Early Diagnosis Of Ankylosing Spondylitis Research Articles

A Cost-Effective and Labor-Saving Method for Detecting Human Leukocyte Antigen B27 Status via Sequence-Encoded Fluorescence Amplification Assay

Identification of Human leukocyte antigen B27 (HLA-B27) by flow cytometry (FCM) has been widely applied in clinical practice for auxiliary diagnosis of ankylosing spondylitis (AS). However, FCM requires fresh-prepared samples and relies on expensive equipment, reagents, and experienced operator. To provide a cheaper and more convenient method for HLA-B27 detection, we proposed a new method termed sequence-encoded fluorescence amplification assay (SEFA), which specially recognized sequences of HLA-B27 gene (HLA-B*27) covering current common subtypes in a single closed tube. SEFA could detect as low as 10 pg (equals to 3 copies) genomic DNA (gDNA) per reaction and distinguish HLA-B*27 from other HLA-B alleles with highly similar sequences. A total of 288 clinical samples were tested by SEFA, including 181 AS patients and 107 healthy controls. Compared with the detection results from FCM, two controversial samples of AS patients were obtained and further confirmed to be consistent with SEFA by sanger sequencing, indicating that our method was more accurate than FCM. Moreover, SEFA could detect HLA-B27 status by using supernatant from crude extract of 10-μL blood without commercial reagents. Overall, SEFA has the potential to be an alternative for HLA-B27 identification with the advantage of convenience and low-cost, especially suitable for early diagnosis of AS in areas with limited medical resources.

Ultrasound characteristics of soft tissues near sacroiliac joints and in the lumbar region of patients with ankylosing spondylitis.

To investigate the musculoskeletal morphomechanical properties (i.e., the thickness and elastic modulus) and the total count of power Doppler signals near the sacroiliac joints in patients with ankylosing spondylitis (AS) and non-AS individuals. Twenty participants with AS [median age (interquartile range): 31.7 (11.04) years] and 19 controls [36.3 (10.5) years] with no AS history were recruited. Bilateral ultrasound image acquisition was performed, including the short posterior sacroiliac ligament, interosseous sacroiliac ligament, long posterior sacroiliac ligament, iliolumbar ligament, proximal piriformis muscle, and sacrotuberous ligament. The intraclass correlation coefficients (ICC) of ultrasound parameters, laboratory test results of human leukocyte antigen B27, C-reactive protein, and erythrocyte sedimentation rate, and self-reported physical and disease activity scores were also obtained. The ligaments and piriformis muscle were thicker and stiffer (greater elastic modulus) in participants with AS than in non-AS participants (all p<0.01). The measurements showed good or excellent reliability (all ICC(3,1) >0.85). The numbers of power Doppler signals detected in the iliolumbar ligament, proximal piriformis muscle, and sacrotuberous ligament were higher in participants with AS than in non-AS participants (all p<0.001). A correlation was identified between disease duration and the elastic modulus of the piriformis muscle (r=0.640, p=0.003). We conclude that the ligaments and proximal piriformis muscle of AS participants have increased thickness, elastic modulus, and power Doppler signal than those of non-AS individuals. These reliable findings may serve as potential markers for the early diagnosis of AS and for assessing medication effects.

ASNET: A Novel AI Framework for Accurate Ankylosing Spondylitis Diagnosis from MRI.

Ankylosing spondylitis (AS) is a chronic, painful, progressive disease usually seen in the spine. Traditional diagnostic methods have limitations in detecting the early stages of AS. The early diagnosis of AS can improve patients' quality of life. This study aims to diagnose AS with a pre-trained hybrid model using magnetic resonance imaging (MRI). In this research, we collected a new MRI dataset comprising three cases. Furthermore, we introduced a novel deep feature engineering model. Within this model, we utilized three renowned pretrained convolutional neural networks (CNNs): DenseNet201, ResNet50, and ShuffleNet. Through these pretrained CNNs, deep features were generated using the transfer learning approach. For each pretrained network, two feature vectors were generated from an MRI. Three feature selectors were employed during the feature selection phase, amplifying the number of features from 6 to 18 (calculated as 6 × 3). The k-nearest neighbors (kNN) classifier was utilized in the classification phase to determine classification results. During the information phase, the iterative majority voting (IMV) algorithm was applied to secure voted results, and our model selected the output with the highest classification accuracy. In this manner, we have introduced a self-organized deep feature engineering model. We have applied the presented model to the collected dataset. The proposed method yielded 99.80%, 99.60%, 100%, and 99.80% results for accuracy, recall, precision, and F1-score for the collected axial images dataset. The collected coronal image dataset yielded 99.45%, 99.20%, 99.70%, and 99.45% results for accuracy, recall, precision, and F1-score, respectively. As for contrast-enhanced images, accuracy of 95.62%, recall of 80.72%, precision of 94.24%, and an F1-score of 86.96% were attained. Based on the results, the proposed method for classifying AS disease has demonstrated successful outcomes using MRI. The model has been tested on three cases, and its consistently high classification performance across all cases underscores the model's general robustness. Furthermore, the ability to diagnose AS disease using only axial images, without the need for contrast-enhanced MRI, represents a significant advancement in both healthcare and economic terms.

Current health resources required for the management of ankylosing spondylitis in developing areas of China.

Current health resources required for the management of ankylosing spondylitis in developing areas of China.

Untargeted Lipidomics Reveals Characteristic Biomarkers in Patients with Ankylosing Spondylitis Disease.

Objective. Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton. Early and accurate diagnosis is necessary for the timely and effective treatment of this disease and its common complications. Lipid metabolites form various kinds of bioactive molecules that regulate the initiation and progression of inflammation. However, there are currently few studies that investigate the alteration of serum lipid in AS patients. Methods. Blood samples were collected from 115 AS patients and 108 healthy controls (HCs). Serum-untargeted lipidomics were performed using ultrahigh-performance liquid chromatography coupled with Q-Exactive spectrometry, and the data were determined by multivariate statistical methods to explore potential lipid biomarkers. Results. Lipid phenotypes associated with disease activity were detected in the serum of patients with AS. Of all 586 identified lipids, there are 297 differential lipid metabolites between the AS and HC groups, of which 15 lipid metabolites are significant. In the AS groups, the levels of triacylglycerol (TAG) (18:0/18:1/20:0) were increased, and the levels of phosphatidylcholine (PC) (16:0e/26:4) and PC (18:1/22:6) were decreased. The areas under the receiver operating characteristic curve (AUC) of TAG (18:0/18:1/20:0), PC (16:0e/26:4), and PC (18:1/22:6) were 0.919, 0.843, and 0.907, respectively. Conclusion. Our findings uncovered that lipid deregulation is a crucial hallmark of AS, thereby providing new insights into the early diagnosis of AS.

Novel peripheral blood diagnostic biomarkers screened by machine learning algorithms in ankylosing spondylitis.

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disorder of unknown etiology that is hard to diagnose early. Therefore, it is imperative to explore novel biomarkers that may contribute to the easy and early diagnosis of AS. Methods: Common differentially expressed genes between normal people and AS patients in GSE73754 and GSE25101 were screened by machine learning algorithms. A diagnostic model was established by the hub genes that were screened. Then, the model was validated in several data sets. Results: IL2RB and ZDHHC18 were screened using machine learning algorithms and established as a diagnostic model. Nomograms suggested that the higher the expression of ZDHHC18, the higher was the risk of AS, while the reverse was true for IL2RB in vivo. C-indexes of the model were no less than 0.84 in the validation sets. Calibration analyses suggested high prediction accuracy of the model in training and validation cohorts. The area under the curve (AUC) values of the model in GSE73754, GSE25101, GSE18781, and GSE11886 were 0.86, 0.84, 0.85, and 0.89, respectively. The decision curve analyses suggested a high net benefit offered by the model. Functional analyses of the differentially expressed genes indicated that they were mainly clustered in immune response-related processes. Immune microenvironment analyses revealed that the neutrophils were expanded and activated in AS while some T cells were decreased. Conclusion: IL2RB and ZDHHC18 are potential blood biomarkers of AS, which might be used for the early diagnosis of AS and serve as a supplement to the existing diagnostic methods. Our study deepens the insight into the pathogenesis of AS.

Noncoding RNAs Involved in the Pathogenesis of Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a form of arthritis that can lead to fusion of vertebrae and sacroiliac joints following syndesmophyte formation. The etiology of this painful disease remains poorly defined due to its complex genetic background. There are no commonly accepted methods for early diagnosis of AS, nor are there any effective or efficient clinical treatments. Several noncoding RNAs (ncRNAs) have been linked to AS pathogenesis and inflammation via selective binding of their downstream targets. However, major gaps in knowledge remain to be filled before such findings can be translated into clinical treatments for AS. In this review, we outline recent findings that demonstrate essential roles of ncRNAs in AS mediated via multiple signaling pathways such as the Wnt, transforming growth factor-β/bone morphogenetic protein, inflammatory, T-cell prosurvival, and nuclear factor-κB pathways. The summary of these findings provides insight into the molecular mechanisms by which ncRNAs can be targeted for AS diagnosis and the development of therapeutic drugs against a variety of autoimmune diseases.

MicroRNA implications in the etiopathogenesis of ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease that affects both axial and peripheral skeletons as well as soft tissues. Recent investigations offer that disease pathogenesis is ascribed to a complex interplay of genetic, environmental, and immunological factors. Until now, there is no appropriate method for early diagnosis of AS and the successful available therapy for AS patients stay largely undefined. MicroRNAs (miRNAs), endogenous small noncoding RNAs controlling the functions of target mRNAs and cellular processes, are present in human plasma in a stable form and have appeared as possible biomarkers for activity, pathogenesis, and prognosis of the disease. In the present review, we have tried to summarize the recent findings related to miRNAs in AS development and discuss the possible utilization of these molecules as prognostic biomarkers or important therapeutic strategies for AS. Further examinations are needed to determine the unique miRNAs signatures in AS and characterize the mechanisms mediated by miRNAs in the pathology of this disease.

Sacroiliitis mimics: a case report and review of the literature

BackgroundRadiographic sacroiliitis is the hallmark of ankylosing spondylitis (AS), and detection of acute sacroiliitis is pivotal for early diagnosis of AS. Although radiographic sacroiliitis is a distinguishing feature of AS, sacroiliitis can be seen in a variety of other disease entities.Case presentationWe present an interesting case of sacroiliitis in a patient with Paget disease; the patient presented with inflammatory back pain which was treated with bisphosphonate. This case demonstrates comorbidity with Paget disease and possible ankylosing spondylitis. We also present a review of the literature for other cases of Paget involvement of the sacroiliac joint.ConclusionsIn addition, we review radiographic changes to the sacroiliac joint in classical ankylosing spondylitis as well as other common diseases. We compare and contrast features of other diseases that mimic sacroiliitis on a pelvic radiograph including Paget disease, osteitis condensans ilii, diffuse idiopathic skeletal hyperostosis, infections and sarcoid sacroiliitis. There are some features in the pelvic radiographic findings which help distinguish among mimics, however, one must also rely heavily on extra-pelvic radiographic lesions. In addition to the clinical presentation, various nuances may incline a clinician to the correct diagnosis; rheumatologists should be familiar with the imaging differences among these diseases and classic spondylitis findings.

Detection of novel diagnostic antibodies in ankylosing spondylitis: An overview.

Ankylosing spondylitis (AS) is a debilitating, chronic, rheumatic disease characterized by inflammation and new bone formation resulting in fusion of the spine and sacroiliac joints. Since early treatment is impeded by a delayed diagnosis, it is highly important to find new biomarkers that improve early diagnosis and may also contribute to a better assessment of disease activity, prognosis and therapy response in AS. Because of the absence of rheumatoid factor, AS was long assumed to have a seronegative character and antibodies are thus not considered a hallmark of the disease. However, emerging evidence suggests plasma cells and autoantibodies to be involved in the disease course. In this review, the role of B cells and antibodies in AS is discussed. Furthermore, an overview is provided of antibodies identified in AS up till now, and their diagnostic potential. Many of these antibody responses were based on small study populations and further validation is lacking. Moreover, most were identified by a hypothesis-driven approach and thus limited to antibodies against targets that are already known to be involved in AS pathogenesis. Hence, we propose an unbiased approach to identify novel diagnostic antibodies. The already successfully applied techniques cDNA phage display and serological antigen selection will be used to identify antibodies against both known and new antigen targets in AS plasma. These newly identified antibodies will enhance early diagnosis of AS and provide more insight into the underlying disease pathology, resulting in a more effective treatment strategy and eventually an improved disease outcome.

Delayed diagnosis of ankylosing spondylitis in a Japanese population

Objectives: This study was conducted to evaluate the period from symptom onset to diagnosis of ankylosing spondylitis (AS) in Japanese patients and to examine possible reasons for delayed diagnosis.Methods: Seventy-two consecutive patients with AS were studied. Diagnostic delay was defined as the gap between the first spondyloarthropathic symptom and diagnosis of AS according to the modified New York criteria.Results: The mean patient ages at disease onset and diagnosis were 25.6 ± 11.3 and 33.3 ± 13.2 years old, respectively, resulting in diagnostic delay of 6.7 years. The number of medical institutions to which patients were referred before diagnosis was 2.4, and orthopedic surgeons were most commonly visited (62%). Non-specific low back pain or lumbar spondylitis (33%) and degenerative arthritis (28%) were the primary diagnoses preceding that of AS. Absence of articular symptoms significantly correlated with diagnostic delay. The patients with disease onset on year 2000 or later had significantly shorter periods until diagnosis than those before 2000 (3.6 vs. 7.5 years).Conclusions: The present study showed a marked diagnostic delay among Japanese patients with AS. Although it has been improved, continuing medical education focusing on inflammatory back pain in adolescent is required for early diagnosis of AS.

EFFECTIVENESS OF EDUCATIONAL PROGRAMS ON EARLY DIAGNOSIS OF ANKYLOSING SPONDYLITIS FOR PRIMARY CARE PHYSICIANS IN KAZAN

The diagnosis of ankylosing spondylitis (AS) in the real-life practice is delayed for 7–8 years on average. Educational programs for primary care physicians may promote the disease diagnosis. Objective. To analyze the effectiveness of the educational programs for the early diagnosis of AS for primary contact physicians in the real-life clinical practice in Kazan. Material and methods. The development of the educational programs and determination of their effectiveness com- prised three stages: 1) determination of the level of knowledge and problems in the diagnosis and treatment of AS among primary care physicians and neurologists; 2) development of educational programs suitable to be used in the real-life clinical practice; 3) analysis of the effectiveness of implementing the programs according to the reports on work of the City Rheumatology Center in 2009–2011. Results. After running the courses, the number of patients with AS at the Kazan City Rheumatology Center increased almost twofold, from 378 in 2009 to 683 in 2011; the period from the onset of the disease to diagnosis was simultane- ously reduced from 8.4 to 3.5 years. Conclusion. The educational programs for primary care physicians and neurologists in Kazan have promoted shorten- ing of the AS diagnosis time.

Analysis of the effect of the oral contraceptive pill on clinical outcomes in women with ankylosing spondylitis.

There are unexplained sex-specific changes in the clinical expression of ankylosing spondylitis (AS). We sought to examine the potential effect of exogenous estrogen in the form of oral contraceptive pills (OCP) on AS initiation and severity. This cross-sectional study consisted of women with AS from the membership of the Spondylitis Association of America. Measures of disease severity included use of biological agents and hip replacement surgery, while Bath AS Functional Index (BASFI) scores served as a surrogate marker of disability. Information was obtained using a patient questionnaire on patient demographics, OCP use, pregnancy history, AS duration, medication use, and hip replacement. There were 571 women with AS who participated in our study, consisting of 448 OCP ever-users and 123 non-OCP users. The mean age of OCP users was 42.7 yrs (± 11.5) and of non-OCP users, 48.4 yrs (± 12.1). No difference was noted in the age at initial onset of back pain. However, OCP users were significantly younger at the time of diagnosis of AS (36.5 yrs vs 39.1 yrs, p = 0.02). There were no significant differences between the 2 groups in tumor necrosis factor inhibitor or opioid use, BASFI scores, pregnancy complications, or hip surgery. The use of exogenous estrogens in the form of OCP is not associated with a measurable effect on initiation or severity of AS. Biologic and social factors may contribute to earlier diagnosis of AS in OCP users. This is the largest study to date investigating the potential effect of exogenous estrogens in women with AS.

PC0004 Educational programs for physicians in diagnosis and treatment of ankylosing spondylitis in kazan (russia)

BackgroundAt present, the average time interval between appearance of the first signs of ankylosing spondylitis (AS) and the correct diagnosis is 7-8 years. This fact leads to delay of potentially...

AB0809 Educational programs for primary care physicians - effectiveness in diagnosis and treatment of ankylosing spondylitis in kazan

BackgroundThe long period of time from the first signs of ankylosing spondylitis (AS) to the correct diagnosis (mean 7-8 years) presents a delay of potentially effective therapy.ObjectivesTo evaluate the effectiveness...

Ankylosing spondylitis morbidity trends in Russia and Saturday spondyloarthritis schools

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Oral abstracts 1: Spondyloarthropathies * O1. Detecting axial spondyloarthritis amongst primary care back pain referrals

Background: Inflammatory back pain (IBP) is an early feature of ankylosing spondylitis (AS) and its detection offers the prospect of early diagnosis of AS. However, since back pain is very common but only a very small minority of back pain sufferers have ASpA or AS, screening of back pain sufferers for AS is problematic. In early disease radiographs are often normal so that fulfilment of diagnostic criteria for AS is impossible though a diagnosis of axial SpA can be made if MRI evidence of sacroiliitis is present. This pilot study was designed to indicate whether a cost-effective pick up rate for ASpA/early AS could be achieved by identifying adults with IBP stratified on the basis of age. Methods: Patients aged between 18 and 45 years who were referred to a hospital physiotherapy service with back pain of more than 3 months duration were assessed for IBP. All were asked to complete a questionnaire based on the Berlin IBP criteria. Those who fulfilled IBP criteria were also asked to complete a second short questionnaire enquiring about SpA comorbidities, to have a blood test for HLA-B27 and CRP level and to undergo an MRI scan of the sacroiliac joints. This was a limited scan, using STIR, diffusion-weighted, T1 and T2 sequences of the sacroiliac joints to minimize time in the scanner and cost. The study was funded by a research grant from Abbott Laboratories Ltd. Results: 50 sequential patients agreed to participate in the study and completed the IBP questionnaire. Of these 27 (54%) fulfilled criteria for IBP. Of these, 2 patients reported a history of an SpA comorbidity - 1 psoriasis; 1 ulcerative colitis - and 3 reported a family history of an SpA comorbidity - 2 psoriasis; 1 Crohn’s disease. 4 were HLA-B27 positive, though results were not available for 7. Two patients had marginally raised CRP levels (6, 10 -NR ≤ 5). 19 agreed to undergo MRI scanning of the sacroiliac joints and lumbar spine; 4 scans were abnormal, showing evidence of bilateral sacroiliitis on STIR sequences. In all cases the changes met ASAS criteria but were limited. Of these 4 patients 3 were HLA-B27 positive but none gave a personal or family history of an SpA-associated comorbidity and all had normal CRP levels. Conclusions: This was a pilot study yielding only limited conclusions. However, it is clear that: Screening of patients referred for physiotherapy for IBP is straightforward, inexpensive and quick. It appears that IBP is more prevalent in young adults than overall population data suggest so that targeting this population may be efficient. IBP questionnaires could be administered routinely during a physiotherapy assessment. HLA-B27 testing in this group of patients with IBP is a suitable screening tool. The sacroiliac joint changes identified were mild and their prognostic significance is not yet clear so that the value of early screening needs further evaluation. Disclosure statement: C.H. received research funding for this study from Abbott. A.K. received research funding for this study, and speaker and consultancy fees, from Abbott. All other authors have declared no conflicts of interest.

Value of diffusion-weighted magnetic resonance imaging in early diagnosis of ankylosing spondylitis

The objective of this study is to estimate the value of diffusion-weighted MRI (DWI) in the detection of abnormalities in sacroiliac joints in the patients with early ankylosing spondylitis (AS) and investigate the feasibility of whole-body DWI (WB-DWI) in systemic evaluation of AS. Sixteen patients with early AS, 18 patients with simple low back pain (LBP), and 18 healthy volunteers were involved in this study. All subjects underwent conventional MRI and DWI. Apparent diffusion coefficient (ADC) in subchondral bone marrows of sacroiliac joints was measured. Independent-sample t test was used to statistically analyze the difference of ADC values between groups. WB-DWI was performed in additional 12 patients with clinically confirmed AS. The image results were analyzed by multiple post-processing techniques, as compared to conventional MRI. In AS patients, mean ADC values were (0.494 ± 0.170) × 10(-3) mm(2)/s in sacrum and (0.513 ± 0.129) × 10(-3) mm(2)/s in ilium, which were significantly higher than those of LBP ((0.306 ± 0.057) × 10(-3) mm(2)/s in sacrum and (0.323 ± 0.083) × 10(-3) mm(2)/s in ilium) and healthy volunteers ((0.315 ± 0.009) × 10(-3) mm(2)/s in sacrum and (0.319 ± 0.012) × 10(-3) mm(2)/s in ilium). No statistical differences were found between simple LBP and healthy volunteers. Mean ADC value of multiple lesions in AS was (0.932 ± 0.299) × 10(-3) mm(2)/s. By WB-DWI, abnormal signals of sacroiliac joints and extra-sacroiliac joint lesions were demonstrated in the locations corresponding with clinical findings. Mean ADC values of multiple lesions were (1.298 ± 0.323) × 10(-3) mm(2)/s in sacrum and (1.216 ± 0.311) × 10(-3) mm(2)/s in ilium. DWI and WB-DWI were shown to be effective in differentiation and systemic evaluation of early AS. Both techniques are likely to play an importance role in the early diagnosis of AS and assessment of treatment response.

Significance of sacroiliac joint aerocele in diagnosis of ankylosing spondylitis

To explore the significance of sacroiliac joint aerocele in the diagnosis of ankylosing spondylitis, the data of 196 patients with ankylosing spondylitis (AS) were collected during December of 2008 to May of 2009. And 50 patients with osteoarthritis (OA), 15 patients with sclerosing osteitis (SO) and 47 patients with sacroiliac joint tumors were investigated as the control groups. The feature of sacroiliac joint aerocele in computed tomography (CT) images was observed carefully. In AS group there were 130 patients (66.3%) diagnosed as AS according to CT results, and 32 of them (24.6%) were observed with aerocele within sacroiliac joint cavity, majority of whom were earlier AS patients with slight bone destruction. Other 66 patients were diagnosed as early AS according to magnetic resonance imaging (MRI) and ultrasonography. CT examination showed that the 66 patients did not have apparent bone destruction, of whom, 26 (39.4%) patients had aerocele within sacroiliac joint cavity. Among the control groups of 15 (15/50, 30.0%) patients with OA, 5 (5/15, 33.3%) patients with SO were observed sacroiliac joint aerocele. The 47 patients with sacroiliac joint tumors were observed with bone or cartilage destruction, but without signs of sacroiliac joint aerocele. The sacroiliac joint aerocele in CT images of AS patients usually appeared as spots, streaks, small or larger round blocks, and it often happened in patients with earlier stage of diseases. Sacroiliac joint aerocele may be useful to early diagnosis of AS.

Research progress in the relationship between HLA-B27 and ankylosing spondylitis

Background Ankylosing Spondylitis (AS) is a common autoimmune joint disease, which mostly occurs to young men. Early diagnose of AS is difficult and the treatment is not satisfactory at present. Studies have been released that there is a strong relationship bewteen Human leucocyte antigen-B27 (HLA-B27). It is estimated that 90% AS patients were HLA-B27 positive, which was thought of vital importance for early diagnosis of AS. Objective This paper will review the relationship between AS and HLA -B27 which would provide the base on diagnosis and treatment of AS. Content This paper focuses on AS pathogenesis, pathology and clinical manifestations to summarize the relationship and diagnosis significance between HLA -B27 and AS. Trend The HLA-B27 antigen has a high correlation with AS, which can be used as an important clinical indicator for early diagnosis of AS. However it should be mentioned that any exaggeration of the role of HLA-B27 in the diagnosis of AS should be avoided, particular in HLA-B27 negative patients. Key words: Ankylosing spondylitis; HLA-B27 Antigen