Nejvíce citovaný článek - PubMed ID 19248087
Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that affects the spine and sacroiliac joints. Early detection of axSpA is crucial to slow disease progression and maintain remission or low disease activity. However, current biomarkers are insufficient for diagnosing axSpA or distinguishing between its radiographic (r-axSpA) and non-radiographic (nr-axSpA) subsets. To address this, we conducted a study using miRNA profiling with massive parallel sequencing (MPS) and SmartChip qRT-PCR validation. The goal was to identify differentially expressed miRNAs in axSpA patients, specifically those subdiagnosed with nr-axSpA or r-axSpA. Disease activity was measured using C-reactive protein (CRP) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Radiographic assessments of the cervical and lumbar spine were performed at baseline and after two years. Out of the initial 432 miRNAs, 90 met the selection criteria, and 45 were validated out of which miR-1-3p was upregulated, whereas miR-1248 and miR-1246 were downregulated in axSpA patients. The expression of miR-1-3p correlated with interleukin (IL)-17 and tumour necrosis factor (TNF) levels, indicating its significant role in axSpA pathogenesis. Although specific miRNAs distinguishing disease subtypes or correlating with disease activity or spinal changes were not found, the study identified three dysregulated miRNAs in axSpA patients, with miR-1-3p linked to IL-17 and TNF, underscoring its pathogenetic significance. These findings could help improve the early detection and treatment of axSpA.
- Klíčová slova
- Axial spondyloarthritis, Biomarkers, Cytokines, Profiling, miRNA,
- Publikační typ
- časopisecké články MeSH
Local inflammation in axial spondyloarthritis (axSpA) leads to the release of collagen metabolites from the disease-affected tissue. We investigated whether collagen metabolites were associated with disease activity and could distinguish non-radiographic(nr)-axSpA from ankylosing spondylitis (AS). A total of 193 axSpA patients (nr-axSpA, n = 121 and AS, n = 72) and asymptomatic controls (n = 100) were included. Serum levels of metalloproteinase (MMP)-degraded collagen type I (C1M), type II (C2M), type III (C3M) and type IV (C4M2) were quantified by enzyme-linked immunosorbent assay (ELISA). All metabolites were higher in axSpA than in controls (all p < 0.001). Serum levels of C1M, C3M, and C4M2 were increased in AS compared to nr-axSpA (43.4 ng/mL vs. 34.6; p < 0.001, 15.4 vs. 12.8; p = 0.001, and 27.8 vs. 22.4; p < 0.001). The best metabolite to differentiate between axSpA and controls was C3M (AUC 0.95; specificity 92.0, sensitivity 83.4). C1M correlated with ASDAS-CRP in nr-axSpA (ρ = 0.37; p < 0.001) and AS (ρ = 0.57; p < 0.001). C1M, C3M, and C4M2 were associated with ASDAS-CRP in AS and nr-axSpA after adjustment for age, gender, and disease duration. Serum levels of collagen metabolites were significantly higher in AS and nr-axSpA than in controls. Moreover, the present study indicates that collagen metabolites reflect disease activity and are useful biomarkers of axSpA.
- MeSH
- ankylózující spondylitida krev diagnóza MeSH
- biologické markery krev MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- fibrilární kolageny metabolismus MeSH
- kolagen typ II metabolismus MeSH
- kolagen typ III metabolismus MeSH
- kolagen typu I metabolismus MeSH
- kolagen typu IV metabolismus MeSH
- lidé MeSH
- spondylartritida krev diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- fibrilární kolageny MeSH
- kolagen typ II MeSH
- kolagen typ III MeSH
- kolagen typu I MeSH
- kolagen typu IV MeSH
OBJECTIVE: This study compared demographic, clinical and laboratory characteristics between patients with radiographic and non-radiographic axial spondyloarthritis (axSpA). METHODS: In this single-centre cross-sectional study, a total of 246 patients with axSpA fulfilling the imaging arm of Assessment of SpondyloArthritis International Society classification criteria were recruited. A total of 140 patients were diagnosed as non-radiographic axial spondyloarthritis (nr-axSpA), and 106 patients had ankylosing spondylitis (AS). Sociodemographic characteristics, disease manifestations, clinical and laboratory disease activity and their differences between subsets were analysed. P values below 0.05 with CI 95% were considered statistically significant. RESULTS: More nr-axSpA patients were women (61.4%) compared with 24.7% of AS patients. First symptoms developed earlier in AS patients compared with nr-axSpA (23.0 (IQR 17.5-30.0) vs 27.8 (IQR 21.0-33.7) years, p=0.001). Disease manifestations did not differ, but patients with nr-axSpA experienced peripheral arthritis more frequently (35.7% vs 17.0%, p=0.001) with less hip involvement (8.6% vs 18.9%, p=0.022) compared with patients with AS. Patients with AS exhibited worse spinal mobility and physical function compared with nr-axSpA. AS Disease Activity Scores and CRP levels were significantly higher in patients with AS compared with nr-axSpA (2.4 (IQR 1.7-2.8) vs 2.0 (IQR 1.1-2.3), p=0.022 and 7.1 (IQR 2.6-14.9) vs 2.5 (IQR 0.8-8.2) mg/L, p<0.001, respectively). CONCLUSIONS: Our data demonstrated some known and also novel differences between the two imaging arm fulfilling axSpA subgroups. Non-radiographic patients were mostly women who had experienced shorter disease duration, milder disease activity and better functional status with less hip involvement but more peripheral arthritis compared with patients with AS.
- Klíčová slova
- ankylosing spondylitis, disease activity, non-radiographic axial spondyloarthritis, spondyloarthritis,
- MeSH
- ankylózující spondylitida diagnóza epidemiologie patologie MeSH
- C-reaktivní protein metabolismus MeSH
- dospělí MeSH
- kohortové studie MeSH
- lidé MeSH
- páteř patologie MeSH
- prevalence MeSH
- průřezové studie MeSH
- radiografie MeSH
- rozsah kloubních pohybů MeSH
- sexuální faktory MeSH
- společnosti lékařské MeSH
- spondylartritida klasifikace diagnóza epidemiologie patologie MeSH
- stupeň závažnosti nemoci * MeSH
- tělesná a funkční výkonnost MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- C-reaktivní protein MeSH
The objective of this study was to investigate the patient-reported outcomes (PROs) and matrix metalloproteinase (MMP) derived extracellular matrix (ECM) biomarkers in non-radiographic (nr)-axial spondyloarthritis (axSpA) and radiographic (r)-axSpA after exercise intervention. Forty-six axSpA patients with stable disease and treatment underwent 24 weeks long exercise intervention. The clinical and laboratory assessments were performed at baseline and at follow-up. The PROs included evaluation of patient's global disease activity (PGDA), disease activity (DA7), pain (PAIN7) and fatigue during last week and quality of life questionnaires. ELISAs for MMP-degraded collagen type II, C-reactive protein (CRPM) and citrullinated vimentin were used. The data of 23 r-axSpA and 19 nr-axSpA were analysed. The PDGA was similar for nr-axSpA (35.2 ± 18.9) and r-axSpA (33.4 ± 22.3) at baseline, improved significantly after intervention (p < 0.01) and the change of PDGA was almost identical for nr-axSpA (- 10.0 ± 15.4) and r-axSpA (- 9.8 ± 11.9). Evaluations of DA7 and PAIN7 were significantly improved only in nr-axSpA (3.5 ± 2.3 and 34.7 ± 25.6 at baseline vs. 2.1 ± 1.9 and 21.0 ± 20.5, respectively, p < 0.01). The decline of DA7 and PAIN7 was more profound, but not significantly in nr-axSpA than in r-axSpA (- 1.4 ± 1.6 and - 13.7 ± 17.4 vs. - 0.5 ± 3.1 and - 3.7 ± 3.3, respectively). The quality of life was not changed. At baseline, increased levels of CRPM were found in r-axSpA (14.85 ± 4.10) compared to nr-axSpA (11.83 ± 3.20), p < 0.05, but all three biomarkers were not influenced by exercise therapy. We found that exercise therapy mainly in the nr-axSpA improves PROs, but not ECM turnover biomarkers. This indicates that exercise therapy is important for patients' health but does not affect ECM turnover.
- Klíčová slova
- axial spondyloarthritis, exercise therapy, extracellular matrix, matrix metalloproteinase,
- MeSH
- biologické markery analýza MeSH
- C-reaktivní protein analýza MeSH
- dospělí MeSH
- hodnocení výsledků péče pacientem * MeSH
- kvalita života MeSH
- lidé MeSH
- matrixové metaloproteinasy analýza MeSH
- peptidové mapování MeSH
- spondylartritida rehabilitace MeSH
- terapie cvičením * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- C-reaktivní protein MeSH
- matrixové metaloproteinasy MeSH
BACKGROUND: The efficacy of exercise therapy for ankylosing spondylitis (AS) is well-documented, but dearth of information is for non-radiographic axial spondyloarthritis (nr-axSpA). Biomarkers like serum calprotectin, interleukins IL-6, IL-17 and tumour necrosis factor (TNF)-α may reflect the disease activity of axial spondyloarthritis (axSpA). In this study, we investigated clinical and laboratory parameters of both axSpA subgroups in response to intensive physical exercise. METHODS: Altogether, 46 patients with axSpA, characterised according to the Assessment of SpondyloArthritis International Society criteria as having nr-axSpA or AS underwent 6-month exercise programme. Clinical outcomes of disease activity, Bath AS Disease Activity Index (BASDAI), AS Disease Activity Index (ASDAS-CRP), mobility, Bath AS Metrology Index (BASMI) and function, Bath AS Functional Index (BASFI) were evaluated at baseline and at the end of the exercise programme. Serum IL-6 and IL-17, TNF-α and calprotectin were measured via ELISA. The clinical and laboratory data of 29 control axSpA patients were used for the evaluation of the results. RESULTS: In all axSpA patients, the ASDAS-CRP (2.10 ± 0.12 to 1.84 ± 0.11, p <0.01) and BASMI (1.28 ± 0.14 to 0.66 ± 0.84, p <0.0001) improved after 6 months of exercise therapy. There was a significant improvement in the ASDAS-CRP in the nr-axSpA subgroup (2.01 ± 0.19 to 1.73 ± 0.16, p <0.05) and in the BASMI in both, the nr-axSpA and the AS subgroups (1.09 ± 0.12 to 0.47 ± 0.08, p <0.0001 and 1.43 ± 0.24 to 0.82 ± 0.23, p <0.0001, respectively). Both, ASDAS-CRP and BASDAI, were significantly improved in the exercise axSpA group compared to the control axSpA group (mean -0.26 vs. -0.13 and -0.49 vs. 0.12, respectively, all p <0.05). Only calprotectin was significantly reduced after the exercise programme in nr-axSpA and AS patients (from 2379.0 ± 243.20 to 1779.0 ± 138.30 μg/mL and from 2430.0 ± 269.70 to 1816.0 ± 148.20 μg/mL, respectively, all p <0.01). The change in calprotectin was more profound in the axSpA intervention group (mean -604.56) than in the control axSpA (mean -149.28, p <0.05). CONCLUSION: This study demonstrated similar efficacy for an intensive exercise programme in both nr-axSpA and AS patients. A significant decrease in serum calprotectin levels in both subgroups of axSpA patients after the exercise programme reflected an improvement in the disease activity and spinal mobility.
- Klíčová slova
- Ankylosing spondylitis, Axial spondyloarthritis, Calprotectin, Disease activity, Exercise programme, Non-radiographic,
- MeSH
- ankylózující spondylitida krev rehabilitace MeSH
- biologické markery krev MeSH
- dospělí MeSH
- ELISA MeSH
- imunoanalýza MeSH
- leukocytární L1-antigenní komplex krev MeSH
- lidé MeSH
- spondylartritida krev rehabilitace MeSH
- terapie cvičením metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- leukocytární L1-antigenní komplex MeSH