GIScaSpA-study of subclinical gut involvement in axial spondyloarthritis.
Ontology highlight
ABSTRACT:
SUBMITTER: Mazeda C
PROVIDER: S-EPMC10898325 | biostudies-literature | 2024
REPOSITORIES: biostudies-literature
Publications
GIScaSpA-study of subclinical gut involvement in axial spondyloarthritis.
Mazeda Carolina C Silva Susana P SP Pinto Oliveira C C Azevedo Sofia S Barcelos Anabela A
Rheumatology advances in practice 20240206 1
Similar Datasets
Project description:ObjectiveAge at onset is useful in identifying chronic back patients at an increased risk of axial SpA (axSpA). However, the majority of data on which the criterion of age at onset <45 years is based originates from Europe. Therefore it is unknown if this criterion applies in other parts of the world. We aimed to assess the age at onset of axSpA and its relationship with HLA-B27 and gender across the world.MethodsAnalyses were applied to patients from 24 countries across the world with an axSpA diagnosis and known age at onset of axial complaints. Cumulative probability plots were used to display the cumulative distribution of age at onset of axial symptoms. Linear regression models were built to assess the effect of HLA-B27 and gender on age at onset of axial symptoms.ResultsOf 2579 axSpA patients, 92% had an age at onset of axial symptoms <45 years, with only small variations across the geographical regions [Asia, n = 574 (94%); Europe and North America, n = 988 (92%); Latin America, n = 246 (89%); Middle East and North Africa, n = 771 (91%)]. Age at onset of axial symptoms was consistently lower in HLA-B27-positive patients {median 25 years [interquartile range (IQR) 19-32] vs 31 [IQR 22-39]} and male patients [median 25 years (IQR 19-33) vs 28 (IQR 21-37)], but in multivariable models an additional statistically significant effect of male gender independent of HLA-B27 was only found in Asia.ConclusionAround the world, the great majority of axSpA patients had an age at onset of axial disease of <45 years, with HLA-B27 and male gender associated with earlier disease onset.
| S-EPMC8996784 | biostudies-literature
Project description:ObjectivesDysregulation of miRNAs and their target genes contributes to the pathophysiology of autoimmune diseases. Circulating miRNAs may serve as diagnostic/prognostic biomarkers. We aimed to investigate the association between circulating miRNAs, disease activity and spinal involvement in patients with axial spondyloarthritis (AxSpA).MethodsTotal RNA was isolated from the plasma of patients with non-radiographic (nr)AxSpA, patients with ankylosing spondylitis (AS) and healthy controls (HC) via phenol-chloroform extraction. A total of 760 miRNAs were analysed with TaqMan® Low Density Arrays, and the expression of 21 miRNAs was assessed using single assays.ResultsComprehensive analysis demonstrated the differential expression of miRNAs among patients with progressive spinal disease. Of the 21 miRNAs selected according to their expression patterns, the levels of miR-625-3p were significantly different between nr-AxSpA patients and HCs. We found no correlation between miRNA levels and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in nr-AxSpA patients. Selected miRNAs, such as miR-29a-3p, miR-146a-5p or miR-222-3p with an established role in extracellular matrix formation and inflammation were associated with spinal changes and/or disease activity assessed by BASDAI in AS patients, including miR-625-3p reflecting disease activity in AS with spinal involvement.ConclusionsOur data indicate that circulating miRNAs play a role in the pathogenesis of AxSpA and are also suggestive of their potential as biomarkers of disease progression. We hypothesize that differential systemic levels of miRNA expression reflect miRNA dysregulation at sites of spinal inflammation or bone formation where these molecules contribute to the development of pathophysiological features typical of AxSpA.
| S-EPMC5609864 | biostudies-literature
Project description:Axial spondyloarthritis (AxSpA) is an inflammatory spondyloarthritis (SpA) that has significant impact on a patient's life. Symptoms, including fatigue, sleep problems, depression, and sexual dysfunction, can profoundly impact health-related quality of life (HRQoL) and limit work, leisure, and daily activities. Available therapies effectively manage pain and inflammation in early-stage disease, but patients often continue to experience impaired HRQoL. Thus, there remains a need for new therapies with novel mechanisms that can stop disease progression, potentially reverse damage caused by AxSpA and improve HRQoL in patients with AxSpA. Newer biologic agents, such as those targeting the interleukin 17-interleukin 23 axis, have promising efficacy and may improve HRQoL for patients with AxSpA. The AxSpA has many negative effects on HRQoL. By targeting disease pathways responsible for the development of AxSpA, approved and emerging therapies potentially reduce disease activity and improve the functional status of patients with AxSpA. This narrative review reflects on the findings of studies evaluating HRQoL of individuals with AxSpA and the role of newer therapies.
| S-EPMC5617559 | biostudies-other
Project description:IntroductionPatients with axial spondyloarthritis (axSpA) have a high disease burden mainly due to the rheumatic disease itself, and also exhibit accelerated atherosclerosis, that leads to a higher incidence of cardiovascular (CV) disease. Accordingly, the identification of biomarkers of CV risk and inflammation in axSpA patients is clinically relevant. In this sense, given the beneficial functions exerted by the adipomyokine irisin in processes related to CV disease and inflammation, our aim was to assess, for the first time, the role of irisin as a genetic and serological biomarker of subclinical atherosclerosis, CV risk and disease severity in axSpA patients.MethodsA large cohort of 725 Spanish patients with axSpA was included. Subclinical atherosclerosis (presence of plaques and abnormal carotid intima-media thickness values) was evaluated by carotid ultrasound. Four irisin polymorphisms (rs16835198 G/T, rs3480 A/G, rs726344 G/A, and rs1570569 G/T) were genotyped by TaqMan probes. Additionally, serum irisin levels were determined by ELISA.ResultsLow irisin levels were linked to the presence of plaques (p=0.002) and atherogenic index values ≥4 (p=0.01). Serum irisin were positively correlated with C-peptide levels (p<0.001) and negatively correlated with visual analogue scale and Bath Ankylosing Spondylitis Metrology Index (p<0.05 in all the cases). Moreover, lower irisin levels were observed in patients with sacroiliitis and in those with a negative HLA-B27 status (p<0.001 and p=0.006, respectively), as well as in those treated with non-steroidal anti-inflammatory drugs and conventional disease-modifying antirheumatic drugs (p<0.001 and p=0.002, respectively). Interestingly, the TT genotype and the T allele of rs16835198 were less frequent in axSpA patients with ASDAS >2.1 (Odds Ratio (OR): 0.48 [0.28-0.83] and OR: 0.73 [0.57-0.92], respectively, p=0.01 in both cases). Additionally, the frequency of rs1570569 T allele was higher in these patients (OR: 1.46 [1.08-1.97], p=0.01). Furthermore, the GGGT haplotype was more frequent in patients with ASDAS values >2.1 (OR: 1.73 [1.13-2.66], p=0.01).ConclusionsOur results indicate that low serum irisin levels could be indicators of the presence of subclinical atherosclerosis, high CV risk and more severe disease in axSpA patients. In addition, irisin may also constitute a genetic biomarker of disease activity in axSpA.
| S-EPMC9309281 | biostudies-literature
Project description:BackgroundBased on clinical and genetic associations, axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) are suspected to have a linked pathogenesis. Gut dysbiosis, intrinsic to IBD, has also been observed in axSpA. It is, however, not established to what degree gut dysbiosis is associated with axSpA disease severity. The objective of this study was to compare gut dysbiosis frequency between controls, non-radiographic axial spondyloarthritis (nr-axSpA), and ankylosing spondylitis (AS) patients and investigate whether gut dysbiosis is cross-sectionally associated with axSpA disease activity, physical function, mobility, or pain.MethodsGut dysbiosis was assessed by 16SrRNA analysis of feces from 44/88 nr-axSpA/AS patients (ASAS/mNY criteria) without inflammatory bowel disease (IBD) and 46 controls without IBD or rheumatic disease. The GA-map™ Dysbiosis Test was used, grading gut microbiota aberrations on a 1-5 scale, where ≥3 denotes dysbiosis. Proportions with dysbiosis were compared between the groups. Furthermore, standard axSpA measures of disease activity, function, mobility, and pain were compared between patients (nr-axSpA and AS combined) with and without dysbiosis, univariately, and adjusted for relevant confounders (ANCOVA).ResultsGut dysbiosis was more frequent in AS than controls (36% versus 17%, p=0.023), while nr-axSpA (25% dysbiosis) did not differ significantly from either AS or controls. Univariately, most axSpA measures were significantly worse in patients with dysbiosis versus those without: ASDAS-CRP between-group difference 0.6 (95% CI 0.2-0.9); BASDAI 1.6 (0.8-2.4); evaluator's global disease activity assessment (Likert scale 0-4) 0.3 (0.1-0.5), BASFI 1.5 (0.6-2.4), and VAS pain (cm) 1.3 (0.4-2.2). Differences remained significant after adjustment for demographics, lifestyle factors, treatments, gut inflammation (fecal calprotectin ≥50 mg/kg), and gut symptoms, except for VAS pain. BASMI and CRP were not associated with dysbiosis.ConclusionGut dysbiosis, more frequent in AS patients than controls, is associated with worse axSpA disease activity and physical function, seemingly irrespective of both gut inflammation and treatments. This provides further evidence for an important link between disturbances in gastrointestinal homeostasis and axSpA.
| S-EPMC8840679 | biostudies-literature
Project description:ObjectivesCurrent studies concentrate on the cytokine network and its role in the pathogenesis of spondyloarthritis (SpA). In this study, we analyzed whether the serum cytokine profile (interleukins: IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33) correlates with demographic data, clinical manifestations, disease activity and treatment outcome in a group of patients with axial spondyloarthritis.Material and methodsForty-nine patients with an established diagnosis of axial spondyloarthritis (aSpA) and 19 healthy volunteers as controls were enrolled in the study. Clinical evaluation included patient's medical history, 44 joint count, back pain intensity and global disease activity in the preceding week (VAS), the duration of morning stiffness and blood tests. Disease activity was assessed using BASDAI and ASDAS-CRP. Serum concentration of IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33 was determined.ResultsIn patients with aSpA, elevated serum concentration of IL-10, IL-15, IL-17 and IL-23 was detected. In the aSpA group we detected higher values of serum concentration of IL-23 and IL-33 in the subgroup with anterior uveitis (83.1 ±184.0 pg/ml vs. 14.0 ±17.1 pg/ml, p < 0.0001 and 45.5 ±71.9 pg/ml vs. 18.4 ±14.3 pg/ml, p < 0.0001, respectively). Additionally, in the subgroup with peripheral arthritis, elevation of serum concentration of IL-12 (249.3 ±246.9 pg/ml vs. 99.9 ±105.9 pg/ml, p = 0.0001) was detected. Patients with preradiological SpA had higher serum concentration of IL-17 than patients with established diagnosis of AS (6.37 ±8.50 pg/ml vs. 2.04 ±2.98 pg/ml, p = 0.0295). No differences in serum concentration of analyzed cytokines were found between the subgroup with low to moderate disease activity and the subgroup with high to very high disease activity.ConclusionsWe report that in aSpA patients, compared to controls, elevated serum concentrations of IL-10, IL-15, IL-17 and IL-23 were observed. Some cytokines may predispose to a more severe course of aSpA.
| S-EPMC4847310 | biostudies-literature
Project description:ObjectivesThe objective of this study is to investigate lipopolysaccharid-binding protein (LBP), zonulin and calprotectin as markers of bacterial translocation, disturbed gut barrier and intestinal inflammation in patients with radiographic axial spondyloarthritis (r-axSpA) during tumour necrosis factor inhibitor (TNFi) therapy and to analyze the association between disease activity, response to treatment and biomarker levels.MethodsPatients with active r-axSpA of the German Spondyloarthritis Inception Cohort starting TNFi were compared with controls with chronic back pain. Serum levels of LBP, zonulin and calprotectin were measured at baseline and after 1 year of TNFi therapy. We analysed the longitudinal association between biomarkers and disease activity, and the relationship between biomarkers and treatment response with regression analysis.Results121 patients with r-axSpA were compared with 63 controls. At baseline, patients with r-axSpA had higher levels of LBP and calprotectin than controls, which decreased significantly during TNFi treatment. LBP showed a positive association in longitudinal analyses with Axial Spondyloarthritis Disease Activity Score (ASDAS) (ß=0.08, 95% CI 0.06 to 0.10), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (ß=0.08, 95% CI 0.04 to 0.12) and C reactive protein (CRP) (ß=1.69, 95% CI 1.04 to 2.34). Calprotectin was associated with ASDAS (ß=0.04, 95% CI 0.01 to 0.07) and CRP (ß=0.82, 95% CI 0.27 to 1.37). Furthermore, LBP and calprotectin levels at baseline showed an association with a subsequent change in BASDAI. Baseline zonulin levels were not significantly associated with disease activity or treatment response.ConclusionSerum levels of LBP and calprotectin are associated with disease activity in patients with r-axSpA and decrease with TNFi response. In contrast, serum zonulin levels showed no association with disease activity or treatment response, arguing against a strict correlation between intestinal permeability and disease activity in axSpA.
| S-EPMC11749320 | biostudies-literature
Project description:IntroductionDiagnosis of axial spondyloarthritis (axSpA) is frequently delayed for years after symptom onset. However, little is known about patient and healthcare professional (HCP) perspectives on barriers and facilitators in axSpA diagnosis. This study explored the experiences and perceptions of both groups regarding the factors affecting the timely diagnosis of axSpA.MethodSemi-structured interviews with patients with axSpA and axSpA-interested HCPs from the United Kingdom (UK) were performed by telephone or Microsoft Teams and focussed on the individuals' perspective of the diagnostic journey for axSpA. Interview transcripts were thematically analysed.ResultsFourteen patients with axSpA (10 female, 4 male) and 14 UK based HCPs were recruited, the latter comprising of 5 physiotherapists, 4 General Practitioners, 3 rheumatologists, a nurse, and an occupational therapist. Barriers to diagnosis identified by patients and HCPs were: difficult to diagnose, a lack of awareness, unclear referral pathways, patient behaviour and patient/HCP communication. Patient-identified facilitators of diagnosis were patient advocacy, clear referral processes and pathways, increased awareness, and serendipity. HCPs identified promoting awareness as a facilitator of diagnosis, along with symptom recognition, improvements to healthcare practice and patient/HCP communications.ConclusionPoor communication and a lack of understanding of axSpA in the professional and public spheres undermine progress towards timely diagnosis of axSpA. Improving communication and awareness for patients and HCPs, along with systemic changes in healthcare (such as improved referral pathways) could reduce diagnostic delay.
| S-EPMC10980652 | biostudies-literature
Project description:ObjectivesTo explore differences in axial spondyloarthritis (axSpA) clinical phenotype around the world in a large sample of patients included in the International Map of Axial Spondyloarthritis (IMAS).MethodIMAS was a cross-sectional online survey (2017-2022) of 5557 unselected axSpA patients from 27 countries. We analysed across five geographic regions the age at symptom onset, diagnostic delay, gender, HLA-B27, family history, extra-musculoskeletal manifestations, presence of comorbidities, disease activity (BASDAI), level of spinal stiffness and treatments.ResultsOf 5557 IMAS participants, 3493 were from Europe, 770 from North America, 600 from Asia, 548 from Latin America and 146 from South Africa. Age at symptom onset ranged between 25 and 30 years and was higher in Latin America. Diagnostic delay was longest in South Africa and lowest in Asia. The lowest HLA-B27 positivity was observed in Latin America and the highest in Asia. Extra-musculoskeletal manifestations were the lowest in Europe. Mean disease activity (BASDAI) was 5.4, with highest values in South Africa and lowest in Asia. Most of the patients had used NSAIDs for their condition and less than half had ever taken conventional synthetic DMARDS; both were more frequent in Latin America and South Africa. Almost half of the patients had ever taken biologic DMARDs, more frequent use being in the Americas.ConclusionThere is great heterogeneity of axSpA clinical phenotype presentation around the world. AxSpA manifests differently in different regions, so further understanding of these differences of phenotypes is needed to achieve early diagnosis and initiation of optimal disease treatment in axSpA in the different regions.
| S-EPMC11371368 | biostudies-literature
Project description:ObjectiveTo identify the parameters associated with self-reported diagnostic delay (DD) in axial spondyloarthritis (axSpA) patients across Europe.MethodsData from 2652 patients from 13 countries who participated in the European Map of Axial Spondyloarthritis (EMAS) were collected through an online survey (2017-2018). DD was calculated as the difference between age at diagnosis and age at symptom onset reported by participants. Associations between DD and sociodemographic characteristics, as well as disease-related factors were explored through univariable and multivariable linear regression analysis.ResultsAverage DD was 7.4 (8.4) years with a variation between countries. The variables associated with longer DD in the final multivariable regression model were: younger age at symptom onset (b = -0.26; 95% CI: -0.28, -0.23), female gender (b = 1.34; 95% CI: 0.73, 1.96) and higher number of health-care professionals (HCPs) seen before diagnosis (b = 1.19; 95% CI: 0.95, 1.43). There was a significant interaction between the female gender and the number of HCPs seen before diagnosis. A substantial variation of the DD across European countries was observed.ConclusionIn this sample of axSpA patients, average DD was greater than 7 years. Younger age at symptom onset, female gender, higher number of HCPs seen before diagnosis, and being diagnosed by rheumatologist were the parameters associated with a longer DD in axSpA. These findings indicate a need for continuing efforts dedicated to recognition of patients with a high probability of axSpA on the level of non-rheumatology specialists and facilitating referral to a rheumatologist for timely diagnosis.
| S-EPMC8824419 | biostudies-literature