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ID PMID Title PublicationDate abstract
25537932 Analysis of clinical factors related to the efficacy of shoulder arthroscopic synovectomy 2015 Apr Shoulder synovectomy is a well-known surgical treatment for rheumatoid arthritis. However, synovectomy alone is insufficient for improving range of motion clinically. We investigated the clinical factors related to the efficacy of shoulder synovectomy performed with capsular release in patients with rheumatoid arthritis. Fifty-four shoulders of 54 patients (12 males, 42 females; mean age 53.3 years) with rheumatoid arthritis were treated by synovectomy plus capsular release. The patients had a mean disease duration of 8.33 years, a mean follow-up period of 5.02 years, and 66.7% received biological treatment. The disease activity score 28 using C-reactive protein, range of motion of the shoulder, and Japanese Orthopaedic Association (JOA) score assessment were used to investigate clinical factors, analyzed by multiple regression analysis, associated with improved outcome. The average disease activity score 28 using C-reactive protein and JOA score improved significantly from 4.29 and 36.7 to 3.11 and 84.6, respectively, with the restoration of range of motion. Multiple regression analysis showed that disease duration and prednisolone were significantly associated with flexion degree and JOA score. Larsen grade and JOA score were not correlated significantly. There was no significant difference in the JOA score between the groups with or without biological medicinal treatment. Shoulder arthroscopic synovectomy performed with capsular release with or without biological treatment effectively improved function. Short disease duration and low prednisolone dose in rheumatoid arthritis were important for prediction of efficacy.
23739280 Association study of the platelet collagen receptor glycoprotein VI gene with rheumatoid a 2013 Sep OBJECTIVES: Beyond their role in haemostasis, platelets can actively contribute to immunity. The activation of the platelet collagen receptor glycoprotein VI (GPVI) promotes the release of small extracellular vesicles called microparticles. These microparticles are found in the joint bathing fluid of patients with rheumatoid arthritis (RA) and are thought to amplify inflammation. The gene coding for GPVI is localised on chromosome 19q13.4 and contains different single nucleotide polymorphisms (SNPs). Five non-synonymous SNPs define the major and minor haplotypes of GPVI. The minor haplotype is associated with higher risk of cardiovascular incidents. In this study, we examined whether this minor haplotype is also associated with RA. METHODS: Allelic discrimination of the SNPs reported to define these haplotypes encoding SKTQH and PEALN protein isoforms, ie rs1613662, rs1654416, rs2304167, rs1654413 and rs1671152, was performed in 399 RA patients and their two parents, all of Western European ethnicity. Statistical analysis relied on the transmission disequilibrium test by the use of the FBAT programme. Haplotypes were also estimated by the FBAT programme. RESULTS: We observed no statistically significant transmission disequilibrium for the SNPs tested. The major haplotype TAAC, which encodes the SKTQH isoform, was identified in 78% of our cohort individuals, and the CGGA haplotype which encodes the PEALN isoform was identified in 8% of our individuals. We observed no association of these haplotypes of the GPVI gene with RA. CONCLUSIONS: This demonstrates that the SNPs tested within the GPVI gene are not associated with RA susceptibility and/or severity, suggesting that platelet GPVI may contribute to arthritis independently of its gene polymorphism.
23729802 Serum pyridinoline levels and prediction of severity of joint destruction in rheumatoid ar 2013 Aug OBJECTIVE: Previous studies indicated that pyridinoline, a collagen crosslink in cartilage and bone, might be a good marker to predict joint destruction in patients with rheumatoid arthritis (RA), although large prospective studies are lacking. We evaluated the predictive value of serum pyridinoline levels for joint destruction, both at baseline for longterm prediction and during the disease course for near-term prediction. METHODS: Patients with early RA from the Leiden Early Arthritis Clinic were studied. Radiographs at baseline and yearly during 7 years of followup were scored according to the Sharp-van der Heijde Scoring (SHS) method. Pyridinoline serum levels at baseline and during followup were measured by ELISA. The association between baseline pyridinoline levels and difference in SHS over 7 years was tested, with a multivariate normal regression model. Second, the association between pyridinoline levels determined during the disease course and progression of SHS over the next year was tested with a multivariable linear regression analysis. RESULTS: Studying baseline pyridinoline serum levels in 437 patients revealed that the mean SHS over 7 years was 6% higher for every higher pyridinoline level (nmol/l) at baseline (p = 0.001). Subsequently, during followup (n = 184 patients) the progression in SHS in the upcoming year was 17% higher for every higher nmol/l pyridinoline level (p = 0.001). The area under the receiver-operation characteristic curve for rapid radiological progression was 0.59. CONCLUSION: Increased pyridinoline serum levels, both at baseline and during the disease course, are associated with more severe joint destruction during the coming year(s), although the predictive accuracy as a sole predictor was moderate.
23740824 Patient perspectives on achieving treat-to-target goals: a critical examination of patient 2013 Oct OBJECTIVE: Treat-to-target (T2T) recommendations suggest that rheumatoid arthritis (RA) patients should strive for remission or low disease activity (LDA). However, it is unclear whether patients experiencing a good response to biologic agents might experience further improvement in patient-reported outcomes (PROs) if they subsequently achieve a lower disease activity state, particularly the T2T goals of LDA or remission. METHODS: Using the Consortium of Rheumatology Researchers of North America database, we identified RA patients initiating biologic agents. We restricted the analysis to patients with improvement (Clinical Disease Activity Index [CDAI] improvement of ≥10 units) at 3-6 months (baseline visit; n = 1,368) with a followup visit approximately 9 months later (n = 984). Patients in CDAI remission or with a worsened disease activity category were excluded, leaving 562 eligible patients. PROs (global assessment, pain, and fatigue by 0-10 visual analog scales and disability by the modified Health Assessment Questionnaire [M-HAQ]) were examined at these 2 visits. Mean change in PROs compared achievement of a lower disease activity category versus staying in the same disease activity category, adjusting for potential confounders. RESULTS: Patients who achieved a lower disease activity category (40% of the eligible cohort, 86% of these achieving LDA or remission) had significantly better improvement in patient pain (-14.9; 95% confidence interval [95% CI] -18.4, -11.6), patient global (-17.5; 95% CI -20.8, -14.3), fatigue (-8.5; 95% CI -15.8, -1.3), and M-HAQ score (-0.13; 95% CI -0.18, -0.08) compared to patients who stayed in the same disease activity category. However, even for patients improving, fewer than half exceeded the minimum clinically important difference for each PRO. CONCLUSION: Achievement of a lower disease activity disease state, especially T2T goals, was associated with further improvement in PROs, albeit modest in magnitude.
25533052 Leptomeningeal rheumatoid nodules: diagnosis and failed therapeutics. 2015 Feb A 67-year-old woman presented with recurrent transient ischaemic attack-like episodes over a 2 year period. Nodular enhancing leptomeningeal changes were detected on MRI and were consistent with meningeal rheumatoid nodules on biopsy. The patient's nodular disease continued to progress and regress clinically and radiologically irrespective of disease modifying agents and peripheral and serological rheumatoid arthritis control. This patient's unique presentation and diagnostic work-up is discussed alongside the dilemma of therapeutic management of meningeal rheumatoid nodules.
25529148 TNF-α confers resistance to Fas-mediated apoptosis in rheumatoid arthritis through the in 2015 Feb 1 AIMS: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis that is characterized by hyperplastic synovial tissue containing activated synovial fibroblasts. Contradictory findings in the apoptosis of fibroblast-like synoviocytes (FLS) have been described elsewhere, showing that RA FLS have an enhanced susceptibility to Fas (also known as CD95)-mediated apoptosis in vitro in contrast to the observed lack of apoptosis in the RA synovium in vivo. However, the potential mechanisms responsible for this discrepancy remain under investigation. The soluble form of Fas (sFas) was found to inhibit Fas-induced apoptosis by binding to Fas ligand (FasL), thereby preventing the interaction between FasL and membrane-bound Fas. MAIN METHODS: We determined the levels of soluble FasL (sFasL) and sFas in patients with RA and the effects of proinflammatory mediators, including TNF-α, on the induction of apoptotic mediators in RA FLS. KEY FINDINGS: The levels of sFasL and sFas were significantly elevated in the synovial fluids of RA patients compared with control subjects. In addition, we found that the sFas is substantially induced in RA FLS by TNF-α, which were abundantly present in the synovial fluid of RA. SIGNIFICANCE: These findings suggest that TNF-α confers resistance to Fas-mediated apoptosis through sFas induction, which could explain the apparent resistance of RA synovial cells to apoptosis in vivo.
25173800 Cadherin-11 mRNA transcripts are frequently found in rheumatoid arthritis peripheral blood 2014 Nov Rheumatoid arthritis (RA) synovial fibroblasts hyperexpress the mesenchymal cadherin-11, which is involved also in tumor invasion/metastasis, whereas anti-cadherin-11 therapeutics prevent and reduce experimental arthritis. To test the hypothesis that cadherin-11 is aberrantly expressed in RA peripheral blood, 100 patients (15 studied serially) and 70 healthy controls were analyzed by real-time reverse transcription-PCR. Cadherin-11 mRNA transcripts were detected in 69.2% of moderately/severely active RA, versus 31.8% of remaining patients (p=0.001), versus 17.1% of controls (p<0.0001). Notably, cadherin-11 positivity correlated significantly and independently only with established (>1year) polyarthritis (>4 swollen tender joints), by multivariate logistic regression analysis including various possible clinical/laboratory factors. Rare cells of undefined nature, detected by flow cytometry following CD45(-) enrichment, strongly expressed surface cadherin-11 (estimated 10-50cells/ml of blood) in 5/6 patients with polyarticular established disease versus 1/6 patients with early RA. Studies on the potential pathogenic role of circulating cells expressing cadherin-11 in RA are warranted.
24684533 Aromatase and regulation of the estrogen-to-androgen ratio in synovial tissue inflammation 2014 May Sex hormones play an active role in inflammatory responses, with androgens being anti-inflammatory, whereas estrogens have both pro- and anti-inflammatory effects. In rheumatoid arthritis (RA) patients, low levels of androgens and high levels of estrone are found in the synovial fluid. Aromatase is the key enzyme for the conversion of androgens into estrogens. Proinflammatory cytokines stimulate aromatase activity so that the inflammatory milieu can induce conversion of androgens to estrogens. Moreover, testosterone inhibits aromatase activity. As local androgen levels are low in RA, this can contribute to high aromatase activity in the synovium. Importantly, aromatase-converted estrogens are converted into proproliferative and proinflammatory 16-hydroxylated estrogens. A hormone involved in aromatase activity is vitamin D, which downregulates aromatase in human RA macrophages. Collectively, evidence suggests a key role of aromatase in sex hormone balance during chronic inflammation and points to the importance of vitamin D as a possible new tool for aromatase modulation.
25466291 Shared signatures between rheumatoid arthritis, systemic lupus erythematosus and Sjögren' 2014 Dec 3 INTRODUCTION: Systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SjS) are inflammatory systemic autoimmune diseases (SADs) that share several clinical and pathological features. The shared biological mechanisms are not yet fully characterized. The objective of this study was to perform a meta-analysis using publicly available gene expression data about the three diseases to identify shared gene expression signatures and overlapping biological processes. METHODS: Previously reported gene expression datasets were selected and downloaded from the Gene Expression Omnibus database. Normalization and initial preprocessing were performed using the statistical programming language R and random effects model-based meta-analysis was carried out using INMEX software. Functional analysis of over- and underexpressed genes was done using the GeneCodis tool. RESULTS: The gene expression meta-analysis revealed a SAD signature composed of 371 differentially expressed genes in patients and healthy controls, 187 of which were underexpressed and 184 overexpressed. Many of these genes have previously been reported as significant biomarkers for individual diseases, but others provide new clues to the shared pathological state. Functional analysis showed that overexpressed genes were involved mainly in immune and inflammatory responses, mitotic cell cycles, cytokine-mediated signaling pathways, apoptotic processes, type I interferon-mediated signaling pathways and responses to viruses. Underexpressed genes were involved primarily in inhibition of protein synthesis. CONCLUSIONS: We define a common gene expression signature for SLE, RA and SjS. The analysis of this signature revealed relevant biological processes that may play important roles in the shared development of these pathologies.
23437156 Performance of the 2010 classification criteria for rheumatoid arthritis: a systematic lit 2013 OBJECTIVES: To evaluate the performance of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 classification criteria for rheumatoid arthritis (RA) with a systematic literature review and a meta-analysis. METHODS: PubMed, Embase, Cochrane Library and the abstracts of the ACR and EULAR meetings (2010-2012) were searched for original articles or abstracts with the following inclusion criteria: 1) recent onset arthritis, with at least one swollen joint and no alternative diagnosis; 2) the ACR/EULAR 2010 criteria as index test; 3) the prescription of methotrexate (MTX) or disease modifying antirheumatic drugs (DMARDs) at any time during follow-up as reference standard. Data were pooled using the bivariate model. Three meta-analyses were performed with MTX (primary analysis), DMARDs or their combination (secondary analyses) as reference standard. Heterogeneity was formally tested and explored performing an influence analysis. RESULTS: The search identified 1,277 references. Six full papers and 4 abstracts met the inclusion criteria. With MTX as reference standard, sensitivity (95% confidence interval, CI) was 0.80 (0.74,0.85), specificity 0.61 (0.56,0.67), positive likelihood ratio (LR) 2.11 (1.92,2.32), negative LR 0.31 (0.25,0.38) and the diagnostic odds ratio (DOR) was 6.74 (5.49,8.28). Using DMARDs as reference standard, sensitivity was 0.73 (0.64,0.80), specificity was 0.74 (0.68,0.79), LR+2.85 (2.53,3.22), LR- 0.35 (0.27,0.45) and DOR 8.03 (6.4,10.09). Using the combination of MTX and DMARDs as reference standard, intermediate results were obtained. The influence analysis detected one potentially influential study. However, its exclusion from the meta-analysis did not have a clinically relevant impact on the results. CONCLUSIONS: The new classification criteria have good sensitivity, lower specificity and an overall moderate diagnostic accuracy. These results confirm that the criteria have classificative and not diagnostic function.
25365090 RADAI-5 to monitor rheumatoid arthritis. 2014 Sep Providing the physician with sufficient information about the disease course can be regarded as the most important requirement for any disease assessment tool besides easy applicability and time-sparing documentation. Applying the RADAI-5 in daily routine provides the patient's view at any time completing the questionnaire. In a first study, the RADAI-5 resulted to be highly significantly correlated to the RADAI, and all composite indexes. Changes of the RADAI-5, the DAS28-ESR, and the CDAI were significantly correlated, indicating the instrument's sensitivity to change. A second study including 392 RA patients led to the establishment of thresholds for disease activity categories according to the RADAI-5, as follows: 0.0 up to 1.4 for a remission-like state, 1.6 up to 3.0 for mild disease activity, 3.2 up to 5.4 for moderate and from 5.6 up to 10.0 for high disease activity. In a third study, remission according to the RADAI-5 appeared to be highly specific for the ACR/EULAR criteria for remission The RADAI-5 questionnaire constitutes an easily applicable tool for routine RA monitoring, providing physicians with reliable information about the disease course and sensitivity enough to sound the alarm should complications occur.
23433179 CD154: the atherosclerotic risk factor in rheumatoid arthritis? 2013 Feb 22 Atherosclerosis, now regarded as a chronic inflammatory disease of the arterial wall, and its clinical manifestations have increasingly been associated with rheumatoid arthritis (RA), supporting the notion that autoimmune diseases and vascular disorders share common etiological features. Indeed, evidence pertaining to this matter indicates that inflammation and its multiple components are the driving force behind the pathogenesis of these disorders. Interestingly, CD154 and its receptors have emerged as major players in the development of RA and atherosclerosis, which raises the possibility that this axis may represent an important biological link between both complications. Indeed, CD154 signaling elicits critical inflammatory responses that are common to the pathogenesis of both diseases. Here, we provide an overview of the traditional and disease-related interrelations between RA and vascular abnormalities, while focusing on CD154 as a potential mediator in the development of atherosclerotic events in RA patients.
25179669 An updated meta-analysis of the signal transducer and activator of transcription 4 (STAT4) 2014 OBJECTIVES: Signal transducer and activator of transcription 4 (STAT4) transmits signals induced by the cytokines interleukin (IL)-12, IL-23, and interferon (IFN)-γ, which play an important role in the development of rheumatoid arthritis (RA). Studies have shown conflicting results concerning the association between the rs7574865 G/T polymorphism in the STAT4 gene and RA in an Asian population. We have performed a meta-analysis to examine this relationship. METHOD: We searched PubMed and WanFang databases for all papers published up to 5 October 2013. Eight case-control studies with 6029 cases and 4685 controls were retrieved based on the search criteria for RA susceptibility related to the STAT4 rs7574865 G/T polymorphism. Risk ratios (RRs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed using Begg's test. RESULTS: A significant association was found between the STAT4 rs7574865 G/T polymorphism and RA risk (e.g. GG+GT vs. TT: RR 0.96, 95% CI 0.95-0.97; GG+TT vs. GT: RR 0.94, 95% CI 0.91-0.97). Subgroup analysis of rheumatoid factor (RF) status revealed a protective relationship between the STAT4 rs7574865 G/T polymorphism and RF(+)/RF(-) RA risk. A similar relationship was detected in the anti-cyclic citrullinated peptide (CCP) status subgroup. No clear evidence of publication bias was detected in the overall analysis. CONCLUSIONS: Our study indicates that the STAT4 rs7574865 G/T polymorphism was significantly associated with a decreased RA risk in an Asian population.
22952388 Improved early identification of arthritis: evaluating the efficacy of Early Arthritis Rec 2013 Aug OBJECTIVE: Only 31% of Dutch rheumatoid arthritis (RA)-patients visit a rheumatologist within 12 weeks after symptom onset; this is mainly due to delay at the level of the general practitioner (GP). In order to reduce delay of GPs in identifying early arthritis, we initiated an Early Arthritis Recognition Clinic (EARC). METHODS: EARCs were initiated at the Leiden and Groningen University Medical Centers. At this EARC, patients filled in a questionnaire about their symptoms, followed by a short visit with only a full joint examination by an experienced rheumatologist. If arthritis was present the patient got an appointment the same week at the regular outpatient clinic. The main outcome parameter was the GP-delay; the secondary outcome parameter was the total delay. In both centres, patients included in early arthritis clinics that had arrived via regular referrals served as control group. RESULTS: Four hundred patients visited the Leiden EARC and 212 patients the Groningen EARC. Arthritis was detected in 42% and 49% respectively. The median GP-delay for these arthritis patients was 2.0 (0.4-7.3) and 2.0 (0.4-10.0) weeks and the median total delay 8.6 (3.6-22.3) and 10.6 (3.1-30.8) weeks respectively. At these two clinics 59% and 51% of all arthritis patients and 65% and 53% of the patients that were subsequently diagnosed with undifferentiated arthritis or RA were seen within 12 weeks after symptom onset. In the Leiden and Groningen control groups that arrived via regular referrals, only 32% and 38% were seen within 12 weeks time. CONCLUSIONS: The EARC increased the early identification of arthritis and RA.
24847752 A case of methimazole-induced chronic arthritis masquerading as seronegative rheumatoid ar 2014 Jun We report a 40-year-old woman with onset of oligoarthritis shortly after initiating treatment with methimazole for Graves disease. Over the course of 7 years, her arthritis became progressively severe, leading to a diagnosis of seronegative rheumatoid arthritis. Treatment with disease-modifying antirheumatic agents and surgical intervention was contemplated. Ultrasound and magnetic resonance imaging revealed exuberant synovitis, involving right elbow and knees. Upon withdrawal of methimazole, prompt resolution of all signs and symptoms of arthritis was observed within several weeks. Following a MEDLINE search of available literature concerning antithyroid drug-induced arthritis, it is evident that this case represents the lengthiest duration of inflammatory arthropathy ever described in a patient that nonetheless was rapidly reversible with discontinuation of methimazole.
24893961 A hyaluronic acid-methotrexate conjugate for targeted therapy of rheumatoid arthritis. 2014 Jul 21 In an effort to improve the therapeutic efficacy of methotrexate (MTX), we prepared the hyaluronic acid-MTX conjugate for targeted therapy of rheumatoid arthritis (RA). Owing to the pH-sensitive nature of the conjugate, MTX was rapidly released under the mildly acidic conditions, similar to the environment of inflamed synovial tissue in RA.
25195628 A case with rheumatod arthritis and atraumatic odontoid fracture: disappearence of bony la 2018 Nov We aim to draw attention to occult, atraumatic fractures of the odontoid process in patients with rheumatoid arthritis (RA) and to underline difficulties encountered during clinical and radiological diagnosis. A forty-seven years old man with RA for 4 years had occipital pain for 1 year without any history of trauma. Later, he developed weakness in the upper extremities, but he did not realize weakness in the lower extremities due to deformities. Contrast magnetic resonance imaging revealed a linear fracture of odontiod process and myelopathy. Cervical computed tomography scan revealed an old fracture border with separated and almost disappeared remnant of the tip of the odontoid without free particles in the cord. It was impossible to evaluate atlantoaxial and vertical subluxations with craniometric measurements due to destruction of the tip of odontoid. Following occipitocervical fusion and decompression and a rehabilitation program, his muscle strength improved; however, functional myelopathy stage did not change. Atraumatic fractures of the odontoid process may be more common than reported and may cause compression of the spinal cord or brain stem. Surgery is the treatment of choice but functional recovery is limited once neuronal damage has occurred. Erosion of the critical landmarks makes it difficult to diagnose and follow up atlantoaxial subluxation and/or vertical subluxation, therefore clinicians should consider radiographical follow-ups during the course of the disease.
25270553 Dynamic contrast-enhanced magnetic resonance imaging of metacarpophalangeal joints reflect 2014 Oct 1 INTRODUCTION: Synovial inflammation and joint destruction in rheumatoid arthritis (RA) may progress despite clinical remission. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is increasingly used to detect synovial inflammation in RA. Although small joints such as metacarpophalangeal (MCP) joints are mainly affected by RA, MRI findings have never been directly compared to histological synovitis in MCP synovial tissue. The objective of the current study was therefore to analyse if DCE-MRI relates to histological signs of synovitis small RA joints. METHODS: In 9 RA patients, DCE-MRI (3 Tesla, dynamic 2D T1 weighted turbo-flash sequence) of the hand was performed prior to arthroscopically-guided synovial biopsies from the second MCP of the imaged hand. Maximum enhancement (ME), rate of early enhancement, and maximum rate of enhancement were assessed in the MCP. Synovial biopsies were stained for determination of sublining CD68 and the Synovitis Score. Correlations between MRI and histological data were calculated according to Spearman. RESULTS: ME of the MCP significantly correlated to sublining CD68 staining (r = 0.750, P = 0.02), the Synovitis Score (r = 0.743, P = 0.02), and the subscores for lining layer hypertrophy (r = 0.789, P = 0.01) and cellular density (r = 0.842; P = 0.004). CONCLUSIONS: Perfusion imaging of synovial tissue in RA finger joints employing DCE-MRI reflects histological synovial inflammation. According to our study, ME is the most closely associated parameter amongst the measures considered.
24838364 Emotions related to participation restrictions as experienced by patients with early rheum 2014 Psychological distress is a well-known complication in rheumatoid arthritis (RA), but knowledge regarding emotions and their relationship to participation restrictions is scarce. The objective of the study was to explore emotions related to participation restrictions by patients with early RA. In this study, 48 patients with early RA, aged 20-63 years, were interviewed about participation restrictions using the critical incident technique. Information from transcribed interviews was converted into dilemmas and linked to International Classification of Functioning, Disability, and Health (ICF) participation codes. The emotions described were condensed and categorized. Hopelessness and sadness were described when trying to perform daily activities such as getting up in the mornings and getting dressed, or not being able to perform duties at work. Sadness was experienced in relation to not being able to continue leisure activities or care for children. Examples of fear descriptions were found in relation to deteriorating health and fumble fear, which made the individual withdraw from activities as a result of mistrusting the body. Anger and irritation were described in relation to domestic and employed work but also in social relations where the individual felt unable to continue valued activities. Shame or embarrassment was described when participation restrictions became visible in public. Feelings of grief, aggressiveness, fear, and shame are emotions closely related to participation restrictions in everyday life in early RA. Emotions related to disability need to be addressed both in clinical settings in order to optimize rehabilitative multi-professional interventions and in research to achieve further knowledge.
24892812 Anti-citrullinated peptide antibodies and rheumatoid factor isotypes in the diagnosis of r 2014 Sep 25 ACPA (anti-citrullinated protein antibody) tests are today systematically added to clinical and radiological investigations when diagnosing rheumatoid arthritis (RA), and the inclusion of ACPA positivity in the new 2010 RA criteria underlines their importance. The aim of this study was to determine the sensitivity and specificity of different ACPA assays and IgA, IgG and IgM isotypes of rheumatoid factor (RF) in a cohort of patients with early RA in order to assess the value of combining the tests. The serum samples were obtained from 46 RA patients, 80 patients with systemic rheumatic disease, and 20 blood donors. ACPAs were measured using five different commercial kits. The receiver operating characteristic (ROC) curves of the anti-ACPA tests had area under the curve (AUC) values of 0.60-0.83. The diagnostic accuracy of the Bio-Rad multiplex flow immunoassay, a new technology for ACPA testing, was very similar to that of the other widely used commercial immunoassays. The EliA CCP-Phadia test was the most specific, and had the best positive likelihood ratio and positive predictive values, whereas the anti-CCP Inova 3.1 test was the most sensitive, and had the best negative likelihood ratio and negative predictive values. The best combination to use for early RA screening was an ACPA test together with IgM and IgA RF.