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Ankylosing spondylitis is a complicated consequence of genetic predisposition and environmental factors. Enthesitis is believed to be the hallmark of ankylosing spondylitis, and the chronic inflammatory state of this disease is perpetuated by the disturbances of both the innate immune system and the acquired immune system. To clarify the alteration of immune system in patients with AS, we conducted a meta-analysis concerning the proportions of major lymphocyte subsets in the peripheral blood of AS patients. We systematically searched PubMed and China National Knowledge Infrastructure (CNKI) for articles related to this subject. A total of 95 articles involving 4,020 AS patients and 3,065 healthy controls were included in the analysis. This meta-analysis is performed on R platform using R package “meta”, and Egger’s tests were used to determine the presence of publication bias. Results showed that the percentages of T cells, NK cells and NKT cells were not significantly different between AS patients and healthy controls, but B cells were significantly increased. Among the subsets of T cells, the proportions of CD4+ T cells, Th17 cells, Tfh cells as well as Th1/Th2 ratio were significantly increased, while Tregs were significantly decreased. Subgroup analysis showed that the proportions of Th17 among both PBMCs, T cells and CD4+ T cells were significantly elevated, while Tregs were only significantly lower in PBMCs. Subgroup analysis also demonstrated that Tregs defined by “CD4+CD25+FoxP3+”, “CD4+CD25+CD127low”or “CD4+CD25+CD127-”were significantly downregulated, indicating that the selection of markers could be critical. Further study is warranted in order to elucidate the complicated interactions between different lymphocyte subsets in AS patients. This study implied that the disequilibrium between Th17 and Tregs, as well as between Th1 and Th2 could contribute to the pathogenesis of ankylosing spondylitis, further cementing the understanding that ankylosing spondylitis is a consequence of disrupted balance of innate immune system and acquired immune system.

Fibromyalgia (FM) and ankylosing spondylitis (AS) are both rheumatic diseases characterized by significant musculoskeletal pain. In this study, we investigated the differences of the resting-state network (RSN) connectivity and gray matter volume (GMV) between FM, AS and healthy controls (HCs). We recruited 38 FM patients, 82 AS patients and 61 HCs in this study. All the participants underwent resting-state functional MRI (rs-fMRI) scans in a GE 3.0T MR system. Independent component analysis (ICA) was conducted on the rs-fMRI data, and group differences of the rsFC between different resting-state networks were calculated using dual regression. We also conducted voxel-based morphometry (VBM) analysis to investigate the differences of the GMV in FM, AS and HCs. The rsFC between the dorsal default mode network (DDMN) and the body of left caudate nucleus was significantly decreased in FM patients in comparison to AS patients (87 voxels, p = 0.025). VBM analysis showed that the GMV of the left posterior lobe of cerebellum was significantly increased in FM patients compared with AS patients (88 voxels, p = 0.036). Neither ICA nor VBM analysis revealed significant differences of RSN connectivity or GMV between FM patients and HCs. The altered rsFC between DMN and the caudate nucleus suggested an aberrant cortico-striato-thalamo-cortical circuit in FM patients, indicating aberrant reward processing, with potential association with mood, motivation and cognitive functions. The increased GMV in the left posterior lobe of cerebellum indicated the participation of cerebellum in the abnormal pain processing in FM patients.

Lower back pain comprises the majority of the disease burden of patients with ankylosing spondylitis (AS), while the alterations of the large-scale brain networks could be implicated in the neuropathophysiology of pain. The frontoparietal network (FPN) is known as a pain modulation hub, with key nodes dorsolateral prefrontal cortex (dlPFC) and ventrolateral prefrontal cortex (vlPFC) participating in the pain modulation and reappraisal process. In this study, we adopted the analytical approaches of independent component analysis (ICA) and seed-based correlation analysis (SCA) to examine the resting-state functional connectivity (rsFC) of the large-scale brain networks, notably FPN, between 82 AS patients and 61 healthy controls (HCs). We also investigated the correlation between the rsFC and the clinical measures of AS patients. Both ICA and SCA consistently showed that the rsFC between FPN and mPFC, a key node of the default mode network (DMN), was significantly increased in AS. In addition, SCA also identified a cluster at the right posterior lobe of cerebellum which exhibited increased rsFC with the posterior cingulate cortex, and the right lateral prefrontal cortex also showed increased rsFC with the right dlPFC. Correlation analysis showed that the rsFC between mPFC and the left anterior prefrontal cortex was significantly correlated with C-reactive protein in AS. The increased FPN-DMN connectivity could contribute to the neuropathophysiology of lower back pain in AS, with potential association with faulty pain modulation and reappraisal mechanisms facilitated by the FPN.

Evaluate the MRI evidence of active inflammatory and chronic structural damages in radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axial spondyloarthritis (nr-axSpA). A retrospective review of 253 patients who underwent sacroiliac joint (SIJ) MRI between June 2014 and December 2019 was performed. MRI images including short tau inversion recovery scan and T1-weighted spin echo scans were assessed using the Spondyloarthritis Research Consortium of Canada (SPARCC) score and SPARCC MRI SIJ structural score by two independent readers. Higher mean score of inflammatory (SPARCC) was seen in r-axSpA patients when compared with nr-axSpA patients (8.08 4.37, <0.05). Frequencies of MRI structural lesions in r-axSpA patients and nr-axSpA patients were as follows: erosion (65.84 88.23%, =0.002), backfill (33.17 13.73%, <0.001), fat metaplasia (79.21 60.78%, =0.01), and ankylosis (37.13 1.96%, <0.001). Patients with r-axSpA had a higher mean score for fat metaplasia (8.93 4.06, =0.0003) and ankylosis (4.49 0.04, <0.001). More active inflammatory and chronic structural damages except for erosion were seen in r-axSpA patients than nr-axSpA patients, while higher percentage of nr-axSpA patients presented with erosion in MRI.

To study the diagnostic performance of chemical shift-encoded MRI (CSE-MRI) in the diagnosis of axial spondyloarthritis (axSpA). CSE-MRI images were acquired for consecutive patients complaining of back pain as well as healthy volunteers. Proton density fat fraction (PDFF) values were measured independently by two readers. Diagnostic performance of CSE-MRI was analyzed by sensitivity analysis and ROC curve analysis. Logistic regression analysis was employed to investigate the risk factors of extensive fat deposition in the SIJs. A total of 52 r-axSpA patients, 37 nr-axSpA patients, 24 non-SpA patients and 34 healthy volunteers were included. Mean PDFF values in the SIJs of patients with r-axSpA and nr-axSpA (72.7% and 64.5%) were significantly higher than non-SpA patients and healthy volunteers (56.0% and 57.6%) (p<0.001). By defining extensive fat deposition in the SIJs as ≥8 ROIs with PDFF values over 70%, its sensitivity and specificity in diagnosing axSpA reached 72.47% and 86.21%%. By joining bone marrow edema (BME) with ≥8 ROIs (PDFF>70%), 22 (24.71%) and 23 (25.84%) more axSpA patients were classified as SIJ MRI (+) by reader 1 and 2, but specificities decreased by 15.52% and 10.34%. Multivariate logistic regression analysis confirmed longer disease duration as the independent risk factor of extensive fat deposition in SIJs (OR=1.15, 95%CI[1.03, 1.32]), while bDMARDs medication was a protective factor (OR=0.15, 95%CI[0.04, 0.51]). CSE-MRI is a reliable tool to quantitively assess the fat metaplasia in the SIJs of axSpA patients. Extensive fat deposition in the SIJs could add incremental diagnostic value to BME, but at the cost of decreased specificities.

Previous studies have revealed alterations of the functional connectivity of the brain networks in ankylosing spondylitis (AS). Fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) are both voxel-based functional metrics capable of estimating local spontaneous neural activities. This study aimed to investigate the local spontaneous neural activities in AS patients by utilizing the analytical approaches of fALFF and ReHo. A total of 78 AS patients and 59 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. fALFF and ReHo maps were generated to identify brain regions with aberrations of spontaneous neural activities in AS patients. Different frequency bands, including the standard frequency band (0.01-0.1 Hz), slow-5 (0.01-0.027 Hz), and slow-4 (0.027-0.073 Hz), were adopted in the fALFF analysis. Compared with HCs, AS patients exhibited extensive alterations of fALFF and ReHo values in brain regions belonging to the default mode network (DMN), salience network (SN), frontoparietal network (FPN), sensorimotor network, visual network and the cerebellum. Clusters found in the slow-5 band only showed significantly decreased fALFF values, whereas the slow-4 was the major contributor to the elevated fALFF values in the standard band. The fALFF and ReHo analyses consistently revealed significantly altered local spontaneous neural activities in AS patients, especially in the DMN, SN and FPN, comprising the triple network model. The slow-4 band might be more sensitive to the elevated fALFF values in AS patients than the slow-5 band. Our findings provide further evidence that the aberrations of the triple network model serve as an important feature of AS from the perspective of local neural activities.

In this study, we aimed to use a two sample Mendelian randomization (MR) method to identify a potentially causality between waist circumference and the risk of deep vein thrombosis (DVT). With a two-sample MR approach, we analyzed the summary data. The main analysis was performed by using the summary genetic data from two large consortium cohorts. Three MR approaches were used to explore MR estimates of waist circumference for DVT (inverse-variance weighted [IVW] approach, weighted median method and MR-Egger method). A total of 224 single nucleotide polymorphisms (SNPs) were identified associated with the level of waist circumference at statistical significance (P < 5*10 ; linkage disequilibrium r < 0.1). The result of IVW indicated the positive association between waist circumference and the risk of DVT (OR 1.012, 95% CI 1.009-1.014, P 7.627E-17). The other two methods were observed with consistent result. MR-Egger regression analysis indicated that no evidence for the presence of directional horizontal pleiotropy. Additionally, DVT was not a causal factor for waist circumference. In summary, we used the GWAS genetic data from two large consortium cohorts and indicated the positive association between waist circumference and DVT. Further researches are needed to investigate potential mechanism and clarify the role of waist circumference on DVT.

In this study, we aimed to investigate whether there was a pattern of distribution of acute and chronic lesions in the sacroiliac joints (SIJ) of patients with axial spondyloarthritis (axSpA). A total of 96 patients diagnosed as axSpA were retrospectively included in this study. The Spondyloarthritis Research Consortium of Canada sacroiliac joint inflammation score (SIS) and structural score (SSS) were used to evaluate the acute and chronic lesions in the SIJs. Scores representing the distribution of bone marrow edema, fatty lesions and erosions were extracted respectively. By dividing the SIJs into sacral or iliac sections, upper or lower sections, anterior and posterior levels, differences of scores representing acute and chronic lesions were analyzed by Kruskal Wallis' tests. SIS scores were not significantly different in sacral or iliac sections, in upper or lower sections, on anterior or posterior levels. SSS scores were also not significantly different in different sections, except for higher occurrence rates of erosions in the iliac sections. Post-hoc analysis showed that there was a higher erosion score in the left ilium than left sacrum, as well as in right ilium than left sacrum. There was no specific distribution pattern of acute or chronic lesions in the SIJs in patients with axSpA. A bigger study sample was needed to confirm the distribution of erosions in sacral or iliac sections.

BackgroundFindings of fatty lesions in the context of other imaging manifestations, especially bone marrow edema and erosions can effectively assist in the diagnosis of axSpA. Chemical shift-encoded MRI is a sequence which allows for the quantification of fat signal and has been applied in the imaging evaluation of the SIJ in axSpA. The objective of this study was to investigate the diagnostic performance of morphological features of fatty lesions visualized by CSE-MRI in the imaging evaluation of SIJ in axSpA.MethodsFatty lesions with morphological features (subchondral, homogeneity and distinct border) were assessed and recorded as a binary variable in each quadrant of the SIJ. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for different morphological features as well as the anatomical distribution in patients with nr-axSpA and r-axSpA. T1-weighted images and CSE-MRI fat fraction maps were directly compared in the recognition of different morphological features.ResultsEighty-two patients [non-SpA ( n  = 21), nr-axSpA ( n  = 23), r-axSpA ( n  = 38)] with lower back pain (LBP) were enrolled. Presence of the three morphological features of fatty lesions had a specificity of 90.48% in axSpA. The sensitivities of being subchondral, homogeneity and distinct border were 52.17, 39.13 and 39.13% in nr-axSpA on T1-weighted images. For patients with r-axSpA, the sensitivities reached 86.84, 76.32 and 57.89%. No significant difference was found in the distribution of fatty lesions between T1-weighted images and CSE-MRI. However, CSE-MRI fat fraction maps could detect significantly more fatty lesions with homogeneity ( p  = 0.0412) and distinct border ( p  = 0.0159) than T1-weighted images in the sacroiliac joint, but not subchondral lesions ( p  = 0.6831).ConclusionThe homogeneity and distinct border are more relevant for the diagnosis of axSpA. Moreover, CSE-MRI could detect more typical morphological features of fatty lesions than T1-weighted images in showing these two features. The presence of all three features was more likely to be indicative of axSpA.

Background This study aimed to investigate the accuracy of identifying enthesitis along with other inflammatory lesions and structural lesions on the MRI of the sacroiliac joints (SIJ) by readers of varying experience and how training sessions and workshops could help improve the accuracy. Methods A total of 224 patients with clinical diagnosis of axial spondyloarthritis who underwent SIJ MRI examinations were retrospectively included in this study. Three readers with 5 years, 3 years and 1 year of experience in musculoskeletal imaging were invited to review the SIJ MRI images independently, while the imaging reports of a senior radiologist (> 10 years’ experience) were used as reference. After the first round of image review, a training session and a workshop on the imaging of SIJ in spondyloarthritis were held and the three readers were asked to review the images in the second round. We calculated the accuracy of identifying inflammatory and structural lesions of the three readers as well as the intra-reader agreement. Results Enthesitis could be observed in 52.23% of the axial spondyloarthritis patients, while 81.58% of the patients with enthesitis were accompanied with bone marrow edema. All the three readers showed better accuracy at identifying structural lesions than inflammatory lesions. In the first round of image review, the three readers only correctly identified 15.07%, 2.94% and 0.74% of the enthesitis sites. After the training session and workshop, the accuracy rose to 61.03%, 39.34% and 20.22%. The intra-reader agreement of enthesitis calculated as Cohen’s kappa was 0.23, 0.034 and 0.014, respectively. Conclusion Readers with less experience in musculoskeletal imaging showed lower accuracy of identifying inflammatory lesions, notably enthesitis. Training sessions and workshops could help improve the diagnostic accuracy of the junior readers.