Ankylosing Spondylitis Disease Activity Research Articles

Comparative study between diffusion weighted imaging and contrast-enhanced MRI in assessment of the activity of ankylosing spondylitis

Objective To compare the value of assessment with DWI and contrast-enhanced MRI (CE-MRI) in activity of sacroiliitis of patients with ankylosing spondylitis(AS). Methods Ninety-six patients conforming to modified New York criteria were prospectively collectedas the AS group, and twenty-one healthy volunteers were enrolled into the control group. According to the Bath AS disease activity index (BASDAI), erythrocyte sedimentation rate and C-reaction protein, AS patients were divided into the active AS group (n=60) and the chronic AS group (n=36). All subjects were performed with conventional MRI, DWI and CE-MRI of bilateral sacroiliac joints. The MRI manifestations were reviewed and the ADC values and signal intensity enhancement rate (ΔSI) were measured.ANOVA was performed for the comparison of ΔSI and ADC values among active AS group, chronic AS group and control group with BASDAI and lab test results as the gold standards. ROC was analyzed with ΔSI and ADC values for activity of AS and paired samples t test was obtained to comparethe areas under the ROC of ΔSI and ADC values. Results Among 96 cases of AS patients, MRI of sacroiliac jointsshowed that 62 cases had subchondral bone edema (57 cases of active group, 5 cases of chronic group), that 11 cases had bone surface erosion(4 cases of active group, 7 cases of chronic group), that 15 cases had bone sclerosis(6 cases of active group, 9 cases of chronic group) and that 58 cases had fat deposition on the sacroiliac joints (27 cases of active group, 31 cases of chronic group). The ΔSI values of the active group, the chronic group and control group were respectively (2.51±1.69) %, (1.19±0.67) % and (0.75±0.21) %, and the ADCvalues were (1.33±0.33) ×10-3, (1.00±0.43) ×10-3 and (0.38±0.13) ×10-3mm2/s. There were significant differences for ΔSI and ADC values among three groups (F=18.375, 16.366. P< 0.01), and statistical significance of ΔSI and ADC values were found between every two groups of three(P< 0.05).The area under the ROC between ΔSI and ADC to determine activity of AS patients were respectively 0.814 and 0.730, which had nostatistical significance(t=1.632, P=0.103). The sensitivity and specificity to determine activity of AS patients by ΔSI=1.44% were 81.67% and 80.00%.The sensitivity and specificity to determine activity of AS patients by ADC=1.15×10-3/mm2 were 76.67% and 71.43%. Conclusion DWI and CE-MRI performed equally in detecting activity of AS patients. Key words: Ankylosing spondylitis; Magnetic resonance imaging; Comparative study

Lifestyle factors may modify the effect of disease activity on radiographic progression in patients with ankylosing spondylitis: a longitudinal analysis

ObjectivesTo investigate the complex relationship between inflammation, mechanical stress and radiographic progression in patients with ankylosing spondylitis (AS), using job type as a proxy for continuous mechanical stress.MethodsPatients from the...

Association of Matrix Metalloproteinases and Their Tissue Inhibitor With Disease Activity and Development in Spondyloarthropathy and Inflammatory Bowel Disease

Objectives: This study aims to investigate whether clinical measures of disease activity and function in ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are associated with matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase -1 (TIMP-1), and if MMPs can be more useful than C-reactive protein and erythrocyte sedimentation rate in predicting disease activity in AS. Patients and methods: MMP-3, MMP-9 and TIMP-1 levels were measured by ELISA in 20 patients with AS, 20 patients with IBD, 20 patients with IBD and AS (35 males, 25 females; mean age 38.1 years; range 19 to 62 years), and 20 healthy volunteers (10 males, 10 females; median age 38.5 years; range 24 to 63 years) as a control group. Bath Ankylosing Spondylitis Disease Activity Index, Truelove-Witts activity criteria for ulcerative colitis, and Crohn's Disease of Activity Index scoring systems were used. Results: Highest MMP-3 level was in IBD group (33.51±59.56 ng/mL, p<0.045). MMP-3 levels were significantly higher in patients with IBD and IBD+AS than in patients with AS (p<0.007 and p<0.035, respectively). Highest MMP-9 levels were in the control group (10.35±2.61 ng/mL, p<0.48). MMP-9 levels were higher in AS group patients than those in IBD and IBD+AS groups, but the difference was not statistically significant (p<0.494 and p<0.260, respectively). Highest TIMP-1 levels were in the IBD group (8.11 ng/mL, p<0.006). TIMP-1 levels of IBD group were significantly higher than both AS and IBD+AS groups (p<0.033 and p<0.008, respectively). A statistically significant correlation was detected between serum MMP-3 levels and disease activity and Bath Ankylosing Spondylitis Disease Activity Index score in patients with AS (r=0.841, p<0.05). Conclusion: We concluded that serum MMP-3 levels may be a better biomarker than C-reactive protein and erythrocyte sedimentation rate in showing disease activity in AS.

Association of β-defensin gene copy number variations with ankylosing spondylitis in Chinese population: A case–control study

Objectives. To explore the association of β-defensin gene copy number variations (CNVs) with ankylosing spondylitis (AS).Methods. In this study, 405 unrelated Chinese Han patients with AS and 401 unrelated healthy controls were enrolled. The copy numbers of DEFB4 gene (2 fragments) were measured by AccuCopy™ methods. The association of DEFB4 gene CNVs with AS susceptibility was analyzed by chi-square and logistic regression models. Besides, P values, odds ratio, and 95% confidence intervals (CIs) were used to estimate the effects of risk.Results. The range of DEFB4_1 CN was 0–7 and the range of DEFB4_2 CN was 1–8 both in patients and controls. P values of χ2 trend test for the association of DEFB4_1 and DEFB4_2 with AS were 0.607 and 0.005, respectively. The results of DEFB4_2, compared with the individual having median 3 copies, those carrying ≤ 2-copies [OR = 0.68, 95%CI: (0.46, 0.99), P = 0.049; adjusted OR = 0.69, 95%CI(0.47, 1.03), P = 0.067.]; and those carrying ≥ 4-copies [OR = 0.62, 95%CI: (0.45, 0.86), P = 0.004; adjusted OR = 0.64, 95%CI: (0.46, 0.88), P = 0.006], were significantly associated with decreasing risk of AS. Univariate analysis showed that both DEFB4_1 and DEFB4_2 were associated with Bath AS Disease Activity Index or BASDAI. After adjusted by age, sex, and disease duration, the results changed little, which demonstrated that high copies may be linked with decrease in the risk of disease severity [OR = 0.71, 95%CI: (0.56, 0.90), P = 0.005; OR = 0.75, 95%CI: (0.60, 0.94), P = 0.013, respectively].Conclusions. The CNs of DEFB4 gene may be associated with AS and involved in disease progression.

Sexual dysfunctions and lower urinary tract symptoms in ankylosing spondylitis

To determine sexual dysfunctions and urinary symptoms in male ankylosing spondylitis (AS) patients and their association with various disease and patient factors. In this prospective case control study conducted at a tertiary care teaching institution, 100 males with AS were compared to 100 controls using International Index of Erectile Function-15 (IIEF), International Prostate Symptom Score (IPSS), Hospital Anxiety and Depression Scale (HADS) and a global question for overall relationship with their partners. Bath AS Functional Index (BASFI), visual analogue scale pain scores, patient global assessment scale and Bath AS Disease Activity Index were also assessed in the AS group. Chi-square test, unpaired t-test and univariate and multivariate binary logistic regression analyses were used to analyze the data. Anxiety, depression, erectile dysfunction (ED), orgasmic dysfunction, intercourse dissatisfaction, overall sexual dissatisfaction, altered overall relationship with partner and lower urinary tract symptoms (LUTS) were significantly (P < 0.05) higher in the AS group as compared to controls. Sexual desire, severe LUTS and bothersome LUTS (quality of life score > 2) were not different (P = 0.76, 0.82 and 0.30 respectively) between the two groups. ED was associated with anxiety, depression, longer disease duration, higher BASFI and higher age in AS patients (P = 0.02, 0.001, 0.02, 0.003 and 0.001 respectively). AS is associated with higher incidence of sexual dysfunction in male patients. ED is associated with anxiety, depression, longer duration of disease, higher BASFI score and higher age in AS patients.

Ankylosing Spondylitis patients with Type D personality have worse clinical status

Objectives. Type D personality was identified as an important factor that can explain the differences in clinical outcomes in various diseases. The aim of this study is to clarify the relationships between Type D personality and clinical status of patients with Ankylosing Spondylitis (AS).Methods. The scores of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), the Bath Ankylosing Spondylitis Functional Index (BASFI), the 36-Item Short-Form Health Survey (SF-36), and 14-item Type D Scale (DS-14) were noted.Results. We found significantly higher levels of the BASDAI, the BASFI, and the SF-36 mental subscale scores in patients with Type D personalities compared to those who were Non-Type D (p < 0.05). The total DS-14 scores were found to be correlated with the scores of physical and mental subscales of SF-36, the BASDAI, the BASFI, ASDAS-CRP, and ESR (p < 0.05). In logistic regression analysis, the occurrence of Type D personality was found to be an independent predictor for disease activity of AS due to BASDAI and ASDAS-ESR (p = 0.016, OR, 95% CI = 2.98,1.23–7.22; p = 0.022, OR, 95% CI = 2.78,1.16–6.63 respectively).Conclusions. Patients may over-rate self-reported measurements such as the BASDAI, BASFI, and SF-36 related to their interpersonal characteristics. Therefore, including the Type D personality, which is a stable construct in evaluating AS patients with brief and valid DS-14, may be noteworthy.

Relationship between physical function, disease activity, spinal mobility and bone parameters (trabecular bone score and bone mineral density) in ankylosing spondylitis patients

This study aimed to evaluate the relationship between physical function, disease activity, spinal mobility and bone parameters in ankylosing spondylitis (AS) patients. Fifty patients (27 men and 23 women) were examined. The clinical assessment included Bath AS Disease Activity Index, AS Disease Activity Score, Bath AS Functional Index, Bath AS Metrology Index (BASMI). Lumbar spine and femoral neck bone mineral density (BMD), spinal trabecular bone score (TBS) and the TBS T-score were calculated by dual-energy X-ray absorptiometry. Prevalence rates for osteoporosis and osteopaenia were 14% and 36%, respectively and for partially and fully degraded microarchitecture – 34% and 16%, respectively. A similar inverse correlation was observed between BASMI and TBS, TBS T-score and femoral BMD bone parameters, which were significantly lower in patients ≥45 years of age. No significant correlations were detected between any bone parameter and indicators of disease activity and physical function. Patients with a disease duration of ≥10 years tended to exhibit either normal or elevated spine BMD. Femoral BMD was lower in men. The higher BASMI was associated with an increased likelihood of TBS < 1.350 (odds ratio (OR) = 1.44, 1.05–1.97, p = 0.024) and TBS T-score < –1.00 (OR = 1.55, 1.11–2.16, p = 0.01). In summary, lumbar spine BMD can be erroneously influenced by osteoproliferation, unlike the TBS and TBS T-score. The limitations in spinal mobility predicted abnormal results for these two TBS parameters. TBS may be a better indicator of bone health than BMD in AS.

CRP and ASDAS are associated with future elevated arterial stiffness, a risk marker of cardiovascular disease, in patients with ankylosing spondylitis: results after 5-year follow-up

ObjectiveTo identify factors associated with elevated arterial stiffness in a 5-year follow-up of patients with ankylosing spondylitis (AS).MethodsC-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath AS disease activity index (BASDAI)...

Rosuvastatin improves endothelial dysfunction in ankylosing spondylitis.

Enhanced cardiovascular risk in ankylosing spondylitis (AS) provides a strong rationale for early therapeutical intervention. In view of the proven benefit of statins in atherosclerotic vascular disease, we aimed to investigate the effect of rosuvastatin on endothelial dysfunction (ED) and inflammatory disease activity in AS. In a single-blind, placebo-controlled, parallel study, 32 AS patients were randomized to receive 24weeks of treatment with rosuvastatin (10mg/day, n = 17) and placebo (n = 15) as an adjunct to existing stable antirheumatic drugs. Flow-mediated dilatation (FMD) was assessed by AngioDefender™ (Everest Genomic Ann Arbor, USA). Inflammatory measures (BASDAI, BASFI, CRP and ESR) and pro-inflammatory cytokines (tumour necrosis factor-alpha [TNF-α], interleukin-6 [IL-6] and interleukin-1 [IL-1]) were measured at baseline and after treatment. Lipids and adhesion molecules (intracellular adhesion molecule [ICAM-1] and vascular cell adhesion molecule [VCAM-1]) were estimated at baseline and after treatment. At baseline, inflammatory measures, pro inflammatory cytokines and adhesion molecules were elevated among both groups. After treatment with rosuvastatin, FMD improved significantly (p < 0.01). Levels of inflammatory measures, TNF-α, IL-6 and ICAM-1 decreased significantly (p < 0.01) after treatment with rosuvastatin. Rosuvastatin exerted positive effect on lipid spectrum. No significant change in the placebo group. Significant negative correlation was observed between FMD and IL-6, ICAM-1, CRP after treatment with rosuvastatin. First study to show that rosuvastatin improves inflammatory disease activity and ED in AS. Rosuvastatin lowers the proinflammatory cytokines, especially IL-6 and TNF-α, which downregulates adhesion molecules and CRP production which in turns improves ED. Improvement in ED in AS occurs through both cholesterol-independent and cholesterol-dependent pathways. Rosuvastatin can mediate modest but clinically apparent anti-inflammatory effects with modification of vascular risk factors in the context of high-grade autoimmune inflammation of AS.

Circulating levels of inflammatory cytokines and cytokine receptors in patients with ankylosing spondylitis: a cross-sectional comparative study

Objectives: Insight into the most important inflammatory pathways in ankylosing spondylitis (AS) could be of importance in risk stratification and the development of treatment strategies. Therefore, we aimed to compare circulating levels of inflammatory biomarkers between AS patients and controls, and explore associations between these biomarkers and clinical measures of disease activity.Method: In a cross-sectional study, 143 AS patients were compared with 124 population controls. Blood samples were analysed by immunoassays for interleukin (IL)-6, IL-17a, IL-23, soluble tumour necrosis factor receptor 1 (sTNF-R1) and 2 (sTNF-R2), and osteoprotegerin (OPG). Disease activity was measured by the AS Disease Activity Score (ASDAS) and the Bath AS Disease Activity Index (BASDAI).Results: Analysis of covariance (ANCOVA) demonstrated elevated plasma levels of sTNF-R1 [geometrical mean 0.94 (95% CI 0.88–1.00) vs. 0.83 (95% CI 0.78–0.89) ng/mL, p < 0.01] and OPG (2.3, 95% CI 2.1–2.4 vs. 2.0, 95% CI 1.9–2.2 ng/mL, p = 0.02) and, although not significant, of IL-23 (122, 95% CI 108–139 vs. 106, 95% CI 93–120 pg/mL, p = 0.07) in AS patients vs. controls. More AS patients had a high level of sTNF-R2 than controls (22 vs. 1, p < 0.01). No differences between the groups were seen for IL-6 and IL-17a. In patients, no significant associations were seen between inflammatory markers and disease activity measures after adjusting for personal characteristics.Conclusion: Significantly higher plasma levels of sTNF-R1, sTNF-R2, and OPG and numerically but non-significantly higher levels of IL-23 were found in AS patients compared to controls, indicating that these cytokines and cytokine receptors are important inflammatory pathways. Clinical measures of disease activity were not significantly correlated with circulating inflammatory markers.

Risk of falls in patients with ankylosing spondylitis.

Risk of vertebral fractures is increased in patients with ankylosing spondylitis (AS). The underlying mechanisms for the elevated fracture risk might be associated with bone and fall-related risks. The aims of this study were to evaluate the risk of falls and to determine the factors that increase the risk of falls in AS patients. Eighty-nine women, 217 men, a total of 306 AS patients with a mean age of 40.1 ± 11.5 years from 9 different centers in Turkey were included in the study. Patients were questioned regarding history of falls within the last 1 year. Their demographics, disease characteristics including Bath AS Disease Activity Index, Bath AS Metrology Index (BASMI), Bath AS Functional Index (BASFI), and risk factors for falls were recorded. The Short Physical Performance Battery (SPPB) test was used for evaluation of static and dynamic balance. Erythrocyte sedimentation rate, C-reactive protein, and 25-hydroxyvitamin D levels were measured. Forty of 306 patients reported at least 1 fall in the recent 1 year. The patients with history of falls had higher mean age and longer disease duration than did nonfallers (P = 0.001). In addition, these patients' BASMI and BASFI values were higher than those of nonfallers (P = 0.002; P = 0.000, respectively). We found that the patients with history of falls had lower SPPB scores (P = 0.000). We also found that the number of falls increased with longer disease duration and older age (R = 0.117 [P = 0.041] and R = 0.160 [P = 0.005]). Our results show that decreased SPPB scores were associated with increased number of falls (R = 0.183, P = 0.006). Statistically significant correlations were found between number of falls and AS-related lost job (R = 0.140, P = 0.014), fear of falling (R = 0.316, P = 0.000), hip involvement (R = 0.112, P = 0.05), BASMI (R =0.234, P = 0.000), and BASFI (R = 0.244, P = 0.000). Assessment of pain, stiffness, fatigue, and lower-extremity involvement as well as asking for a history of falls will highlight those at high risk for further falls. In addition to the general exercise program adopted for all patients, we suggest that a balance rehabilitation program should be valuable for the patients with risk factors for fall. Exercise may improve fear of falling and BASFI and BASMI scores. However, further study is needed to investigate these hypotheses. We believe that clinicians should train and support the patients via reducing fear of falls and maintaining good posture and functional capacity.

Interleukin-37 is increased in ankylosing spondylitis patients and associated with disease activity.

BackgroundInterleukin-37 (IL-37) has been known to play an immunosuppressive role in various inflammatory disorders, but whether it participates in the regulation of pathogenesis of ankylosing spondylitis (AS) has not been investigated. Here, we examined the serum levels of IL-37 and its clinical association in AS, and explored the anti-inflammatory effects of IL-37 on peripheral blood mononuclear cells (PBMCs) from AS patients.MethodsThe mRNA levels of IL-37, TNF-α, IL-6, IL-17, and IL-23 in PBMCs and their serum concentrations from 46 AS patients were examined by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunoassay (ELISA), respectively. The correlations between serum IL-37 levels with disease activity, laboratory values and pro-inflammatory cytokines in AS were analyzed by Spearman correlation test. PBMCs from 46 AS patients were stimulated with recombinant IL-37 protein, expressions of TNF-α, IL-6, IL-17 and IL-23 were determined by RT-PCR and ELISA.ResultsCompared to healthy controls (HC), AS patients and active AS patients showed higher levels of IL-37 in PBMCs and serum respectively. Strikingly, serum IL-37 levels were higher in AS patients with osteoporosis than those without. Serum levels of IL-37 were correlated with laboratory values as well as TNF-α, IL-6 and IL-17, but not IL-23 in patients with AS. The productions of pro-inflammatory cytokines such as TNF-α, IL-6, IL-17, IL-23 in PBMCs from AS patients were obviously attenuated after recombinant IL-37 stimulation, but not in the HC.ConclusionThe higher levels of IL-37 were found in AS patients, which were correlated with disease activity and AS related pro-inflammatory cytokines. More importantly, IL-37 inhibits the expressions of the pro-inflammatory cytokines from PBMCs in AS patients, indicating the potential anti-inflammatory role of IL-37 in AS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0394-3) contains supplementary material, which is available to authorized users.

Reduced serum B7-H3 levels in patients with ankylosing spondylitis.

This study aimed to investigate molecule B7-H3 expression profiles of patients with ankylosing spondylitis (AS) and the clinical significance of B7-H3 in the pathogenesis of AS. Serum B7-H3 levels were measured by ELISA in patients with AS and healthy controls. The expression of B7-H3 protein and mRNA on CD14+ monocytes of peripheral blood mononuclear cells (PBMCs) and serum levels of T cell-associated cytokines were also analyzed. The serum B7-H3 levels in AS patients were significantly lower than in healthy controls. The expression of B7-H3 protein and mRNA on CD14+ monocytes of PBMCs and serum levels of TNF-α, IL-6, and IL-17A in AS patients were significantly higher than in controls. The reduced serum B7-H3 level was highly negatively correlated with AS Disease Activity Score (ASDAS), TNF-α, and IL-17A. Upregulated B7-H3 protein may play a role in the pathogenesis of AS by binding its receptor on T cells.

Neutrophil-to-lymphocyte ratio is involved in the severity of ankylosing spondylitis.

Ankylosing spondylitis (AS) is a progressive chronic inflammatory disease mainly characterized by axial skeleton and sacroiliac joint involvement. We aimed to investigate the relation between neutrophil-to-lymphocyte ratio (NLR) and disease severity of AS and to explore its availability in clinical practice. A total of 102 AS patients and 60 individuals who were age- and gender-compatible with the control group were included into the study. Patients were divided into 2 groups according to Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores. Patients with BASDAI scores < 4 were considered to be having mild disease activity, whereas those with scores ≥ 4 were considered to be displaying severe disease activity. Hemogram test during the diagnosis, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and other laboratory values of the control group were recorded. NLR was observed to be higher in AS patients compared to the controls (2.47 ± 1.33 and 1.72 ± 0.47; respectively; p<0.0001). NLR was observed to be significantly higher in severe AS disease activity compared to the mild AS disease activity (2.72 ± 1.41, 2.20 ± 1.19; respectively; p = 0.001). NLR had statistical significant differences between mild disease activity compared to the controls (2.20 ± 1.19 and 1.72 ± 0.47, respectively; p = 0.263). There was a positive correlation between NLR and BASDAI (r = 0.193, p = 0.041). The performance of NLR evaluating the disease severity by Roc analysis had sensitivity of 69%, specificity of 54% (cut-off value 1.91), and AUC of 0.652 (95% Cl, 0.549-0.755) (p = 0.006). NLR may be a simple and inexpensive marker to indicate disease activity in patients with AS in daily clinical practice (Tab. 3, Fig. 3, Ref. 25).

Expression of TNF-α, VEGF, and MMP-3 mRNAs in synovial tissues and their roles in fibroblast-mediated osteogenesis in ankylosing spondylitis

The aim of this study was to explore the mRNA levels of tumor necrosis factor-α (TNF-α), vessel endothelial growth factor (VEGF), and matrix metalloproteinase-3 (MMP-3) in synovial tissues in ankylosing spondylitis (AS), and to analyze the functions of these proteins in the differentiation of AS synovial tissue fibroblasts into osteoblasts (OB) and osteoclasts. Synovial tissue samples from 22 AS patients and 22 normal individuals were collected. In situ hybridization was utilized to detect TNF-α, VEGF, and MMP-3 transcripts. After counting numbers of positive cells, Spearman analysis was used to determine the correlation between transcriptional levels of the three mRNAs and the AS disease activity index (BASDAI) and the C-response protein (CRP) levels. With the addition of TNF-α, VEGF, or both factors into cultured normal synovial fibroblasts, osteocalcin (bone gla protein, BGP) secretion levels were compared. We found that expression of TNF-α, VEGF, and MMP-3 was identified exclusively in the disease group. mRNA levels were significantly positively correlated with BASDAI (r = 0.42, 0.38, and 0.47, respectively; P < 0.05) and CRP (r = 0.44, 0.34, and 0.47 respectively; P < 0.05) scores. The secretion level of BGP in normal synovial fibroblasts increased progressively with increasing concentrations of VEGF or TNF-α (P < 0.01 compared to levels before treatment). Furthermore, co-incubation using both VEGF and TNF-α significantly elevated BGP levels compared to the single addition of VEGF or TNF-α (P < 0.01). These results suggest TNF-α, VEGF, and MMP-3 might directly participate in the differentiation of fibroblasts into OBs.

Serum Vitamin D and Pyridinoline Cross-Linked Carboxyterminal Telopeptide of Type I Collagen in Patients with Ankylosing Spondylitis.

Objective. To assess the serum vitamin D and ICTP levels in patients with ankylosing spondylitis (AS) and investigate their relationship with disease activity and bone mineral density (BMD). Method. 150 patients and 168 controls were included. Serum 25(OH)D, ICTP, C-reaction protein (CRP), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), and Hip BMD were assessed in patients. 25(OH)D and ICTP were detected in controls. Results. The serum 25(OH)D in AS was 57.92 ± 24.42 nmol/L, significantly lower than controls (91.24 ± 42.02 nmol/L). Serum ICTP in AS was 5.72 ± 3.88 ug/L, significantly higher than controls (3.69 ± 1.26 ug/L). ICTP level was higher in men than in women patients (6.07 ± 4.05 versus 3.84 ± 1.96 ug/L, P ≤ 0.01); it was also higher in JAS than in AAS (9.52 ± 3.79 versus 5.27 ± 3.65 ug/L, P ≤ 0.01). Furthermore, 25(OH)D was negatively correlated with ICTP. Low 25(OH)D and high ICTP were one of the reasons of AS patients' low hip BMD. Besides, a significant relationship was found between serum ICTP and CRP. Conclusion. There was a high incidence of vitamin D inadequacy in AS. Serum ICTP level was elevated in AS, especially in JAS and male patients. 25(OH)D and ICTP seem to be valuable markers to detect bone loss in AS.

Efficacy of high intensity exercise on disease activity and cardiovascular risk in active axial spondyloarthritis: a randomized controlled pilot study.

BackgroundPhysical therapy is recommended for the management of axial spondyloarthritis (axSpA) and flexibility exercises have traditionally been the main focus. Cardiovascular (CV) diseases are considered as a major health concern in axSpA and there is strong evidence that endurance and strength exercise protects against CV diseases. Therefore, the aim of this study was to investigate the efficacy of high intensity endurance and strength exercise on disease activity and CV health in patients with active axSpA.MethodsIn a single blinded randomized controlled pilot study the exercise group (EG) performed 12 weeks of endurance and strength exercise while the control group (CG) received treatment as usual. The primary outcome was the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS). Secondary outcomes included patient reported disease activity (Bath AS Disease Activity Index [BASDAI]), physical function (Bath AS Functional Index [BASFI]), and CV risk factors measured by arterial stiffness (Augmentation Index [Alx]) and Pulse Wave Velocity [PWV]), cardiorespiratory fitness (VO2 peak) and body composition. ANCOVA on the post intervention values with baseline values as covariates was used to assess group differences, and Mann Whitney U-test was used for outcomes with skewed residuals.ResultsTwenty-eight patients were included and 24 (EG, n = 10, CG, n = 14) completed the study. A mean treatment effect of −0.7 (95%CI: −1.4, 0.1) was seen in ASDAS score. Treatment effects were also observed in secondary outcomes (mean group difference [95%CI]): BASDAI: −2.0 (−3.6, −0.4), BASFI: −1.4 (−2.6, −0.3), arterial stiffness (estimated median group differences [95% CI]): AIx (%): −5.3 (−11.0, −0.5), and for PVW (m/s): −0.3 (−0.7, 0.0), VO2 peak (ml/kg/min) (mean group difference [95%CI]: 3.7 (2.1, 5.2) and trunk fat (%): −1.8 (−3.0, −0.6). No adverse events occurred.ConclusionHigh intensity exercise improved disease activity and reduced CV risk factors in patients with active axSpA. These effects will be further explored in a larger trial.Trial RegistrationClinicalTrials.gov NCT01436942

Role of Protein Phosphatase Magnesium‐Dependent 1A and Anti–Protein Phosphatase Magnesium‐Dependent 1A Autoantibodies in Ankylosing Spondylitis

ObjectiveAlthough ankylosing spondylitis (AS) is driven by immune‐mediated processes, little is known about the presence and role of autoantibodies in this disease. This study was undertaken to investigate whether autoantibodies occur in and are involved in AS.MethodsWe performed human protein microarray analysis of sera derived from patients with AS or other autoimmune disorders to identify autoantibodies associated specifically with AS, and identified autoantibody targeting of protein phosphatase magnesium‐dependent 1A (PPM1A) in AS. We performed enzyme‐linked immunosorbent assay (ELISA) analysis of sera from 2 independent AS cohorts to confirm autoantibody targeting of PPM1A, and to assess associations between levels of anti‐PPM1A antibodies and AS disease severity or response to anti–tumor necrosis factor (anti‐TNF) therapy (as measured by Bath AS Disease Activity Index [BASDAI] score). Levels of anti‐PPM1A antibodies were also evaluated in sera from rats transgenic for HLA–B27 and human β2‐microglobulin. The expression of PPM1A was assessed by immunohistochemistry in synovial tissue samples from patients with AS, rheumatoid arthritis, or osteoarthritis. The role of PPM1A in osteoblast differentiation was investigated by gene knockdown and overexpression.ResultsAS was associated with autoantibody targeting of PPM1A, and levels of anti‐PPM1A autoantibodies were significantly higher in patients with more advanced sacroiliitis and correlated positively with BASDAI score after treatment with anti‐TNF agents. The levels of anti‐PPM1A autoantibodies were also higher in the sera of transgenic rats that are prone to develop spondyloarthritis than in those that are not. PPM1A was expressed in AS synovial tissue, and PPM1A overexpression promoted osteoblast differentiation, whereas PPM1A knockdown suppressed it.ConclusionAnti‐PPM1A autoantibodies are present in AS, and our findings suggest that PPM1A may contribute to the pathogenic bone ankylosis characteristic of AS.

Etanercept in the treatment of ankylosing spondylitis: A systematic review and meta-analysis.

Etanercept (ETN) has been widely applied in the treatment of ankylosing spondylitis (AS). As the use of ETN has increased, associated adverse effects have been reported frequently. Previous meta-analyses have focused on comparing the differences in clinical outcomes between ETN and placebo (PBO). The present meta-analysis evaluated randomised controlled trials (RCTs) to compare the effects of ETN and a PBO or sulfasalazine (SSZ) in patients with AS. The study population characteristics and the main results, including the Assessment in AS 20% response (ASAS 20), the Bath AS Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI), were extracted. The pooled odds ratios (ORs) or weighted mean differences (MDs) were calculated using a fixed or random effects model. Fifteen randomised controlled trials (RCTs) involving 2,194 subjects were included. Compared with a PBO, ETN significantly improved the ASAS 20 [P<0.00001; OR, 8.25; 95% confidence interval (CI), 5.92–11.50], BASDAI (P<0.00001; MD, −18.81; 95% CI, −24.47 to −13.15) and BASFI (P<0.00001; standard MD, −0.68; 95% CI, −0.85 to −0.50). In comparison with SSZ, ETN significantly decreased the BASDAI (P<0.00001; MD, −2.40; 95% CI, −2.89 to −1.90) and C-reactive protein (CRP) levels (P<0.0001; MD, −8.01; 95% CI, −11.73 to −4.29). The most common adverse effect of ETN was an injection site reaction. This meta-analysis shows that ETN monotherapy is effective in improving physical function and reducing disease activity in patients with AS. Compared with SSZ, ETN markedly decreased the BASDAI and CRP levels. However, the efficacy of ETN in treating AS requires further evaluation by more RCTs in a larger population of patients prior to recommending ETN as a substitute for synthetic disease-modifying antirheumatic drug (DMARD) monotherapy, or combinations of synthetic DMARDs.

Positive and negative affective states and disease activity in ankylosing spondylitis.

The aim of the study was to explore the influence of psychological affective states such as cheerfulness and bad mood on self-reported disease activity in patients with ankylosing spondylitis (AS) while controlling for demographic and clinical variables. Patients attending a biological therapy unit were selected for a cross-sectional study if they met the criteria for AS and were already receiving treatment. Their psychological affective state was assessed with the state version of the State-Trait Cheerfulness Inventory. Clinical variables included were patient-reported disease activity using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and acute-phase reactants. We performed univariate and multivariate analyses to verify the robustness of the relationship between psychological affective states and disease activity. We also explored whether disease activity, measured either by self-report or by acute-phase reactants, was influenced by patient's overall affective state. In the recruited 31 patients with AS, overall affective state contributed significantly to the variance in BASDAI scores, adding 21.8% to the overall R-square of the predictive power of clinical and demographic variables (combined R-square = 17%). A higher positive affective state was associated with lower values of C-reactive protein (p < 0.05). Results of a bootstrapping procedure showed that the relationship between C-reactive protein levels and BASDAI scores was mediated by overall affective state. In patients with AS, affective state can induce variability in self-reported disease activity. Patients' overall affective state can explain the relationship between acute-phase reactants and self-reported scores. These findings suggest interesting possibilities for the monitoring of disease activity in AS.