scholarly journals Serum Sclerostin as a Possible Biomarker in Ankylosing Spondylitis: A Case-Control Study

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Fabio Massimo Perrotta ◽  
Fulvia Ceccarelli ◽  
Cristiana Barbati ◽  
Tania Colasanti ◽  
Antonia De Socio ◽  
...  

Objective. Several molecules are involved in the pathogenesis of a new bone formation in ankylosing spondylitis (AS). The aim of this study was to evaluate the serum levels of sclerostin in patients with AS as a possible biomarker and to investigate any correlations with radiographic damage, disease activity, and function. Methods. AS patients fulfilled the modified New York criteria, and healthy controls were enrolled for this study. BASDAI, ASDAS-CRP, BASMI, BASFI, patient and physician VAS, and C-reactive protein were evaluated at baseline visit. Spinal damage was assessed using the mSASSS on radiographs performed within 3 months from baseline. Serum concentrations of sclerostin were assessed at baseline and after four months of therapy in patients who started an anti-TNF. Results. Twenty healthy subjects and 40 AS patients were enrolled in the study. In our group, serum sclerostin levels (median (25th–75th percentile)) were significantly higher in healthy controls (18.04 (13.6–24) pg/ml) than in AS patients (6.46 (4.5–11.1) pg/ml; P value < 0.01). However, no significant correlations were found between serum sclerostin levels and radiographic damage, assessed by mSASSS, and between serum sclerostin levels and clinical indices of activity and disability or with laboratory parameters. Sclerostin levels did not show significant changes after 4 months of anti-TNF therapy. Conclusions. The results of our study suggest a possible role of sclerostin in the identification of AS patients. Further studies are needed to prove the role of sclerostin as a disease activity biomarker and progression of disease in AS.

2010 ◽  
Vol 37 (4) ◽  
pp. 829-834 ◽  
Author(s):  
TAMAR F. BRIONEZ ◽  
SHERVIN ASSASSI ◽  
JOHN D. REVEILLE ◽  
CHARLES GREEN ◽  
THOMAS LEARCH ◽  
...  

Objective.To investigate the role of psychological variables in self-reported disease activity in patients with ankylosing spondylitis (AS), while controlling for demographic and medical variables.Methods.Patients with AS (n = 294) meeting modified New York criteria completed psychological measures evaluating depression, resilience, active and passive coping, internality, and helplessness. Demographic, clinical, and radiologic data were also collected. Univariate and multivariate analyses were completed to determine the strength of the correlation of psychological variables with disease activity, as measured by the Bath AS Disease Activity Index (BASDAI).Results.In the multivariate regression analysis, the psychological variables contributed significantly to the variance in BASDAI scores, adding an additional 33% to the overall R-square beyond that accounted for by demographic and medical variables (combined R-square 18%). Specifically, arthritis helplessness and depression accounted for the most significant portion of the variance in BASDAI scores in the final model.Conclusion.Arthritis helplessness and depression accounted for significant variability in self-reported disease activity beyond clinical and demographic variables in patients with AS. These findings have important clinical implications in the treatment and monitoring of disease activity in AS, and suggest potential avenues of intervention.


Lupus ◽  
2011 ◽  
Vol 20 (14) ◽  
pp. 1494-1500 ◽  
Author(s):  
Z Rezaieyazdi ◽  
M Sahebari ◽  
MR Hatef ◽  
B Abbasi ◽  
H Rafatpanah ◽  
...  

The role of C-reactive protein (CRP) in systemic lupus erythematosus (SLE) as an inflammatory marker is still controversial. Recently, more sensitive methods, such as high sensitive CRP (hs-CRP) have been used to detect micro-inflammation. The role of hs-CRP in lupus flare has not been documented well. We conducted this study to examine the correlation between hs-CRP serum concentrations and disease activity in lupus. Ninety-two SLE patients and 49 healthy controls contributed to our study. Most confounding factors influencing the hs-CRP values were excluded. Disease activity was estimated using the SLE Disease Activity Index (SLEDAI-2K). hs-CRP values were determined using an enzyme-linked immunosorbent assay (ELISA) kit. Serum values of hs-CRP were significantly higher ( p < 0.001, z = 3.29) in patients compared with healthy controls. The cutoff point for hs-CRP between patients and controls was 0.93 mg/L (Youden’s Index = 0.39). There was no correlation between hs-CRP serum levels and disease activity. Furthermore, hs-CRP values did not correlate with any of the laboratory parameters, except for C3 ( p = 0.003, rs = −0.2) and C4 ( p = 0.02, rs = −0.1). Although hs-CRP serum levels were significantly higher in lupus patients compared with healthy controls, it seems that this marker is not a good indicator for disease activity.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 884.1-885
Author(s):  
E. Aleksandrova ◽  
A. Novikov ◽  
P. Kulakova ◽  
A. Dorofeev ◽  
N. Savenkova ◽  
...  

Background:Ankylosing spondylitis (AS) is a chronic inflammatory disease of the spine and sacroiliac joints characterized by new bone formation (syndesmophytes) and ankyloses. In AS cases, along with the damage to the musculoskeletal system, impairment of other organs and systems is often observed (uveitis, inflammatory bowel and heart diseases). Pro-inflammatory cytokines (TNF-α, IL-6,-17,-23,-21,-22,-31) and chemokines (IL-8) are key pathogenic markers in AS.Objectives:The aims of the study were to determine the serum levels of IL-6 and IL-8 in AS and investigate their relationship with disease activity.Methods:We studied 140 patients (pts) with AS fulfilled modified New York criteria (1984); (102M/38F); median and interquartile range (25th—75th percentile) of age 43.0; 35.0-51.0 years; disease duration 6.0; 4.0-12.0 years; BASDAI - 5.4; 4.1-6.6; ASDAS ESR - 3.6; 2.6-4.4; ASDAS CRP - 3.8; 2.7-4.5; 86% HLA-27 positive. In 50% of pts with AS, inflammatory bowel diseases (IBD) (Crohn’s disease and ulcerative colitis) were diagnosed. The control group included 17 healthy donors (HC). The serum concentrations of IL-6 and IL-8 were detected by chemiluminescence immunoassay using IMMULATE 1000 analyzer (Siemens Healthcare Diagnostics, USA).Results:AS pts had significantly higher serum level of IL-6 than HC (4.3; 0.1-8.0 pg/ml vs 2.3; 0.1-2.7 pg/ml, p <0.006). The median concentration of IL-8 didn’t differ between AS pts and HC (10.5; 8.3-18.0 pg/ml vs 11.9; 8.2-18.3 pg/ml, p>0.05). The same levels of IL-6 and IL-8 were detected in AS with IBD and AS without signs of IBD (p>0.05). In AS pts, serum IL-6 concentration was positively correlated with ASDAS ESR (r = 0.3), ASDAS CRP (r = 0.3), ESR (r = 0.3) and CRP (r = 0.5) (p <0.05); IL-8 was negatively associated with presence of fecal calprotectin (r = -0.3) (p <0.05).Conclusion:Elevated serum concentration of IL-6 in AS is associated with clinical and laboratory markers of high inflammatory activity of the disease. The levels of IL-8 in the sera of AS patients were negatively correlated with the concentration of fecal calprotectin. Data on the relationship of IL-8 with the activity of the pathological process in AS require further study.Disclosure of Interests:Elena Aleksandrova: None declared, Alexander Novikov: None declared, Polina Kulakova: None declared, Aleksey Dorofeev: None declared, Nadezhda Savenkova: None declared, Evgeniy Volnukhin: None declared, Anton Kovshik: None declared, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche


2020 ◽  
Author(s):  
Jing Wang ◽  
Yuan Yuan ◽  
Xiaxia Jin ◽  
Guoguang Lu

Abstract Background: Ankylosing spondylitis (AS)is a chronic inflammatory disorder involving the sacroiliac joints, lumbar spine, thoracic spine and even cervical spine, and could leading to disability due to the failure of timely treatment. Therefore, early diagnosis is essential to for AS treatment. The lymphocyte-monocyte ratio (LMR) is a systemic inflammatory and immunological indicator for prediction of disease development and progression. However, its role in AS remains unclear. The aim of this study was to investigate the role of LMR in AS diagnosis, disease activity classification and sacroiliac arthritis staging. Methods: Seventy-eight AS patients and 78 sex-age-matched healthy controls (HCs) were enrolled in this study. The diagnosis of AS was performed according to the New York criteria, whereas the staging of sacroiliac arthritis of AS patients was determined by X-ray examination.Comparison of between AS patients and HCs and between patients with high and low stages on LMR levels and other laboratory indicators were carried out. Results: A higher level of NLR, RDW, PLR, MPV, ESR, CRP and lower level of RBC, Hb, Hct, LMR, ALT, AST, TBIL and A/G were noted in the AS patients compared to HCs. A positive correlation was observed between LMR and RBC, Hb, Hct and A/G, while negative correlation was found between LMR and NLR, PLR, AST, TBIL (P< 0.05). The ROC curve showed that the area under the curve of LMR was 0.803(95%CI =0.734-0.872), with a sensitivity and specificity of 62.8% and 87.2%,and the AUC (95%CI) for ESR, CRP and LMR in the combined diagnosis of ankylosing spondylitis were 0.975(0.948-1.000),with the sensitivity and specificity of 94.9% and 97.4% .Levels of WBC and NLR were higher in high X-ray stage patients, whereas levels of LMR was lower (P<0.05) and statistical differences were observed of LMR values among different stages (P<0.05). Conclusions: Our study suggested that LMR is an important inflammatory marker that can be used to diagnosis AS and identify disease activity and X-ray stage of sacroiliac arthritis in AS patients.


2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Victoria Furer ◽  
Eyal Hazan ◽  
Adi Mor ◽  
Michal Segal ◽  
Avi Katav ◽  
...  

FMS patients demonstrate an altered profile of chemokines relative to healthy controls (HC). Eotaxin-2 is a potent chemoattractant distributed in a variety of tissues. The aim of the study was to compare serum levels of eotaxin-2 between FMS patients and HC and to examine a potential correlation between eotaxin-2 levels and clinical parameters of FMS. Methods. 50 patients with FMS and 15 HC were recruited. Data on the severity of FMS symptoms and depression were collected. Serum levels of eotaxin-2 (ELISA) were determined in all participants. High-sensitive CRP (hs-CRP) was measured in the FMS group. Results. The FMS cohort included predominantly females (84%), mean age of 49, and mean disease duration of 6 years. FMS patients exhibited significantly higher eotaxin-2 levels (pg/ml) versus HC: 833 (±384) versus 622 (±149), p=0.04. Mean hs-CRP level among FMS patients was 4.8 ± 6 mg/l, a value not indicative of acute inflammation. No correlation was found between eotaxin-2 and hs-CRP levels. No correlation was found between eotaxin-2 and severity measures of FMS or depression. Conclusion. Eotaxin-2 does not appear to be a candidate for a disease activity biomarker in FMS. Further research is warranted into the role of this chemokine in the pathophysiology of the FMS.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 156.1-156
Author(s):  
E. Zaccagnino ◽  
R. Patel ◽  
L. S. Gensler

Background:Axial Spondyloarthritis (axSpA) is a chronic inflammatory disease affecting the axial skeleton. It includes non-radiographic axSpA and radiographic axSpA [Ankylosing Spondylitis (AS)]. Male axSpA patients often have greater damage, while women report a higher disease burden. The role of pelvic morphology in the axSpA phenotype has not been explored. There is anatomic sexual dimorphism between the male and female pelvis. Given the phenotypic gender differences in axSpA, the role of pelvic morphometry is of interest.Objectives:The purpose of this study is to determine whether an association exists between pelvic dimensions and radiographic damage in patients with axSpA, as well as to compare these measurements in axSpA patients and healthy controls.Methods:This was a cross-sectional analysis comparing axSpA cases from a prospective cohort and non-axSpA controls from the UCSF radiology databank. Informed consent was obtained from axSpA cohort patients and this study was approved by the institutional IRB. To be included in the analysis, we limited inclusion to age ≤ 50 with an Anterior Posterior (AP) pelvis radiograph in the system. We excluded non-nulliparity, pelvic fracture history, BMI ≥ 30kg/m2, any prosthetic history and avascular necrosis. We measured the pelvic inlet, pelvic outlet, and subpubic angle (based on validated scoring methods) (Figure 1) and assessed its relation to sacroiliac joint (SIJ) damage (average SIJ score, New York criteria) and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) in cases. AxSpA patients were also compared to age/gender matched controls. Pelvic measurements were performed by 2 blinded independent-trained readers in randomized, blinded image order. Inter-rater reliability was assessed. When examining the relationship between pelvic measurements and damage, linear regression was used to stratify by gender and adjust for potential confounders.Results:The axSpA cohort included 481 patients, of which 210 men and 89 women were included in this analysis and gender/age matched controls. Rater inter-class correlation was above 0.70 for pelvic outlet and above 0.80 for other measures. Cases and controls were similar (Table 1). The regression analysis showed a significant relationship between the sub-pubic angle and damage in the spine (coeff=-0.342, p=0.003) in men with axSpA. A sensitivity analysis, excluding mSASSS outliers (mSASSS ≥ 16) upheld the relationship (coeff=-1.40, p=0.002).Conclusion:In men with axSpA, there appears to be a relationship between sub-pubic angle and spinal radiographic damage. This is consistent with our finding that women have larger sub-pubic angles and lower spinal radiographic damage than men. A greater sub-pubic angle may protect against spinal involvement or associate with other protective factors. Further work should be performed to understand the contribution of pelvic anatomy to damage in axSpA.Disclosure of Interests:Ethan Zaccagnino: None declared, Rina Patel: None declared, Lianne S. Gensler Consultant of: AbbVie, Eli Lilly, Gilead, Novartis, Pfizer and UCB., Grant/research support from: Pfizer and UCB.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1356.1-1356
Author(s):  
J. Zhao ◽  
X. Ye ◽  
Z. Zhang

Background:Syndecan-4, one of the members of heparan sulphate proteoglycans (HSPGs), has been shown to be involved in regulating inflammatory responses, angiogenesis, and cell migration. Its role has been proved in animal arthritis models, however not clearly elucidated in rheumatoid arthritis (RA) patientsObjectives:To investigate the role of Syndecan-4 in the pathogenesis of RA, by detecting Syndecan-4 expression in the serum, synovial fluid and synovium of RA patients and comparing with osteoarthritis (OA) patientsMethods:The concentrations of syndecan-4 in sera and synovial fluid of RA and osteoarthritis (OA) patients were detected by ELISA. The expression of syndecan-4 in synovium of RA and OA patients was detected by immunohistochemistry. In another cohort of 60 RA patients, the association analysis was performed. All the RA patients were with disease duration more than 6 months and with DAS28-CRP>3.2 although after csDMARDs (including MTX and/or leflunomide) treatment for more than 3 months. The RA patients were treated with tumour necrosis factor α (TNFα) inhibitor (TNFi) and MTX 10mg per week for 12 weeks. The correlations between sera Syndecan-4 and disease activity of RA as well as therapeutic response to TNFi were analyzed.Results:The serum Syndedcan-4 level of RA patients [637.1 (483.6-1069.6) pg/mL] was significantly higher than that of OA patients [345.0 (287.9-421.1) pg/mL] and healthy controls [195.6 (165.0-225.2) pg/mL](P<0.001, P<0.001, respectively). The serum concentration of Syndecan-4 is also higher in OA patients than that in healthy controls (P<0.001). It was also higher in RF-positive RA patients than in RF-negative ones [603.0 (100.0-8879.1) pg/mL vs 460.3 (178.7-2468.9) pg/mL, (p=0.026)]. The Syndedcan-4 level in synovial fluid and synovia were comparable between RA and OA patients. No correlation was found between serum Syndedcan-4 and disease activity of RA. TNFi treatment did not change the serum Syndecan-4 level significantly. The baseline serum Syndecan-4 did not show predictive value for TNFi response.Conclusion:Syndecan-4 can be expressed in the synovia of RA and OA patients. The serum Syndecan-4 is higher in RA patients than in OA patients and healthy controls, and significantly higher in sero-positive RA patients than in sero-negative ones. Syndecan-4 may participate in the pathogenesis of RA.References:[1]Leonova EI, Galzitskaya OV. Role of Syndecans in Lipid Metabolism and Human Diseases. Adv Exp Med Biol, 2015, 855: 241-58.[2]Xie J, Wang J, Li R, Dai Q, Yong Y, Zong B, et al. Syndecan-4 over-expression preserves cardiac function in a rat model of myocardial infarction. J Mol Cell Cardiol 2012; 53: 250-8.[3]Strand ME, Aronsen JM, Braathen B, Sjaastad I, Kvaløy H, Tønnessen T, et al. Shedding of syndecan-4 promotes immune cell recruitment and mitigates cardiac dysfunction after lipopolysaccharide challenge in mice. J Mol Cell Cardiol. 2015;88:133-44.[4]Endo T, Ito K, Morimoto J, Kanayama M, Ota D, Ikesue M, et al. Syndecan 4 Regulation of the Development of Autoimmune Arthritis in Mice by Modulating B Cell Migration and Germinal Center Formation. Arthritis Rheumatol. 2015; 67:2512-22.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1656.1-1656
Author(s):  
I. Shynkaruk ◽  
O. Iaremenko ◽  
D. Fedkov ◽  
K. Iaremenko ◽  
K. Mazanko

Background:There is an actual demand for searching the biomarkers which could reflect disease activity and MRI changes in sacroiliac joints (SIJ) and spine in patients with spondyloarthritis (SpA). Transforming growth factor-beta 1 (TGF-β1) is a cytokine that suppresses inflammatory cytokines but could augment inflammation [1]. A very recent study suggests a possible role of sclerostin (Scl) in the identification of SpA patients, but further studies are needed to prove its role as a disease activity and progression biomarker [2]. In general, the role of these biomarkers in SpA patients remains unknown due to controversial data about their levels in patients with SpA in comparison with healthy subjects and correlations with SpA activity.Objectives:This study was designed to determine TGF-β1 and Scl serum levels and its correlations with changes in spine and SIJ on MRI imaging, laboratory parameters and indices of disease activity and functional status in SpA patients.Methods:102 patients with SpA (mean age (M±σ) - 38.1±11.2, 67 males and 35 females) and 15 healthy age- and gender-matched controls were included in the study. C-reactive protein (CRP, mg/l) and erythrocyte sedimentation rate (ESR, mm/hr) were evaluated as inflammatory markers. Disease activity and functional impairment were moderate to high, mean Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) was 3.07±1.07, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI, mm) - 45.3±18.6, Bath Ankylosing Spondylitis Functional Index (BASFI, mm) - 31.7±22.9.Serum levels of TGF-β1 (pmol/l) and Scl (pmol/l) were measured by ELISA. Spine MRI imagines were assessed for active inflammatory lesions using Berlin method (0-69, n=19). Active and chronic MRI changes in SIJ were scored by Spondyloarthritis Research Consortium of Canada (SPARCC) score (0-72) and Danish scoring method (0-48), respectively (n=67). Spearman correlation coefficient and Student t-test were used for statistical analysis.Results:Mean value of laboratory and MRI parameters were: CRP – 20.9±31.5, ESR – 27.1±22.1, Berlin score was 3.93±3.87, SPARCC – 22.5±11.9, Danish score – 20.5±9.83.Patients with SpA had significantly lower serum levels of biomarkers compared with the healthy controls: 285.3±186.9 vs 443.2±84.3, p=0.0017 - for TGF-β1, and 21.7±13.5 vs 31.2±10.5, p<0.0001 – for Scl.There were significant positive correlations for TGF-β1: strong - with active spine lesions by Berlin method (r=0.810, p<0.01), and weak - with CRP level (r=0.224, p=0.024). There were no correlations with MRI inflammatory changes in SIJ.Scl had weak negative correlation with SPARCC (r=-0.265, p=0.030), but not with Danish or Berlin scores.There were no other correlations, including ASDAS-CRP, BASDAI and BASFI for both TGF- β1 and Scl.Conclusion:Serum TGF- β1 and Scl levels are significantly lower in SpA patients comparing with non-SpA subjects. TGF- β1 positively correlates with disease activity (CRP and active MRI lesions in spine), but has no correlations with SIJ inflammation assessed by MRI. Scl negatively correlates with inflammatory MRI changes in SIJ, but not in the spine.References:[1]Vaez F. Rheum Res. 2017; 2(3): 103-107[2]Perrotta FM. J Immunol Res. 2018. doi: 10.1155/2018/9101964Disclosure of Interests:None declared


Reumatismo ◽  
2017 ◽  
Vol 69 (4) ◽  
pp. 156 ◽  
Author(s):  
R. Talotta ◽  
S. Bongiovanni ◽  
T. Letizia ◽  
F. Rigamonti ◽  
F. Atzeni ◽  
...  

The aim was to evaluate the role of klotho in the pathogenesis of systemic sclerosis (SSc), through the measurement of its serum concentration in SSc patients compared to healthy controls, and to assess the association with cutaneous and visceral involvement. Blood samples obtained from both SSc patients and healthy controls were analysed by an ELISA assay for the detection of human klotho. SSc patients were globally evaluated for disease activity and assessed through the modified Rodnan’s Skin Score, Medsger’s scale, pulmonary function tests, 2D-echocardiography, nailfold capillaroscopy and laboratory tests. Our cohort consisted of 69 SSc patients (61 females, mean age 64.5±12.5 years, median disease duration 9.0 (IQR 8) years) and 77 healthy controls (28 females, mean age 49.7±10.2 years). In the group of SSc patients, 19 (27.5%) suffered from a diffuse form of SSc. All patients were receiving IV prostanoids, and some of them were concomitantly treated with immunosuppressive drugs (prednisone, hydroxychloroquine, mofetil mycophenolate, methotrexate, cyclosporin A and azathioprine). The median serum concentration of klotho was significantly lower in patients compared to controls (0.23 ng/mL vs 0.60 ng/mL; p<0.001). However, Spearman’s test showed no significant association between klotho serum levels and disease activity, concerning either clinical, laboratory or instrumental findings. Our data show a significant deficit of klotho in SSc patients although any significant association was detected between klotho serum concentration and the clinical, laboratory or instrumental features of the disease. However, due to the limits of the study, further investigations are required.


2009 ◽  
Vol 37 (2) ◽  
pp. 257-264 ◽  
Author(s):  
WOON PANG KUAN ◽  
LAI-SHAN TAM ◽  
CHUN-KWOK WONG ◽  
FANNY W.S. KO ◽  
TENA LI ◽  
...  

Objective.To assess whether serum levels of CC and CXC chemokines correlate with disease activity in patients with rheumatoid arthritis (RA), and to determine whether these effects predict clinical response.Methods.Serum levels of the chemokines CC (CCL2, CCL5) and CXC (CXCL8, CXCL9, CXCL10) were quantified at baseline and after 12 weeks of treatment with disease-modifying antirheumatic drugs or biologic agents in 28 patients using flow cytometry. Serum from 40 healthy individuals was collected for comparison at baseline. Response to treatment was classified according to the European League Against Rheumatism (EULAR) response criteria. Remission of disease was defined as a Disease Activity Score < 2.6.Results.The baseline serum concentrations of CC and CXC chemokines were significantly elevated in patients with active RA compared to healthy controls (p < 0.05) except for CCL2. Significant improvement in all disease activity measurements was observed after 12 weeks of treatment. Seventeen (60.7%) patients achieved good to moderate response based on the EULAR response criteria, and 5 (17.9%) patients achieved remission. The improvement in clinical activity in patients with RA was accompanied by a significant reduction in the serum concentration of CXCL9 and CXCL10 (p < 0.001). A significant reduction in the serum level of CXCL10 was also observed in the group that achieved EULAR response. Serum concentration of CCL5 remained significantly elevated in patients with RA (n = 5) who achieved remission compared to the healthy controls (p < 0.05).Conclusion.Serum concentration of CXCL9 and CXCL10 may serve as sensitive biomarkers for disease activity in patients with RA.


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