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1.
BMC Musculoskelet Disord ; 25(1): 361, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714989

ABSTRACT

BACKGROUND: Identifying remission is of high importance in rheumatoid arthritis (RA) because remission is associated with less structural progression. We investigated the efficacy of a new optical imaging device, HandScan, to identify RA remission, as defined by ultrasound (US). METHODS: 61 RA patients were included. Disease activity was evaluated by clinical assessment and US, using gray-scale (GS) and Power Doppler (PD). HandScan determined unitary optical spectral transmission (OST) values for wrists, metacarpophalangeal and proximal interphalangeal joints. At the patient level, three composite HandScan (HS) scores were calculated: total HS score; disease activity score OST (DAS-OST) and DAS-OST without patient global assessment (PtGA). Using ROC curves, we determined HS cut-offs to identify US-defined remission. RESULTS: At the joint level, unitary OST values significantly correlated with GS synovitis [odds ratio (OR) 2.43, p < 0.0001] and PD positivity (OR 3.72, p = 0.0002 ). At the patient level, total HS score and DAS-OST were significantly associated with all gray-scale US (GSUS) and power doppler US (PDUS) parameters evaluated (synovitis number and grade, synovial thickness, PD grade) (p < 0.05). The cut-off to identify US-defined remission at the joint level was of 0.92, giving an 81% sensitivity and a 96% positive predictive value (PPV). At the patient level, ROC-curves failed to identify a robust cut-off for the total HS score, but did identify a cut-off (3.68) for DAS-OST to identify US-defined remission, but with lower sensitivity (75%), specificity (56%) and PPV (67%). CONCLUSIONS: HandScan is a non-invasive optical imaging technique providing OST values that correlate with GSUS and PDUS parameters. In addition, HandScan is able to reliably identify US-defined remission in RA at the joint level, with a good sensitivity and high PPV. At the patient level, HandScan DAS-OST can also determine US remission (while total HS score failed to do so), but with lower performance.


Subject(s)
Arthritis, Rheumatoid , Remission Induction , Ultrasonography, Doppler , Humans , Arthritis, Rheumatoid/diagnostic imaging , Male , Female , Middle Aged , Aged , Ultrasonography, Doppler/methods , Adult , Optical Imaging/methods , Severity of Illness Index
2.
J Clin Med ; 13(8)2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38673536

ABSTRACT

Hypophosphatasia is a rare genetic disease characterized by abnormal alkaline phosphatase activity and deficiency of bone and teeth mineralization. Hypophosphatasia is well known in pediatrics with typical presentations in children, but mild forms can also be present in adults and are difficult to detect. We present the case of a 50-year-old woman referred for pain management, with a previous diagnosis of fibromyalgia. The association of clinical features (diffuse pain syndrome, early dental loosening, personal history of two fractures with osteoporosis, and family history of osteoporosis) with radiographic (heterotopic calcifications of the yellow and interspinous lumbar ligaments) and biological (low levels of total alkaline phosphatase) indices was suggestive of hypophosphatasia, which was confirmed by genetic analysis. We review and discuss the association between hypophosphatasia, musculoskeletal pain, and calcium pyrophosphate deposition and the importance of raising the diagnosis of adult-onset hypophosphatasia when facing these two rheumatologic entities.

3.
Rev Med Liege ; 78(12): 733-739, 2023 Dec.
Article in French | MEDLINE | ID: mdl-38095039

ABSTRACT

We describe the case of a patient with a history of gout, who presents with a new episode of acute gout. Based on this clinical case, we will discuss the management of acute gout. We will then address the management of chronic gout, i.e., the indications for a hypouricemic treatment and the caution required when starting this treatment. Finally, we will address the need for a holistic care, discussing the change of certain co-medications, screening for cardiovascular comorbidities and providing diet and life-style recommendations.


Nous décrivons le cas d'un patient, goutteux connu, qui présente un nouvel accès aigu. Nous discutons tout d'abord, à partir de ce cas clinique, la prise en charge aiguë de la crise de goutte. Nous abordons ensuite les indications de mise en place d'un traitement de fond hypo-uricémiant et les précautions à prendre lors de cette introduction. Enfin, nous détaillons la prise en charge holistique, en évoquant les modifications de certaines thérapeutiques, le dépistage des comorbidités cardiovasculaires et les conseils hygiéno-diététiques.


Subject(s)
Gout , Hyperuricemia , Humans , Hyperuricemia/diagnosis , Hyperuricemia/drug therapy , Gout/therapy , Gout/drug therapy , Life Style , Comorbidity , Gout Suppressants/therapeutic use
4.
Rev Med Liege ; 78(11): 626-633, 2023 Nov.
Article in French | MEDLINE | ID: mdl-37955292

ABSTRACT

The Ehlers Danlos syndromes (EDS) are a heterogenous group of inherited connective tissue disorders characterized by generalized joint hypermobility and instability, tissue fragility and multiple functional disorders. The EDS hypermobility type (hEDS) is the most common but the mildest subtype of EDS and is defined by joint involvement. hSED diagnosis is based on clinical criteria because no genetic factors nor molecular basis have yet been identified. Since chronic pain constitutes one of hESD main symptoms, the diagnosis is frequently suspected although the syndrome is rare, with a prevalence estimated to be 1/10.000. An expert clinical evaluation is therefore necessary in order to establish an accurate diagnosis. This allows the implementation of physical therapy which is the only treatment that has proven efficacious in reducing joint instability, generalized pain and secondary osteoarthritis.


Les syndromes d'Ehlers Danlos (SED) sont un groupe hétérogène de maladies héréditaires du tissu conjonctif, caractérisées par une hypermobilité et une instabilité articulaires généralisées, une fragilité des tissus et de multiples troubles fonctionnels. La forme hypermobile du SED (hSED) est le sous-type le plus fréquent, mais le moins sévère des SED. Elle se présente essentiellement sous forme de manifestations articulaires. Le diagnostic du hSED repose sur des critères cliniques, aucun facteur génétique ni base moléculaire n'ayant été identifiés à ce jour. La douleur chronique étant l'un des symptômes principaux du hSED, le diagnostic est souvent évoqué alors que le syndrome est rare, la prévalence étant estimée à 1/10.000. Une expertise clinique est nécessaire afin d'établir un diagnostic correct. Ceci permet la mise en route d'une rééducation kinésithérapique, seul traitement ayant démontré son efficacité pour contrôler les symptômes et réduire l'instabilité articulaire et l'arthrose secondaire.


Subject(s)
Connective Tissue Diseases , Ehlers-Danlos Syndrome , Joint Instability , Skin Abnormalities , Humans , Rare Diseases/complications , Ehlers-Danlos Syndrome/diagnosis , Ehlers-Danlos Syndrome/therapy , Ehlers-Danlos Syndrome/complications , Connective Tissue Diseases/complications , Skin Abnormalities/complications , Pain/complications , Joint Instability/diagnosis , Joint Instability/therapy , Joint Instability/complications
5.
Rev Med Liege ; 78(11): 641-648, 2023 Nov.
Article in French | MEDLINE | ID: mdl-37955294

ABSTRACT

Rheumatoid arthritis is a chronic inflammatory systemic disease. Pulmonary manifestations are the most common extra-articular involvements and can impact all components of the respiratory system: parenchyma, pleura, vessels and airways, all complications that are briefly described in this article. Interstitial lung disease is the most common of these and is associated with significant morbidity and mortality. Its detection and monitoring are based on spirometry and thoracic imaging. Specific treatments are initiated in order to reduce the risk of disease flare up but may themselves in case of toxicity be associated with respiratory manifestations, either directly or by promoting infectious complications.


La polyarthrite rhumatoïde est une pathologie systémique inflammatoire chronique. Les manifestations pulmonaires représentent l'atteinte extra-articulaire la plus fréquente et peuvent affecter tous les composants du système respiratoire : le parenchyme, la plèvre, les vaisseaux et les voies aériennes, complications décrites brièvement dans cet article. La pneumopathie interstitielle diffuse en est la plus commune et associée à une morbi-mortalité importante. Son dépistage et son suivi reposent sur les épreuves fonctionnelles et l'imagerie thoracique. Des traitements spécifiques sont initiés afin de limiter au mieux l'évolution pulmonaire, mais peuvent eux-mêmes être associés à des manifestations respiratoires, soit directement, soit en favorisant des complications infectieuses.


Subject(s)
Arthritis, Rheumatoid , Lung Diseases, Interstitial , Lung Diseases , Humans , Lung Diseases/etiology , Lung Diseases/complications , Arthritis, Rheumatoid/complications , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/therapy
6.
Rev Med Liege ; 78(10): 586-592, 2023 Oct.
Article in French | MEDLINE | ID: mdl-37830325

ABSTRACT

We here describe the case of a post-menopausal woman presenting with a recent vertebral fracture and cortical osteopenia on bone dual energy X-ray absorptiometry. Based on this case, we will discuss the definition and diagnosis of osteoporosis as well as the indications to treat, which go beyond the densitometric-based definition of osteoporosis. We will also address the osteoporosis screening recommendations, and the blood workup required before treatment initiation. The choice of the treatment, its duration and the non-pharmacological measures will be discussed in another article.


Nous décrivons le cas d'une patiente ménopausée présentant un tassement vertébral récent et une ostéopénie corticale sur la densitométrie osseuse. Nous discutons, à partir de ce cas clinique, la définition et le diagnostic de l'ostéoporose, ainsi que les indications thérapeutiques, qui dépassent le cadre de la simple définition densitométrique. Nous abordons ensuite les indications de dépistage de l'ostéoporose, ainsi que le bilan biologique et étiologique à réaliser avant l'instauration du traitement. Le choix du traitement reminéralisateur, la durée du traitement et la prise en charge non médicamenteuse de l'ostéoporose seront discutés dans une autre vignette.


Subject(s)
Bone Diseases, Metabolic , Osteoporosis , Female , Humans , Bone Density , Osteoporosis/diagnosis , Absorptiometry, Photon
7.
Rev Med Liege ; 78(4): 239-244, 2023 Apr.
Article in French | MEDLINE | ID: mdl-37067842

ABSTRACT

Romosozumab (Evenity®) is a humanized monoclonal anti-sclerostin antibody. It represents a major breakthrough in the treatment of osteoporosis: while most treatments inhibit bone resorption, romosozumab has a dual effect, by increasing bone formation and reducing bone resorption. It is reimbursed in postmenopausal osteoporosis in patients with very high fracture risk (i.e. after a recent major fracture, occurring within two years). Its ideal use, in the therapeutic sequence for post-menopausal women, is as first line treatment in case of a recent major fracture. It is contraindicated in case of hypocalcemia and personal history of stroke or myocardial infarction.


Le romosozumab (Evenity®) est un anticorps monoclonal humanisé anti-sclérostine. Il représente une avancée majeure dans le traitement de l'ostéoporose : alors que la majorité des traitements remboursés inhibent la résorption osseuse, le romosozumab présente un effet «mixte¼, en augmentant la formation osseuse et en réduisant la résorption. Il est remboursé dans l'ostéoporose post-ménopausique chez les patientes à très haut risque fracturaire (c'est-à-dire après une fracture majeure récente, survenue dans les deux ans). Son utilisation idéale, dans la séquence thérapeutique chez la femme ménopausée, le positionne en première ligne en cas de fracture majeure récente. Il est contre-indiqué en cas d'hypocalcémie et d'antécédent personnel d'accident vasculaire cérébral ou d'infarctus du myocarde.


Subject(s)
Bone Density Conservation Agents , Bone Resorption , Osteoporosis, Postmenopausal , Humans , Female , Osteoporosis, Postmenopausal/drug therapy , Bone Density , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Bone Density Conservation Agents/pharmacology , Bone Density Conservation Agents/therapeutic use
8.
Respir Res ; 24(1): 112, 2023 Apr 15.
Article in English | MEDLINE | ID: mdl-37061683

ABSTRACT

BACKGROUND: Pulmonary fibrosis is an emerging complication of SARS-CoV-2 infection. In this study, we speculate that patients with COVID-19 and idiopathic pulmonary fibrosis (IPF) may share aberrant expressed microRNAs (miRNAs) associated to the progression of lung fibrosis. OBJECTIVE: To identify miRNAs presenting similar alteration in COVID-19 and IPF, and describe their impact on fibrogenesis. METHODS: A systematic review of the literature published between 2010 and January 2022 (PROSPERO, CRD42022341016) was conducted using the key words (COVID-19 OR SARS-CoV-2) AND (microRNA OR miRNA) or (idiopathic pulmonary fibrosis OR IPF) AND (microRNA OR miRNA) in Title/Abstract. RESULTS: Of the 1988 references considered, 70 original articles were appropriate for data extraction: 27 studies focused on miRNAs in COVID-19, and 43 on miRNAs in IPF. 34 miRNAs were overlapping in COVID-19 and IPF, 7 miRNAs presenting an upregulation (miR-19a-3p, miR-200c-3p, miR-21-5p, miR-145-5p, miR-199a-5p, miR-23b and miR-424) and 9 miRNAs a downregulation (miR-17-5p, miR-20a-5p, miR-92a-3p, miR-141-3p, miR-16-5p, miR-142-5p, miR-486-5p, miR-708-3p and miR-150-5p). CONCLUSION: Several studies reported elevated levels of profibrotic miRNAs in COVID-19 context. In addition, the balance of antifibrotic miRNAs responsible of the modulation of fibrotic processes is impaired in COVID-19. This evidence suggests that the deregulation of fibrotic-related miRNAs participates in the development of fibrotic lesions in the lung of post-COVID-19 patients.


Subject(s)
COVID-19 , Idiopathic Pulmonary Fibrosis , MicroRNAs , Humans , MicroRNAs/genetics , COVID-19/genetics , COVID-19/pathology , SARS-CoV-2/genetics , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/pathology , Lung/pathology
9.
J Clin Med ; 12(6)2023 Mar 20.
Article in English | MEDLINE | ID: mdl-36983383

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Our objective is to determine if functional indices associated with emphysema on pulmonary function tests (DLCO-diffusion capacity of the lung for CO-; DLCO/AV-DLCO corrected for alveolar volume- and TLC-total lung capacity), considered alone or together, can identify COPD patients with osteoporosis. METHODS: 90 COPD patients underwent dual-energy X-ray absorptiometry (DEXA) and pulmonary function tests. RESULTS: 26% of the COPD patients were osteoporotic. In univariate analysis, each functional parameter associated with emphysema, analyzed separately, was not associated with osteoporosis. In contrast, patients with hyperinflation associated with impaired diffusion capacity and transfer coefficient, defined by the association of the three functional indices (DLCO < 70%, DLCO/AV < 80% and CPT > 115%), had significantly more osteoporosis at the total hip (OR: 5.9, CI: 1.5-23.8, p = 0.013). In multivariate analysis, this phenotype was confirmed as an independent factor associated with hip osteoporosis. In contrast, COPD airway obstruction severity, based on FEV1 (%), was not associated with osteoporosis. A lower BMI, female gender and age were also identified as osteoporosis risk factors. CONCLUSIONS: COPD patients with hyperinflation associated with impaired diffusion capacity and transfer coefficient are at higher risk for osteoporosis. Pulmonary function tests associated with emphysema detection can help to identify COPD patients with osteoporosis, in addition to the classical risk factors.

11.
Aliment Pharmacol Ther ; 50(11-12): 1204-1213, 2019 12.
Article in English | MEDLINE | ID: mdl-31650573

ABSTRACT

BACKGROUND: Spondyloarthritis is the most frequent extra-intestinal manifestation of IBD. AIM: To present simple strategies to identify and differentiate inflammatory joint pain in IBD patients. METHODS: A panel of Belgian gastroenterologists and rheumatologists developed seven algorithms for IBD patients with joint symptoms based on a Delphi exercise conducted between April and December 2016. Here, we focus on referral strategies for patients with chronic back pain (evidence-based strategy), large joint monoarthritis, oligo- or polyarticular arthritis or arthralgia (based on expert opinion). We also present management tools for IBD patients with acute back pain and small joint monoarthritis (Supplementary file). RESULTS: The reported algorithm for IBD patients with chronic back pain uses basic clinical criteria to identify which patients should be referred to the emergency room (spondylodiscitis), physical medicine and rehabilitation (mechanical back pain) or rheumatologist (spondyloarthritis). IBD patients with large joint monoarthritis should be referred to emergency room if septic arthritis is suspected; in other patients, blood analyses and referral to a rheumatologist for articular puncture with evacuation of synovial fluid are recommended. The analysis of synovial fluid allows for identification of non-inflammatory (e.g., osteoarthritis) and inflammatory (e.g., [pseudo]-gout, peripheral spondyloarthritis and Borrelia burgdorferi arthritis) conditions. In patients with inflammatory oligoarticular or polyarticular arthralgia, erythrocyte sedimentation rate, concomitant therapies, anti-nuclear factor and anti-double-stranded DNA antibody levels should be evaluated; in anti-tumour necrosis factor-treated patients, a drug-induced lupus-like syndrome should be considered. CONCLUSION: We propose straightforward strategies for IBD patients with joint symptoms, which are specific enough to select initial treatment and referral pattern.


Subject(s)
Algorithms , Back Pain/drug therapy , Chronic Pain/drug therapy , Inflammatory Bowel Diseases/drug therapy , Joint Diseases/drug therapy , Consensus , Humans , Referral and Consultation
12.
AJR Am J Roentgenol ; 205(2): 364-70, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26204289

ABSTRACT

OBJECTIVE: The purpose of this study was to compare tomosynthesis with radiography for the detection of bone erosions of the foot in patients with established rheumatoid arthritis (RA) using MDCT as a reference standard. SUBJECTS AND METHODS: Eighteen consecutive patients with established RA were included. Each patient underwent radiography, tomosynthesis, and CT examinations of the feet on the same day. Two radiologists independently determined the number of bone erosions and the Sharp-van der Heijde score with each of the three imaging modalities. RESULTS: On a total of 216 joints from 18 patients, 216 bone erosions were detected on CT, 215 on tomosynthesis, and 181 with radiography. The mean (± SD) Sharp-van der Heijde score was equivalent for tomosynthesis (18.8 ± 16.8) and CT (19.8 ± 18.5) but was statistically lower for radiography (16.4 ± 18.0) (p = 0.030). The respective overall sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for tomosynthesis were 80%, 75%, 78%, 76%, and 80%, whereas the respective corresponding values for radiography were 66%, 81%, 74%, 77%, and 71%. The radiation burden of tomosynthesis was almost equivalent to that of radiography. CONCLUSION: Tomosynthesis has a higher sensitivity than radiography to detect bone erosions of the foot in patients with established RA and imparts an almost equivalent radiation burden.


Subject(s)
Arthritis, Rheumatoid/complications , Foot Deformities, Acquired/diagnostic imaging , Radiographic Image Enhancement/methods , Female , Foot Deformities, Acquired/pathology , Humans , Male , Middle Aged , Radiographic Image Interpretation, Computer-Assisted , Sensitivity and Specificity , Tomography, X-Ray Computed
13.
Ann Rheum Dis ; 70(6): 1144-52, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21362709

ABSTRACT

OBJECTIVE: Knee osteoarthritis (OA) is a heterogeneous, complex joint pathology of unknown aetiology. Biomarkers have been widely used to investigate OA but currently available biomarkers lack specificity and sensitivity. Therefore, novel biomarkers are needed to better understand the pathophysiological processes of OA initiation and progression. METHODS: Surface enhanced laser desorption/ionisation-time of flight-mass spectrometry proteomic technique was used to analyse protein expression levels in 284 serum samples from patients with knee OA classified according to Kellgren and Lawrence (K&L) score (0-4). OA serum samples were also compared to serum samples provided by healthy individuals (negative control subjects; NC; n=36) and rheumatoid arthritis (RA) patients (n=25). Proteins that gave similar signal in all K&L groups of OA patients were ignored, whereas proteins with increased or decreased levels of expression were selected for further studies. RESULTS: Two proteins were found to be expressed at higher levels in sera of OA patients at all four K&L scores compared to NC and RA, and were identified as V65 vitronectin fragment and C3fpeptide. Of the two remaining proteins, one showed increased expression (unknown protein at m/z of 3762) and the other (identified as connective tissue-activating peptide III protein) was decreased in K&L scores >2 subsets compared to NC, RA and K&L scores 0 or 1 subsets. CONCLUSION: The authors detected four unexpected biomarkers (V65 vitronectin fragment, C3f peptide, CTAP-III and m/z 3762 protein) that could be relevant in the pathophysiological process of OA as having significant correlation with parameters reflecting local inflammation and bone remodelling, as well as decrease in cartilage turnover.


Subject(s)
Blood Proteins/analysis , Osteoarthritis, Knee/blood , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Biomarkers/analysis , Biomarkers/blood , Case-Control Studies , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Osteoarthritis, Knee/diagnosis , Osteoarthritis, Knee/metabolism , Peptide Fragments/analysis , Peptide Fragments/blood , Proteomics/methods , Reproducibility of Results , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Synovial Fluid/chemistry
14.
J Rheumatol ; 36(6): 1249-55, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19447933

ABSTRACT

OBJECTIVE: To determine which patients with ankylosing spondylitis (AS) have radiographic spinal damage and to investigate the relation between radiographic spinal changes and limitations in physical function. METHODS: A cross-sectional nationwide study in Belgium of patients with AS under the care of a rheumatologist. The treating physician completed a questionnaire including clinical disease manifestations and laboratory findings (HLA-B27 and C-reactive protein), and classified spinal radiographs into 3 categories: (1) no AS-related spinal abnormalities; (2) syndesmophytes; and (3) spinal ankylosis. Patients completed the Bath AS Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI). Ordinal regressions were performed to quantify the relationship between clinical manifestations and spinal radiographic changes. Generalized linear models were computed to quantify relationships among clinical manifestations, radiographic spinal changes, and functioning (BASFI). RESULTS: A total of 619 patients fulfilled modified New York criteria for definite AS and had evaluable radiographic data; 68% were male and disease duration was 17.5 (SD 12.2) years. Male sex, younger age at symptom onset, and hip involvement were associated with radiographic changes; but HLA-B27, peripheral arthritis, and extraarticular disease status (uveitis, psoriasis, and inflammatory bowel disease) were not. Older age, BASDAI, hip involvement, and spinal change contributed to BASFI; but sex, disease duration, peripheral arthritis, and extraarticular manifestations did not. CONCLUSION: Radiographic spinal changes in patients with AS are seen more often in men and those with hip involvement. BASFI status indicates the influence of radiographic changes and hip involvement, but does not reflect the presence of peripheral arthritis and does not differ between men and women.


Subject(s)
Health Status , Severity of Illness Index , Spine/diagnostic imaging , Spondylitis, Ankylosing/diagnostic imaging , Spondylitis, Ankylosing/physiopathology , Adolescent , Adult , Age of Onset , Ankylosis/diagnostic imaging , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Radiography , Spine/pathology , Spondylitis, Ankylosing/pathology , Surveys and Questionnaires , Young Adult
15.
Clin Chem ; 54(6): 1066-75, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18436720

ABSTRACT

BACKGROUND: SELDI-TOF mass spectrometry (MS) is a high-throughput proteomic approach with potential for identifying novel forms of serum biomarkers of arthritis. METHODS: We used SELDI-TOF MS to analyze serum samples from patients with various forms of inflammatory arthritis. Several protein profiles were collected on different Bio-Rad Laboratories ProteinChip arrays (CM10 and IMAC-Cu(2+)) and were evaluated statistically to select potential biomarkers. RESULTS: SELDI-TOF MS analyses identified several calgranulin proteins [S100A8 (calgranulin A), S100A9 (calgranulin B), S100A9*, and S100A12 (calgranulin C)], serum amyloid A (SAA), SAA des-Arg (SAA-R), and SAA des-Arg/des-Ser (SAA-RS) as biomarkers and confirmed the results with other techniques, such as western blotting, immunoprecipitation, and nano-LC-MS/MS. The S100 proteins were all able to significantly differentiate samples from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) from those of patients with inflammatory bowel diseases used as an inflammatory control (IC) group, whereas the SAA, SAA-R, and SAA-RS proteins were not, with the exception of AS. The 4 S100 proteins were coproduced in all of the pathologies and were significantly correlated with the plasma calprotectin concentration; however, these S100 proteins were correlated with the SAA peak intensities only in the RA and IC patient groups. In RA, these S100 proteins (except for S100A12) were significantly correlated with the serum concentrations of C-reactive protein, matrix metalloproteinase 3, and anti-cyclic citrullinated peptide and with the Disease Activity Score (DAS(28)). CONCLUSIONS: The SELDI-TOF MS technology is a powerful approach for analyzing the status of monomeric, truncated, or posttranslationally modified forms of arthritis biomarkers, such as the S100A8, S100A9, S100A12, and SAA proteins. The fact that the SELDI-TOF MS data were correlated with results obtained with the classic calprotectin ELISA test supports the reliability of this new proteomic technique.


Subject(s)
Arthritis/diagnosis , Leukocyte L1 Antigen Complex/blood , Adult , Aged , Arthritis/etiology , Arthritis, Rheumatoid/diagnosis , Biomarkers/blood , Calgranulin A/blood , Calgranulin B/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Psoriasis/complications , S100 Proteins/blood , S100A12 Protein , Serum Amyloid A Protein/analysis , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Spondylitis, Ankylosing/complications
17.
Ann Rheum Dis ; 66(8): 1072-7, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17261531

ABSTRACT

OBJECTIVES: This study aimed to describe the epidemiology of ankylosing spondylitis (AS) in rheumatology practice at the beginning of the anti-TNF (tumour necrosis factor) era, and to evaluate the initiation of anti-TNF therapy in a clinical setting where prescription is regulated by the authority's imposed reimbursement criteria. METHODS: Between February 2004 and February 2005, all Belgian rheumatologists in academic and non-academic outpatient settings were invited to register all AS patients who visited their practice. A random sample of these patients was further examined by an in-depth clinical profile. In a follow-up investigation, we recorded whether patients initiated anti-TNF therapy and compared this to their eligibility at baseline evaluation. RESULTS: 89 rheumatologists participated and registered 2141 patients; 1023 patients were clinically evaluated. These 847 fulfilled the New York modified criteria for definite AS and 176 for probable AS. The profile of AS in rheumatology practice is characterised by longstanding and active disease with a high frequency of extra-articular manifestations and metrological and functional impairment. At a median of 2 months after the clinical evaluation, anti-TNF therapy was initiated in 263 of 603 (44%) evaluable patients with definite AS and in 22 of 138 (16%) evaluable patients with probable AS (total 38%). More than 85% of the patients who started anti-TNF therapy had an increased Bath Ankylosing Spondylitis Disease Activity Index despite previous NSAID (non-steroidal anti-inflammatory drug) use. CONCLUSIONS: Of a representative cohort of 1023 Belgian AS patients seen in daily rheumatology practice, about 40% commenced anti-TNF therapy. Decision factors to start anti-TNF therapy may include disease activity and severity.


Subject(s)
Antirheumatic Agents/therapeutic use , Practice Patterns, Physicians' , Rheumatology , Spondylitis, Ankylosing/epidemiology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Antibodies, Monoclonal/economics , Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/economics , Belgium/epidemiology , Cohort Studies , Drug Costs , Etanercept , Female , Guideline Adherence , Humans , Immunoglobulin G/economics , Immunoglobulin G/therapeutic use , Infliximab , Logistic Models , Male , Middle Aged , Receptors, Tumor Necrosis Factor/therapeutic use , Registries , Severity of Illness Index , Spondylitis, Ankylosing/drug therapy
18.
Eur J Nucl Med Mol Imaging ; 33(3): 275-80, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16247604

ABSTRACT

PURPOSE: The aim of this study was to assess rheumatoid arthritis (RA) synovitis with positron emission tomography (PET) and( 18)F-fluorodeoxyglucose ((18)F-FDG) in comparison with dynamic magnetic resonance imaging (MRI) and ultrasonography (US). METHODS: Sixteen knees in 16 patients with active RA were assessed with PET, MRI and US at baseline and 4 weeks after initiation of anti-TNF-alpha treatment. All studies were performed within 4 days. Visual and semi-quantitative (standardised uptake value, SUV) analyses of the synovial uptake of FDG were performed. The dynamic enhancement rate and the static enhancement were measured after i.v. gadolinium injection and the synovial thickness was measured in the medial, lateral patellar and suprapatellar recesses by US. Serum levels of C-reactive protein (CRP) and metalloproteinase-3 (MMP-3) were also measured. RESULTS: PET was positive in 69% of knees while MRI and US were positive in 69% and 75%. Positivity on one imaging technique was strongly associated with positivity on the other two. PET-positive knees exhibited significantly higher SUVs, higher MRI parameters and greater synovial thickness compared with PET-negative knees, whereas serum CRP and MMP-3 levels were not significantly different. SUVs were significantly correlated with all MRI parameters, with synovial thickness and with serum CRP and MMP-3 levels at baseline. Changes in SUVs after 4 weeks were also correlated with changes in MRI parameters and in serum CRP and MMP-3 levels, but not with changes in synovial thickness. CONCLUSION: (18)F-FDG PET is a unique imaging technique for assessing the metabolic activity of synovitis. The PET findings are correlated with MRI and US assessments of the pannus in RA, as well as with the classical serum parameter of inflammation, CRP, and the synovium-derived parameter, serum MMP-3. Further studies are warranted to establish the place of metabolic imaging of synovitis in RA.


Subject(s)
Arthritis, Rheumatoid/diagnostic imaging , Fluorodeoxyglucose F18 , Knee Joint/diagnostic imaging , Matrix Metalloproteinase 3/blood , Synovitis/diagnostic imaging , Adult , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/pathology , Humans , Knee Joint/metabolism , Knee Joint/pathology , Magnetic Resonance Imaging , Middle Aged , Positron-Emission Tomography/methods , Radiopharmaceuticals , Reproducibility of Results , Sensitivity and Specificity , Statistics as Topic , Synovitis/blood , Synovitis/pathology , Ultrasonography
19.
Arthritis Rheum ; 52(12): 3801-12, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16320331

ABSTRACT

OBJECTIVE: To identify serum protein biomarkers specific for rheumatoid arthritis (RA), using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology. METHODS: A total of 103 serum samples from patients and healthy controls were analyzed. Thirty-four of the patients had a diagnosis of RA, based on the American College of Rheumatology criteria. The inflammation control group comprised 20 patients with psoriatic arthritis (PsA), 9 with asthma, and 10 with Crohn's disease. The noninflammation control group comprised 14 patients with knee osteoarthritis and 16 healthy control subjects. Serum protein profiles were obtained by SELDI-TOF-MS and compared in order to identify new biomarkers specific for RA. Data were analyzed by a machine learning algorithm called decision tree boosting, according to different preprocessing steps. RESULTS: The most discriminative mass/charge (m/z) values serving as potential biomarkers for RA were identified on arrays for both patients with RA versus controls and patients with RA versus patients with PsA. From among several candidates, the following peaks were highlighted: m/z values of 2,924 (RA versus controls on H4 arrays), 10,832 and 11,632 (RA versus controls on CM10 arrays), 4,824 (RA versus PsA on H4 arrays), and 4,666 (RA versus PsA on CM10 arrays). Positive results of proteomic analysis were associated with positive results of the anti-cyclic citrullinated peptide test. Our observations suggested that the 10,832 peak could represent myeloid-related protein 8. CONCLUSION: SELDI-TOF-MS technology allows rapid analysis of many serum samples, and use of decision tree boosting analysis as the main statistical method allowed us to propose a pattern of protein peaks specific for RA.


Subject(s)
Arthritis, Rheumatoid/blood , Biomarkers/blood , Protein Array Analysis/methods , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Adult , Aged , Arthritis, Psoriatic/blood , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/immunology , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/immunology , Autoantibodies/blood , Crohn Disease/blood , Crohn Disease/diagnosis , Crohn Disease/immunology , Decision Trees , Female , Humans , Male , Middle Aged , Peptides, Cyclic/immunology , Protein Array Analysis/standards , Reproducibility of Results , Sensitivity and Specificity , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/standards
20.
Arthritis Rheum ; 52(1): 84-93, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15641051

ABSTRACT

OBJECTIVE: Interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) activation of gp130 represents an alternative pathway for osteoclast development in inflammatory conditions. The goal of the present study was to investigate changes in sIL-6R levels in response to the inflammatory cytokines IL-1beta and tumor necrosis factor alpha (TNFalpha) and to determine the role of TNFalpha-converting enzyme (TACE) in this process. METHODS: Levels of sIL-6R in the culture media of MG63 and SAOS-2 osteoblast-like cell lines after exposure to various agents were determined by immunoassay. TACE protein levels were measured by Western immunoblotting. Cells were transfected with small interfering RNA (siRNA) or with an expression plasmid for IL-6R and TACE to determine the potential involvement of TACE in IL-6R shedding. RESULTS: IL-1beta and TNFalpha increased the levels of sIL-6R in the culture media of MG63 osteoblast-like cells. This effect was not influenced by cycloheximide or 5,6-dichlorobenzimidazole riboside but was markedly inhibited by the calcium chelator EGTA and by the TACE and matrix metalloproteinase inhibitor hydroxamate (Ru36156). IL-1beta and TNFalpha had no influence on the alternatively spliced form of IL-6R RNA. Levels of sIL-6R were reduced when MG63 cells were transiently transfected with TACE siRNA. Transfection of SAOS-2 cells with expression plasmids for IL-6R and TACE produced a dose-dependent increase in sIL-6R levels. CONCLUSION: IL-1beta- and TNFalpha-mediated induction of IL-6R shedding in osteoblast-like cells is at least partly dependent on TACE activation.


Subject(s)
Interleukin-1/pharmacology , Metalloendopeptidases/metabolism , Osteoblasts/metabolism , Receptors, Interleukin-6/metabolism , Tumor Necrosis Factor-alpha/pharmacology , ADAM Proteins , ADAM17 Protein , Cell Line, Tumor , Humans , Metalloendopeptidases/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/pharmacology , Receptors, Interleukin-6/biosynthesis , Receptors, Interleukin-6/chemistry , Receptors, Interleukin-6/genetics , Recombinant Proteins/pharmacology , Solubility , Transfection
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