Non-erosive Rheumatoid Arthritis Research Articles

Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid Arthritis.

Evidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion. Thirty-nine premenopausal RA patients were consecutively enrolled and divided into two groups based on the presence of bone erosions on hand joints. Classical monocytes were isolated from peripheral blood through negative selection, and RNA-seq was performed using a poly-A enrichment kit and Illumina® platform. Classical monocytes transcriptome from healthy age-matched women were also included to identify differentially expressed genes (DEGs). Therefore, gene sets analysis was performed to identify the enriched biological pathways. RNA-seq analysis resulted in the identification of 1,140 DEGs of which 89 were up-regulated and 1,051 down-regulated in RA patients with bone erosion compared to those without bone erosions. Among up-regulated genes, there was a highlighted expression of IL18RAP and KLF14 related to the production of pro-inflammatory cytokines, innate and adaptive immune response. Genes related to collagen metabolism (LARP6) and bone formation process (PAPPA) were down-regulated in RA patients with erosions. Enriched pathways in patients with erosions were associated with greater activation of immune activation, and inflammation. Interestingly, pathways associated with osteoblast differentiation and regulation of Wnt signaling were less activated in RA patients with erosions. These findings suggest that alterations in expression of monocyte genes related to the inflammatory process and impairment of bone formation might have an important role in the pathophysiology of bone erosions in RA patients.

OA19 A complex case of bilateral pneumothoraces due to probable certolizumab driven rheumatoid lung nodules

OA19 A complex case of bilateral pneumothoraces due to probable certolizumab driven rheumatoid lung nodules

Osteoclast microRNA Profiling in Rheumatoid Arthritis to Capture the Erosive Factor.

In rheumatoid arthritis (RA), only a subset of patients develop irreversible bone destruction. Our aim was to identify a microRNA (miR)-based osteoclast-related signature predictive of erosiveness in RA. Seventy-six adults with erosive (E) or nonerosive (NE) seropositive RA and 43 sex- and age-matched healthy controls were recruited. Twenty-five miRs from peripheral blood mononuclear cell (PBMC)-derived osteoclasts selected from RNA-Seq (discovery cohort) were assessed by qPCR (replication cohort), as were 33 target genes (direct targets or associated with regulated pathways). The top five miRs found differentially expressed in RA osteoclasts were either decreased (hsa-miR-34a-3p, 365b-3p, 374a-3p, and 511-3p [E versus NE]) or increased (hsa-miR-193b-3p [E versus controls]). In vitro, inhibition of miR-34a-3p had an impact on osteoclast bone resorption. An integrative network analysis of miRs and their targets highlighted correlations between mRNA and miR expression, both negative (CD38, CD80, SIRT1) and positive (MITF), and differential gene expression between NE versus E (GXYLT1, MITF) or versus controls (CD38, KLF4). Machine-learning models were used to evaluate the value of miRs and target genes, in combination with clinical data, to predict erosion. One model, including a set of miRs (predominantly 365b-3p) combined with rheumatoid factor titer, provided 70% accuracy (area under the curve [AUC] 0.66). Adding genes directly targeted or belonging to related pathways improved the predictive power of the model for the erosive phenotype (78% accuracy, AUC 0.85). This proof-of-concept study indicates that identification of RA subjects at risk of erosions may be improved by studying miR expression in PBMC-derived osteoclasts, suggesting novel approaches toward personalized treatment. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Matrix Metalloproteinase-9 Level in Synovial Fluid-Association with Joint Destruction in Early Rheumatoid Arthritis.

Background and objective: Matrix metalloproteinases (MMPs) are the key enzymes in the pathogenesis of cartilage and joint damage and potentially a new biomarker of the early erosive form of rheumatoid arthritis (RA). Firstly, the study aimed to compare the level of MMP-9 in plasma (PL) and synovial fluid (SF) of patients with RA and osteoarthritis (OA). Secondly, the goal was to examine the association of MMP-9 level in PL and SF with early erosive changes in RA, and finally, to determine the association of MMP-9 level with serological parameters of the disease (rheumatoid factor-RF and anti-citrulline protein antibodies-ACPA). Materials and Methods: A total of 156 subjects were involved in this study (84 patients with RA and 72 patients with OA, who were involved as a control group). MMP-9 level was measured in PL and SF of all subjects by the sandwich enzyme-linked immunosorbent assay (ELISA) method. Standard radiographs of the hands and feet were used to detect joint damage and classification into erosive or non-erosive RA. The Larsen score (LS) was used for the quantitative assessment of joint damage, and its annual change (∆ LS) was used to assess the radiographic progression of the disease. Results: MMP-9 level in PL and SF was significantly higher in RA compared to controls (PL: 19.26 ± 7.54 vs. 14.57 ± 3.11 ng/mL, p< 0.01; SF: 16.17 ± 12.25 vs. 0.75 ± 0.53 ng/mL, p < 0.001) as well as in SF of patients with erosive compared to non-erosive RA (18.43 ± 12.87 vs. 9.36 ± 7.72; p < 0.05). Faster radiographic progression was recorded in erosive compared to non-erosive early RA (11.14 ± 4.75 vs. 6.13 ± 2.72; p < 0.01). MMP-9 level in SF, but not in PL, significantly correlates with the radiographic progression in both erosive and non-erosive RA (ρ = 0.38 and ρ = 0.27). We did not find a significant association between RF and MMP-9 level in early RA, but the ACPA level significantly correlates with MMP-9 level in SF (r = 0.48). Conclusion: The level of MMP-9 in plasma and synovial fluid of patients with RA is significantly higher compared to patients with osteoarthritis. The level of MMP-9 in synovial fluid is significantly higher in erosive than non-erosive early RA. It is significantly associated with the radiographic progression of the disease and the level of anti-citrulline protein antibodies.

Erosion-free rheumatoid arthritis: clinical and conceptional implications—a BARFOT study

BackgroundBone erosions may appear early or later during rheumatoid arthritis (RA), causing joint damage and functional impairment. However, in some patients erosions do not occur, even after several years of disease. This study evaluates the prevalence, clinical relevance and possible predictors of erosion-free RA.MethodsSix hundred and eight patients from an early RA cohort (BARFOT) having radiographs of hands and feet at inclusion and after 1, 2, 5 and 8 years were studied. Clinical and functional assessments were performed on all these time-points.ResultsIn all, 144 patients (24%) did not develop erosions up to 8 years follow-up (Never erosive group), while 464 patients (76%) had erosions on one or more assessments (Ever erosive group). At diagnosis, the patients in the Never erosive group were significantly younger, satisfied fewer ACR criteria, and were less frequently RF- and/or anti-CCP- positive compared with those in the Ever erosive group. The Never erosive patients had consistently more tender joints, lower erythrocyte sedimentation rate (ESR) and, from two years and onwards, fewer swollen joints. Absence of rheumatoid factor (RF) and/or anti-CCP were strong independent predictors for erosion-free disease. The erosion-free patients were less frequently treated with DMARDs and/or prednisolone.ConclusionsOne-quarter of the patients was erosion-free during eight years in this early RA cohort. Erosion-free patients had a less severe disease course as to disease activity and were more often seronegative compared with those with erosive disease. The results suggest that non-erosive RA represents a milder form of RA.

MicroRNA-17-5p Reduces Inflammation and Bone Erosions in Mice With Collagen-Induced Arthritis and Directly Targets the JAK/STAT Pathway in Rheumatoid Arthritis Fibroblast-like Synoviocytes.

We undertook this study to examine microRNA (miRNA) expression across rheumatoid arthritis (RA) phenotypes, along with the effects and mechanisms of action of miRNA-17-5p (miR-17). A miRNA array was performed in synovial tissue biopsied from patients with naive erosive RA (n = 3) and patients with nonerosive RA (n = 3). MicroRNA-17 lipoplex was delivered intraarticularly in the murine collagen-induced arthritis model. Clinical, histologic, and structural effects were studied over the course of arthritis. In-depth studies of the mechanisms of action of miR-17 were performed in primary RA fibroblast-like synoviocytes (FLS) isolated from synovial tissue. Fifty-five miRNAs including miR-17 were reduced in erosive RA. The miR-17 transfection into arthritic paws reduced the clinical inflammation score between day 2 and day 7 (2.8 versus 1.9; P = 0.03). Synovial B cell, T cell, macrophage, and polynuclear neutrophil infiltration was significantly reduced. Structural damage was also decreased, as shown by a reduction in the number of osteoclasts detected using tartrate-resistant acid phosphatase staining (osteoclast surface/bone surface 32% versus 18%; P = 0.005) and erosion score by computed tomography analysis (2.9 versus 1.7; P = 0.023). Proinflammatory cytokines from the interleukin-6 (IL-6) family and IL-1β expression were also significantly reduced, but tumor necrosis factor was not. MicroRNA-17 directly targeted the 3'-untranslated regions of STAT3 and JAK1. STAT3 and JAK1 messenger RNA (mRNA) and protein expression were reduced in RA FLS following miR-17 transfection. STAT3 and JAK1 mRNA and activation of STAT3, as assessed by immunohistochemistry, were also reduced in injected paws (% stained area 93% versus 62%; P = 0.035). We demonstrate an antiinflammatory and antierosive role of miR-17 in vivo. This effect involves the suppression of the IL-6 family autocrine-amplifying loop through the direct targeting of JAK1 and STAT3.

Distribution of erosions in hands and feet at the time for the diagnosis of RA and during 8-year follow-up

BackgroundJoint destruction in rheumatoid arthritis (RA) is usually evaluated by radiographs of both hands and feet, while the inflammatory status mostly is evaluated by DAS28 which, however, does not include the feet.ObjectivesTo investigate the distribution of erosions in hands and feet in early RA over 8 years and its potential clinical implications. Furthermore, the group of patients never showing erosions has been addressed.MethodsThis study comprises 1041 patients from the BARFOT study of patients with early RA. Radiographs of hands and feet were performed at baseline, 1, 2, 5, and 8 years and evaluated by the Sharp van der Heijde scoring (SHS) method (32 joints in the hands and 12 in the feet). Disease activity was measured by DAS28, SR, CRP, and function with HAQ.ResultsIn the feet, there were significantly more eroded joints in percent of examined joints than in the hands at all time points. Patients with erosions only in the feet were younger, more often seropositive and smokers. They had significantly lower baseline DAS28, than the patients with erosions only in the hands. The patients without erosions over time were, at diagnosis, significantly younger and less frequently seropositive compared with patients having erosions.ConclusionsThis study highlights the importance of evaluating the feet in patients with RA, both with clinical examinations and with imaging and lends support to the notion that seropositivity and smoking are risk factors for erosive disease. Further studies of patients with nonerosive disease are needed.Key Points:• Foot problems are common in RA• This study emphasizes the limitations of DAS28 and Sharp van der Heijde score as regards evaluating disease activity and radiographic damage• This study highlights the importance of evaluating the feet in patients with RA with clinical examinations and imaging• This study also points out the need of further studies of patients with non-erosive RA.

A RARE COMPLICATION OF TUMOR NECROSIS FACTOR INHIBITORS

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Tumor necrosis factor (TNF)-inhibitors are one of the first line agents prescribed for management of rheumatoid arthritis (RA). Hemorrhagic pericardial effusion is a rare side effect of TNF inhibitors1,2, and if left untreated, may cause life threatening complications such as pericardial tamponade or cardiac arrest. CASE PRESENTATION: A thirty-four-year-old morbidly obese female with past medical history of Diabetes and RA presented to the emergency department after a syncopal episode with complains of shortness of breath and anxiety. An emergent Computed tomography scan was done which showed a large pericardial effusion. (Figure 1). As the patient was being transported to intensive care, she developed hypotension and hypoxia leading to cardiac arrest. Cardiopulmonary resuscitation was started. A bedside echocardiogram showed a large circumferential pericardial effusion with tamponade physiology (Figure 2). Return of spontaneous circulation was achieved after six rounds of compressions but the patient remained in obstructive shock requiring multiple vasopressors. An emergent bedside pericardiocentesis was performed and 60cc fluid was drained. She was then taken to the catheterization lab with further drainage of 550cc of hemorrhagic fluid. Post drainage her hypotension resolved and she was weaned off of all vasopressors. Pericardial studies showed an elevated red blood cell with a normal white blood cell count, negative culture and cytology. Autoimmune workup showed elevated histone antibodies. Of note, the patient had a history of seropositive, non-erosive RA which was managed with prednisone and adalimumab. Due to decreased response to adalimumab, patient was switched to etanercept and received her first dose one month prior to presentation which was discontinued after patient developed skin peeling. DISCUSSION: The exact mechanism of TNF-inhibitors causing pericardial tamponade is currently unknown. However, some have proposed a paradoxical flare up of the underlying autoimmune condition, immune-mediated or drug induced reactions as the cause. Even though RA can occasionally cause pericardial effusions, they are not typically hemorrhagic in nature. The significant medication history in our patient along with anti-histone antibodies made drug induced pericardial effusion the likely cause. More research needs to be done to ascertain the pathophysiology of effusions due to TNF-Inhibitors, as with increasing utility of TNF-inhibitors, they may be more common than currently documented. CONCLUSIONS: With increased use of TNF-inhibitors in autoimmune conditions, clinicians should be well aware of their side effect profile as a delayed diagnosis may lead to life threatening complications as was evident in our case. Reference #1: Lather HD, Kahlenberg JM. Hemorrhagic Pericardial Effusion with Tamponade: A Rare Adverse Effect of Infliximab-Case Report and Literature Review. Case reports in rheumatology. 2016;2016:2576496 Reference #2: Soh MC, Hart HH, Corkill M. Pericardial effusions with tamponade and visceral constriction in patients with rheumatoid arthritis on tumour necrosis factor (TNF)-inhibitor therapy. International journal of rheumatic diseases. 2009;12(1):74-77. DISCLOSURES: No relevant relationships by Kourtney Erickson, source=Admin input No relevant relationships by Sara Godil, source=Web Response No relevant relationships by Kareem Godil, source=Web Response No relevant relationships by Emilee Kurtz, source=Web Response

FLARE OF RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE SECONDARY TO LUNG BIOPSY

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) often presents with dyspnea and a nonproductive cough. The progression and prognosis of the disease are usually determined by the ILD subtype. The most common subtype is usual interstitial pneumonia (UIP) followed by non-specific interstitial pneumonia (NSIP)[1]. For most, the disease remains sub-clinical without progression. Flares can occur, being precipitated by insult to the lungs including infection and even lung biopsy[2]. CASE PRESENTATION: A 44-year-old female with a history of non-erosive rheumatoid arthritis on methotrexate, IV drug abuse, and slowly progressive ILD presented to the hospital due to hypoxemia and worsening cough. Computed tomography (CT) of the chest demonstrated interlobular septal thickening, subpleural peripheral honeycombing and ground-glass opacities with a bibasilar and posterior predominance. Methotrexate was discontinued and the patient was started on broad spectrum antibiotics with initiation of an infectious workup. Due to her unclear etiology of lung disease and failure to improve on antibiotics, a video assisted right upper lung biopsy on day six of hospitalization was performed. The pathology showed fibrosis with honeycombing and dilatation of bronchi consistent with UIP. The patient was then started on pulse dose steroids and rituximab as her hypoxia worsened. Eleven days after biopsy the patient was emergently intubated and ultimately placed on veno-venous extracorporeal membrane oxygenation (VV-ECMO) for refractory hypoxemia. Her course was complicated by streptococcal bacteremia with septic shock, Pseudomonas ventilator associated pneumonia, superior vena cava thrombus, and severe oropharyngeal bleeding. Unfortunately, the patient was not a candidate for lung transplant due to her severity of illness and multiple infections. She was ultimately taken off of life support on day 68 of hospitalization. DISCUSSION: Acute respiratory failure of unclear etiology can be difficult to treat as management can vary drastically. The differential diagnosis in this case includes methotrexate toxicity, infection, and RA-ILD. Ultimately the patient was diagnosed with a flare of her ILD with surgical lung biopsy possibly further exacerbating the flare. Biopsy may have been avoided with her CT findings being consistent with UIP pattern. One could argue that pathology would likely show similar findings and not be contributory to changing the course of treatment. Regardless of the cause, RA-ILD flares can be difficult to manage as treatment with steroids may not be enough and rituximab can take up to 4-6 weeks before seeing clinical improvement, if at all. CONCLUSIONS: RA-ILD can atypically progress at a rapid rate. When considering open lung biopsy, it is judicious to weigh the risks versus the benefits involved. For patients with already progressive ILD, flares must be considered as one of those risks. Reference #1: Solomon JJ, Chung JH, Cosgrove GP, et al. Predictors of mortality in rheumatoid arthritis-associated interstitial lung diseases. Eur Respir J. 2016;47(2):588-96. Reference #2: Bando M, Ohno S, Hosono T, et al. Risk of acute exacerbation after video-assisted thorascopic lung biopsy for interstitial lung disease. J Bronchology Interv Pulmonol 2009;16(4):229-35. DISCLOSURES: No relevant relationships by Jessica Boehmler, source=Web Response No relevant relationships by Nathan Brewster, source=Web Response No relevant relationships by Kareem Godil, source=Web Response No relevant relationships by Breanna Goldner, source=Web Response No relevant relationships by Ethan Stern, source=Web Response

Characteristics and treatment of rheumatologic adverse events associated with immune checkpoint inhibitors: A multicentric prospective cohort study.

e14133 Background: To characterise the specific rheumatologic immune-related adverse events (irAEs) in patients with cancer treated by immune checkpoint inhibitors (ICI), and to propose a treatment flowchart of irAEs. Methods: A multicentric prospective study was performed to characterise the irAEs. Results: From December 2016 to December 2018, 39 patients were referred to the Department of Rheumatology. There were 22 men and 17 women. The middle age was 64,72 years old. The average time to continue ICI treatment after the onset of the irAEs was 3 months. 24 patients were followed for a melanoma, 10 for non-small cell lung cancers and five patients for various other neoplasia (glioblastoma, urothelial carcinoma, Merkel cell carcinoma, esophageal carcinoma, renal cell carcinoma). 43% had inflammatory pain (n = 17), whose 17% had arthritis (n = 7). The diagnosis was polymyalgia rheumatica for 10 patients, eosinophilic fasciitis for one patient, erosive Rheumatoid arthritis for one patient, non-erosive Rheumatoid arthritis for one patient. The other patients (57 %) had mechanical rheumatological involvement. Treatment of irAEs was glucocorticoids for 7 patients with a satisfying response, methotrexate for 1 patient, and sulfasalazine for one patient. The non-inflammatory pain was treated by antalgics and physiotherapy. The ICI was stopped (due to irAEs) for only one patient. Conclusions: In the light of these findings, a logigram of management is proposed and is being validated on a larger prospective cohort. irAEs is a good example of collaboration between oncologist and rheumatologist to improve the patients’ quality of life.

Diagnostic accuracy of simplified ultrasound hand examination protocols for detection of inflammation and disease burden in patients with rheumatoid arthritis.

There is no consensus regarding the minimum number of joints that should be included in an ultrasound (US) scoring system to reliably assess for disease activity in rheumatoid arthritis (RA). To assess whether simplified US protocols for hand examination are as informative as the examination of 22 joints in patients with RA, and to correlate the US parameters with disease activity (DAS-28). This is a cross-sectional study of 224 RA patients stratified based on their DAS-28 scores and assessed using eight preselected US examination protocols, including 22, 18, 16, 14, ten, eight, and two different combinations of four joints, respectively. We found a significant difference between US hand scores regarding their ability to detect active inflammation and erosions. DAS-28 scores correlated very well with the power Doppler (PD) scores generated by all eight US examination protocols (r = 0.89-1, P < 0.05), irrespective of patients' disease activity. Simplified US scores missed information on presence of PD in 20.6-40.2% patients ( P < 0.05) and misdiagnosed non-erosive hand RA in 12-38.4% patients ( P < 0.05), depending on the number of joints excluded from US hand examination. Preselected simplified US scores are less reliable in appreciating the disease burden when compared with an extended protocol for 22 joint US examination, raising clinicians' awareness regarding the need to comprehensively assess multiple hand joints to reliably rule out subclinical inflammation.

Association of tumor necrosis factor-α (G-308A) genetic variant with matrix metalloproteinase-9 activity and joint destruction in early rheumatoid arthritis.

Matrix metalloproteinases (MMPs) are the key enzymes responsible for the joint destruction. Their activity is regulated by the level of proinflammatory cytokines. The aim of this study was to examine the impact of TNF-α G-308A polymorphism on MMP-9 levels in blood plasma (BP) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and their role in progression of joint destruction. One hundred thirty-four subjects were enrolled in this study. TNF-α G-308A polymorphism was determined using PCR-RFLP method. ELISA assay was used for the detection of MMP-9 activity in BP and SF. Joint damage was estimated by hands and feet radiography. Larsen score and annual changes in LS were used for quantitative evaluation of joint destruction and radiographic progression of disease. MMP-9 activity in BP and SF was significantly higher in RA compared to controls, as well as in SF of patients with erosive compared to nonerosive RA. Faster radiographic progression and increased MMP-9 activity in BP and SF were detected in the group A (GA or AA genotype carriers) compared to the group G (GG genotype carriers). However, statistical significance was revealed only for MMP-9 activity in SF (p<0.05). MMP-9 activity in BP and SF is significantly higher in RA patients compared to patients with osteoarthritis. The presence of TNF-α-308A allele is associated with increased MMP-9 activity in SF of patients with early RA and may be a predictor of rapid radiographic progression of disease.

Association of CD8+ T-cells with bone erosion in patients with rheumatoid arthritis.

Bone erosion is a major problem worsening quality of rheumatoid arthritis (RA) patients' lives. However, causal factors responsible for bone erosion in RA have remained unclear. We aimed to examine genetic variants conferring bone erosion in RA using a Korean genome-wide association study (GWAS) and to search for possible biological mechanisms underlying the development of bone erosion. We obtained genome-wide single nucleotide polymorphism (SNP) data for 711 Korean RA patients using Illumina HapMap 550v3/660W arrays. Associations between SNPs and bone erosion status based on the Steinbrocker staging system were examined using multivariate logistic regression. Cell-type-specific enrichment of the epigenomic chromatin annotation H3K4me3 at the bone erosion associated variants was further investigated using National Institute of Health Roadmap Epigenomics data. As we tested the associations between 439 289 SNPs and bone erosion in 385 patients with erosive RA and 326 with non-erosive RA, none of the tested SNPs reached the genome-wide significance threshold, although many loci showed modest genetic effect on bone erosion status with suggestive association (e.g., rs2741200 [P = 3.75 × 10-6 ] in the SLA-TG locus and rs12422918 [P = 4.13 × 10-6 ] in SRGAP1). However, the top-ranked SNPs and their linked proxies, which were mostly located in non-coding variants, were significantly co-localized with the highly tissue-specific regulatory marker H3K4me3 in CD8+ memory T-cells (P = 0.014). Although, there was no large-effect variants associated with bone erosion in our GWAS, we have shown that CD8+ memory T-cells may have relevance with bone erosion in patients with RA through the analysis of ChiP-seq data.

Association of joint erosion with SLC22A4 gene polymorphisms inconsistently associated with rheumatoid arthritis susceptibility

Two single-nucleotide polymorphisms (SNPs) in SLC22A4 encoding an organic cation/zwitterion transporter protein, rs2073838 (commonly called slc2F1) and rs3792876 (slc2F2), had been associated with susceptibility to rheumatoid arthritis (RA) in two Japanese and one recent Chinese studies but not in other two Japanese and six Caucasian studies. In this study, the two SNPs were genotyped for 2313 Korean participants and their associations with RA susceptibility and severity were examined. SNP association with RA susceptibility was tested among 1304 RA patients and 1009 healthy controls, and association with joint erosion among 1063 erosive and 241 non-erosive RA patients. Meta-analysis for RA susceptibility association was additionally performed using 10 previous studies and the current one. The two SNPs were almost perfectly correlated with each other (r2 = 0.98), and therefore only slc2F1 was tested for association. RA susceptibility association was not found in Koreans (p = 0.93), but still significant in meta-analysis of six Asian studies including this Korean study (p = 0.00036, odds ratio = 1.1) or all 11 studies additionally including five Caucasian studies (p = 0.00021, odds ratio = 1.1). In contrast, an association was found for RA severity in Koreans. The minor allele A was marginally associated with 1.5-fold increased risk of joint erosion among RA patients afflicted for ≤11 years (p = 0.025) or ≤7 years (p = 0.029), though not among patients with longer-standing RA. Accordingly, SLC22A4 was associated with joint erosion in not-very-longstanding RA, although RA susceptibility association was weak and its clinical significance was uncertain.

Does non-erosive rheumatoid arthritis exist? A cross-sectional analysis and a systematic literature review

ObjectiveTo evaluate the prevalence and factors associated with non-erosive rheumatoid arthritis (RA). MethodsFirst, a cross-sectional analytical study was performed. Non-erosive disease, defined as the absence of any erosion on X-rays after 5 years of RA, was evaluated in 500 patients. Further and additional evaluations including ultrasonography (US) and computed tomography (CT) were performed in those patients meeting the eligibility criteria. The Spearman correlation coefficient, kappa analysis, and Kendall׳s W test were used to analyze the data. Second, a systematic literature review (SLR) was performed following the PRISMA guidelines. ResultsOf a total of 40 patients meeting the eligibility criteria for non-erosive RA, eight patients were confirmed to have non-erosive RA by the three methods. A positive correlation between non-erosive RA and shorter disease duration, antinuclear antibodies positivity, lower rheumatoid factor (RF) and C-reactive protein titers, lower global visual analog scale values, toxic exposures, and lower disease activity-(RAPID3) was found. In addition, an inverse correlation with anticyclic citrullinated peptide antibodies (ACPA) positivity and medication use was observed. From the SLR, it was corroborated that factors associated with this subphenotype were shorter disease duration, younger disease onset, negative ACPA and RF titers, low cytokine levels, and some genetic markers. ConclusionNon-erosive RA is rare, occurring in less than 2% of cases. These findings improve on the understanding of RA patients who present without erosions and are likely to have less severe disease.

Lymphopenia induced by etanercept

A 64-year-old woman (with a body mass index of 26) with seronegative nonerosive rheumatoid arthritis and biopsy-proven rheumatoid-associated lung disease presented to the clinic with lymphopenia. For the past 6 months, she has been taking prednisone, 20 mg/d, and leflunomide, 20 mg/d, each by mouth. She was treated previously for 2 years with methotrexate, adalimumab, and varying doses of prednisone, ranging from 5 to 20 mg/d. Six months ago, methotrexate treatment was discontinued for an open lung biopsy as was adalimumab treatment because of neuropathy. She subsequently received 5 doses of etanercept, 50 mg/wk, but this treatment was discontinued at her request secondary to injection site reactions.

FRI0513 Does non - erosive rheumatoid arthritis exist ?

BackgroundErosions are the hallmark of rheumatoid arthritis (RA). Although most of erosions may occur within 2 years of onset of the disease, their progression does not correlate with the duration...

Anti-Cyclic Citrullinated Peptide Antibody: An Early Diagnostic and Prognostic Biomarker of Rheumatoid Arthritis

To evaluate the role of Anti-Cyclic Citrullinated Peptide (anti-CCP) antibody and Rheumatoid Factor (RF) in Rheumatoid Arthritis (RA) patients. The present study comprised of 60 clinically diagnosed rheumatoid arthritis patients and 30 apparently healthy subjects as controls. Among 60 RA patients, 30 were <2 years duration and 30 were 3 to 15 years duration. Anti-CCP and RF levels were analyed by ELISA and immunoturbidimetric assay respectively. Disease activity was assessed by disease duration, duration of morning stiffness, hand deformity and radiological findings. Anti-CCP and rheumatoid factor were measured. A valid comparison showed that autoantibodies directed to citrullinated antigen-anti-CCP are superior to RF for the detection of RA. Anti-CCP antibodies have an independent role in predicting radiological damage and progression in RA patients. With their excellent specificity, anti-CCP antibodies can be used as serological marker in establishing the diagnosis of RA. Anti-CCP antibodies discriminated accurately between erosive and nonerosive RA making them a potentially good prognostic marker for the disease.

The 2010 ACR/EULAR classification criteria for rheumatoid arthritis in the Heinola inception cohort—diagnoses confirmed by long-term follow-up

The aim of this study was to evaluate the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for rheumatoid arthritis (RA) in a cohort with early arthritis and true diagnosis confirmed by long-term follow-up. The criteria were tested in the Heinola community-based inception cohort of 121 true RA patients, while the control group consisted of 95 patients with definite spondyloarthritis and swollen joint(s), recruited in the same time. The diagnoses were confirmed by long-term follow-up. The fulfillment of the four 2010 criteria was determined at baseline (arthritis duration less than 6months). Ninety-five in one hundred twenty-one (79%) of all RA patients, 54/68 (79%) of nonerosive (at baseline) RA patients, and 4/95 (4%) of controls fulfilled the 2010 criteria of RA, with better specificity (96%) than the 1987 ACR criteria (86%) in the same material. At baseline erosions were found in 44% of all RA patients and in 15% of the controls; rheumatoid factor was positive in 87% of the RA patients, but in 1% of the controls. One hundred seven in one hundred twenty-one (88%) of all RA patients and 16/95 (17%) of the controls fulfilled the 2010 total score criteria or were erosive at onset. The 2010 ACR/EULAR criteria should be documented in all patients with arthritis. If the criteria are not fulfilled at baseline in a nonerosive patient, the true diagnose may still be RA due to seroconversion or diagnostic manifestations during the follow-up. Indications for early disease modifying antirheumatic drug treatment may be present in active arthritis also in cases not fulfilling the new criteria at baseline.

Association of interleukin-4 receptor gene polymorphisms with rheumatoid arthritis in Egyptian female patients

Objectives The imbalance between proinflammatory and anti-inflammatory cytokines is a feature of rheumatoid arthritis (RA). The role of interleukin-4 (IL-4) and its receptor in the pathogenesis of RA is conflicting. We aim to investigate the role of polymorphisms in the IL-4Rα gene in susceptibility and severity of RA. Methods One hundred and seventy-two RA patients and 172 controls were enrolled in the study. Genotyping of IL-4Rα I50 V (rs1805010) and IL-4Rα Q576R (rs1801275) was determined by restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP). Results IL-4Rα I50 V genotype was significantly more frequent in patients with RA than in controls (OR: 1.97, 95% CI: 1–3.7, P: 0.035). Subjects with IL-4Rα V50 V genotype were significantly more likely to have erosive arthropathy (OR: 2.6, 95% CI: 1.1–6.1, P: 0.02). The frequencies of IL-4Rα Q576R genotype were significantly decreased in patients with erosive RA compared to patients with nonerosive RA (31.6% versus 48.2%, OR: 2.7, 95% CI: 1–7.7, P: 0.04). Conclusion IL-4Rα polymorphisms were associated with susceptibility to RA and may be helpful in early detection of erosive RA.