with different long-term outcome. The axSpA endotype with additional peripheral disease manifestations is associated with more severe disease and requires more intensive drug therapy Clinical trial registration clinicaltrials.gov, https://clinicaltrials.gov, NCT01648907.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    URL: Article
    DOI: 10.1093/rheumatology/keab873
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 6
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    Discriminative power of salivary gland ultrasound in relation to symptom-based endotypes in suspected and definite primary Sjögren's Syndrome
    Elsevier BV ; 2022
    In:  Seminars in Arthritis and Rheumatism Vol. 56 ( 2022-10), p. 152075-
    Details
    In: Seminars in Arthritis and Rheumatism, Elsevier BV, Vol. 56 ( 2022-10), p. 152075-
    Type of Medium: Online Resource
    ISSN: 0049-0172
    URL: Article
    DOI: 10.1016/j.semarthrit.2022.152075
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2048942-0
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  • 7
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    Axial involvement in patients with early peripheral spondyloarthritis: a prospective MRI study of sacroiliac joints and spine
    BMJ ; 2021
    In:  Annals of the Rheumatic Diseases Vol. 80, No. 1 ( 2021-01), p. 103-108
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. 1 ( 2021-01), p. 103-108
    Abstract: To assess axial involvement on MRI in early peripheral spondyloarthritis (pSpA) and to evaluate whether axial inflammation predicts relapse on treatment withdrawal. Methods Fifty-six patients with early, active, newly diagnosed pSpA underwent MRI of the sacroiliac joints (SIJs) and spine prior to golimumab initiation. At sustained clinical remission of pSpA, treatment was withdrawn and a second MRI was performed. Bone marrow oedema (BME) was scored by three readers according to the Spondyloarthritis Research Consortium of Canada (SPARCC) method. Scores were compared with an axial spondyloarthritis cohort (Belgian Arthritis and Spondylitis cohort). Structural lesions were assessed using a similar method. Furthermore, fulfilment of the Assessment of Spondyloarthritis International Society (ASAS) definition of a positive MRI for sacroiliitis was assessed. Spinal images were evaluated for BME and structural lesions using the Canada-Denmark MRI spine scoring system by two readers. Results Thirty-six per cent showed SIJ BME at baseline, all fulfilling the ASAS definition of sacroiliitis. No association with back pain was found. Twenty-one per cent displayed SIJ structural lesions. Spinal BME was limited: the median inflammation scores were low and no patients had ≥5 inflammatory corner lesions. On clinical remission, a significant decrease in SIJ SPARCC scores was detected. On clinical remission, no significant differences in SIJ SPARCC scores were noted between patients relapsing and those maintaining remission after treatment discontinuation. Conclusion In patients with early pSpA, a surprisingly high prevalence of sacroiliitis on MRI was observed; SPARCC scores decreased significantly on tumour necrosis factor inhibition. Residual inflammation on MRI was not predictive of relapse of peripheral manifestations. No relevant inflammatory spinal involvement was detected. Collectively, our findings suggest a higher inflammatory burden in patients with early pSpA than anticipated.
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2020-218480
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 1481557-6
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  • 8
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    High prevalence of spondyloarthritis-like MRI lesions in postpartum women: a prospective analysis in relation to maternal, child and birth characteristics
    BMJ ; 2020
    In:  Annals of the Rheumatic Diseases Vol. 79, No. 7 ( 2020-07), p. 929-934
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. 7 ( 2020-07), p. 929-934
    Abstract: Bone marrow oedema (BMO) on MRI of sacroiliac joints (SIJs) represents a hallmark of axial spondyloarthritis (SpA), yet such lesions may also occur under augmented mechanical stress in healthy subjects. We therefore sought to delineate the relationship between pregnancy/delivery and pelvic stress through a prospective study with repeated MRI. Results were matched with maternal, child and birth characteristics. Methods Thirty-five women underwent a baseline MRI-SIJ within the first 10 days after giving birth. MRI was repeated after 6 months and, if positive for sacroiliitis according to the Assessment of SpondyloArthritis International Society (ASAS) definition, after 12 months. BMO and structural lesions were scored by three trained readers using the Spondyloarthritis Research Consortium of Canada (SPARCC) method. Results Seventy-seven per cent of the subjects (27/35) displayed sacroiliac BMO immediately postpartum, 60% fulfilled the ASAS definition of a positive MRI. After 6 months, 46% of the subjects (15/33) still showed BMO, representing 15% (5/33) with a positive MRI. After 12 months, MRI was still positive in 12% of the subjects (4/33). Few structural lesions were detected. Intriguingly, in this study, the presence of BMO was related to a shorter duration of labour and lack of epidural anaesthesia. Conclusion A surprisingly high prevalence of sacroiliac BMO occurs in women immediately postpartum. Our data reveal a need for a waiting period of at least 6 months to perform an MRI-SIJ in postpartum women with back pain. This study also underscores the importance of interpreting MRI-SIJ findings in the appropriate clinical context.
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2020-217095
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1481557-6
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  • 9
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    Unexpected impact of COVID-19 lockdown on spinal mobility and health perception in spondyloarthritis
    BMJ ; 2021
    In:  Annals of the Rheumatic Diseases Vol. 80, No. 12 ( 2021-12), p. 1638-1640
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. 12 ( 2021-12), p. 1638-1640
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2021-220584
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 1481557-6
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  • 10
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    Anti-CD74 IgA antibodies show diagnostic potential for axial spondyloarthritis but are not associated with microscopic gut inflammation
    Oxford University Press (OUP) ; 2023
    In:  Rheumatology Vol. 62, No. 2 ( 2023-02-01), p. 984-990
    Details
    In: Rheumatology, Oxford University Press (OUP), Vol. 62, No. 2 ( 2023-02-01), p. 984-990
    Abstract: Gut inflammation commonly occurs in axial SpA (axSpA), and is linked to disease activity and outcome. Given the role of IgA in mucosal immunity, we explored the association between anti-CD74 IgA antibodies, gut inflammation and axSpA. Methods Anti-CD74 IgA was measured by ELISA in serum samples of axSpA patients, fulfilling the 2009 Assessment of SpondyloArthritis international Society classification criteria. A group of fibromyalgia (FM) and RA patients served as non-inflammatory and inflammatory controls. Newly diagnosed axSpA patients underwent ileocolonoscopy; mucosal biopsies were histopathologically assessed as normal, acute or chronically inflamed. Optimal anti-CD74 IgA cut-off values were determined with a receiver operating characteristics curve. Results axSpA patients (n = 281) showed higher anti-CD74 IgA levels [mean (s.d.) 18.8 (12.4) U/ml] compared with 100 FM patients [10.9 (5.0) U/ml, P  & lt; 0.001] and 34 RA patients [13.7 (9.6) U/ml, P = 0.02] . The area under the receiver operating characteristics curve for diagnosis (axSpA vs FM) was 0.70, providing a sensitivity of 60% and specificity of 87% (cut-off 15 U/ml). Antibody concentrations were not significantly different between axSpA patients with (n = 40) and without (n = 69) gut inflammation (P = 0.83), yielding an area under the receiver operating characteristics curve of 0.51. Anti-CD74 IgA levels were not associated with degree of bone marrow oedema on MRI of the sacroiliac joints, CRP or any other disease-specific feature such as the use of NSAIDs or biological treatment. Conclusion Serum anti-CD74 IgA is a potentially useful diagnostic biomarker for axSpA. However, antibody levels do not correlate with any phenotypical feature, including microscopic gut inflammation, suggesting this to be a disease-specific rather than an inflammatory marker.
    Type of Medium: Online Resource
    ISSN: 1462-0324 , 1462-0332
    URL: Article
    DOI: 10.1093/rheumatology/keac384
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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