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ID PMID Title PublicationDate abstract
27313578 K/BxN Serum-Transfer Arthritis as a Model for Human Inflammatory Arthritis. 2016 The K/BxN serum-transfer arthritis (STA) model is a murine model in which the immunological mechanisms occurring in rheumatoid arthritis (RA) and other arthritides can be studied. To induce K/BxN STA, serum from arthritic transgenic K/BxN mice is transferred to naive mice and manifestations of arthritis occur a few days later. The inflammatory response in the model is driven by autoantibodies against the ubiquitously expressed self-antigen, glucose-6-phosphate isomerase (G6PI), leading to the formation of immune complexes that drive the activation of different innate immune cells such as neutrophils, macrophages, and possibly mast cells. The pathogenesis further involves a range of immune mediators including cytokines, chemokines, complement factors, Toll-like receptors, Fc receptors, and integrins, as well as factors involved in pain and bone erosion. Hence, even though the K/BxN STA model mimics only the effector phase of RA, it still involves a wide range of relevant disease mediators. Additionally, as a murine model for arthritis, the K/BxN STA model has some obvious advantages. First, it has a rapid and robust onset of arthritis with 100% incidence in genetically identical animals. Second, it can be induced in a wide range of strain backgrounds and can therefore also be induced in gene-deficient strains to study the specific importance of disease mediators. Even though G6PI might not be an essential autoantigen, for example, in RA, the K/BxN STA model is a useful tool to understand how autoantibodies, in general, drive the progression of arthritis by interacting with downstream components of the innate immune system. Finally, the model has also proven useful as a model wherein arthritic pain can be studied. Taken together, these features make the K/BxN STA model a relevant one for RA, and it is a potentially valuable tool, especially for the preclinical screening of new therapeutic targets for RA and perhaps other forms of inflammatory arthritis. Here, we describe the molecular and cellular pathways in the development of K/BxN STA focusing on the recent advances in the understanding of the important mechanisms. Additionally, this review provides a comparison of the K/BxN STA model to some other arthritis models.
27431345 Autoantibodies in Sjögren's Syndrome. 2016 Aug We compiled information on antibodies in Sjögren syndrome, focusing more on clinical manifestations associated with anti-Ro/SSA and anti-La/SSB antibodies and studies regarding novel antibodies. We reviewed previous as well as most recent studies with the subject heading Sjogren in combination with antibodies and congenital heart block (CHB). Almost half of asymptomatic mothers giving birth to children with CHB ultimately develop Sjögren. We discussed studies concerning the presence of antibodies predating clinical manifestations of disease. Studies in the future are required to ascertain the pathogenic mechanisms associated with these antibodies and the specific clinical manifestation related to new autoantibodies.
27433576 Lipid-Core Nanocapsules Improved Antiedematogenic Activity of Tacrolimus in Adjuvant-Induc 2016 Feb Despite significant technological advances, rheumatoid arthritis remains an incurable disease with great impact on the life quality of patients. We studied the encapsulation of tacrolimus in lipidcore nanocapsules (TAC-LNC) as a strategy to enhance its systemic anti-arthritic properties. TAC-LNC presented unimodal distribution of particles with z-average diameter of 212 +/- 11, drug content close to the theoretical value (0.80 mg mL(-1)), and 99.43% of encapsulation efficiency. An in vitro sustained release was determined for TAC-LNC with anomalous transport mechanism (n = 0.61). In vivo studies using an arthritis model induced by Complete Freund's Adjuvant demonstrated that the animals treated with TAC-LNC presented a significantly greater inhibition of paw oedema after intraperitoneal administration. Furthermore, the encapsulation of TAC in lipid-core nanocapsules was potentially able to prevent hyperglycemia in the animals. In conclusion, TAC-LNC was prepared with 100% yield of nanoscopic particles having satisfactory characteristics for systemic use. This formulation represents a promising strategy to the treatment of rheumatoid arthritis in the near future.
27446536 A protocol for the culture and isolation of murine synovial fibroblasts. 2016 Aug The culture of synovial fibroblasts (SFs) is one of the most effective tools for investigating the pathology and physiology of synovial tissues and should prove useful for identifying the importance of SFs in disease as well as for the development of novel therapeutic approaches for several chronic joint diseases, such as rheumatoid arthritis. However, thus far, a detailed protocol for the primary culture and isolation of murine SFs has not been established. Therefore, the present study describes an easy and convenient method for isolating and culturing SFs from C57BL/6 mice. This protocol can be divided into 4 stages: Isolation of synovial tissues, isolation of SFs, seeding of SFs for growth in culture and purity analysis of SFs using the four cell markers, vimentin, cluster of differentiation 90.2 (CD90.2; Thy-1.2), intracellular adhesion molecule 1 (CD54) and vascular cell adhesion molecule 1 (CD106). This method is efficient and a purified population of SFs can be obtained 10 days after the initiation of culture.
29259681 GM-CSF as a therapeutic target in autoimmune diseases. 2016 Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been known as a hematopoietic growth factor and immune modulator. Recent studies revealed that GM-CSF also had pro-inflammatory functions and contributed to the pathogenicity of Th17 cells in the development of Th17-mediated autoimmune diseases. GM-CSF inhibition in some animal models of autoimmune diseases showed significant beneficial effects. Therefore, several agents targeting GM-CSF are being developed and are expected to be a useful strategy for the treatment of autoimmune diseases. Particularly, in clinical trials for rheumatoid arthritis (RA) patients, GM-CSF inhibition showed rapid and significant efficacy with no serious side effects. This article summarizes recent findings of GM-CSF and information of clinical trials targeting GM-CSF in autoimmune diseases.
27259064 Recent advances of exosomes in immune modulation and autoimmune diseases. 2016 Sep Exosomes are small membrane-bound vesicles (30-100 nm) that are secreted by different types of cells and they have been well documented to resemble saucers or flattened spheres under the electron microscope. Recently, evidence indicates that exosomes play important roles in the immune modulation and are associated with the immune pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA), Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE). In this review, we will summarize current research advances of exosomes in immunoregulation, pathogenesis, diagnosis and therapeutics of autoimmune diseases.
25819235 Biosimilars: a systematic review of published and ongoing clinical trials of antipsoriatic 2015 Apr Biosimilars for psoriasis treatment are currently being developed. Comparison of their efficacy and safety is a challenge. For approval, the European Medicines Agency (EMA) considers indirect evidence from other indications (for example, rheumatoid arthritis) as sufficient. Systematic review of biosimilars for psoriasis and other indications, review of ongoing trials in trial registers. Systematic search for randomized controlled trials (RCT) on biosimilars to adalimumab, etanercept, infliximab, and ustekinumab compared to their reference medication: (1) Publications in Medline, Medline In-Process, Embase, Cochrane Library (efficacy, safety, immunogenicity) and (2) ongoing studies in clinical trial registers. No trials on biosimilars in psoriasis patients were identified. As to the infliximab biosimilar, there is data on patients with ankylosing spondylitis and rheumatoid arthritis, indicating no clinically relevant differences regarding efficacy and safety. Currently, there are two registered studies of an adalimumab biosimilar and one study of an etanercept biosimilar in psoriasis patients. Further ongoing studies on biosimilars to adalimumab, etanercept, and infliximab - all in rheumatoid arthritis patients - were identified. There is currently only limited data regarding RCTs with biosimilars. Provision of further clinical data and inclusion of patients in patient registers will be crucial.
27289467 The Role of Sirtuins in Cartilage Homeostasis and Osteoarthritis. 2016 Jul The past decade has witnessed many advances in the understanding of sirtuin biology and related regulatory circuits supporting the capacity of these proteins to serve as energy-sensing molecules that contribute to healthspan in various tissues, including articular cartilage. Hence, there has been a significant increase in new investigations that aim to elucidate the mechanisms of sirtuin function and their roles in cartilage biology, skeletal development, and pathologies such as osteoarthritis (OA), rheumatoid arthritis (RA), and intervertebral disc degeneration (IVD). The majority of the work carried out to date has focused on SIRT1, although SIRT6 has more recently become a focus of some investigations. In vivo work with transgenic mice has shown that Sirt1 and Sirt6 are essential for maintaining cartilage homeostasis and that the use of sirtuin-activating molecules such as resveratrol may have beneficial effects on cartilage anabolism. Current thinking is that SIRT1 exerts positive effects on cartilage by encouraging chondrocyte survival, especially under stress conditions, which may provide a mechanism supporting the use of sirtuin small-molecule activators (STACS) for future therapeutic interventions in OA and other degenerative pathologies of joints, especially those that involve articular cartilage.
27957720 (99m)Tc-labelled S-HYNIC certolizumab pegol in rheumatoid arthritis and spondyloarthritis 2016 Dec BACKGROUND: Biologicals directed against tumour necrosis factor (TNF) have proven their efficacy in the treatment of spondyloarthritis and rheumatoid arthritis. We present a radiolabelling method for certolizumab pegol (CZP), a commercially available humanized Fab'-fragment directed against TNF. A biodistribution and dosimetry study was conducted. Tc-S-HYNIC CZP was synthesized. The in vitro TNF neutralizing activity was tested by exposing L929s-cells to various concentrations 99mTc-S-HYNIC CZP and measuring TNF-induced cytotoxicity. For biodistribution and dosimetry, WB images and blood and urine sampling were performed up to 24 h pi. Cumulative activities were estimated using mono-exponential fitting, and organ doses were estimated using OLINDA/EXM. The effective dose was calculated using the International Commission on Radiological Protection 103 recommendations. The uptake of the tracer in the peripheral joints was assessed visually and semiquantitatively. RESULTS: In vitro tests showed blocking of TNF cytotoxicity by the (99m)Tc-S-HYNIC CZP formulation comparable to the effect obtained with the unlabelled CZP with or without the HYNIC linker. We analysed eight patients with rheumatoid arthritis or spondyloarthritis. The highest mean absorbed organ doses were recorded for kidneys, spleen, and liver: 56 (SD 7), 34 (SD 6), and 33 (SD 7) μGy/MBq. The effective dose was 6.1 (SD 0.9) mSv for a mean injected activity of 690 (SD 35) MBq. The urinary excretion was 15.1% (SD 8.1) of the IA at 22.5 h. Blood analysis yielded a distribution half-life of 1.2 h (SD 1.5) and an elimination half-life of 26.9 h (SD 2.7). Visual analysis of the scans revealed marked tracer accumulation in the clinically affected peripheral joints. In addition, there was a statistically significant higher uptake of the tracer in the swollen joints (median uptake ratio compared to background of 3.3 in rheumatoid arthritis and 2.4 in peripheral spondyloarthritis) compared to clinically negative joints (respectively 1.3 and 1.6). CONCLUSIONS: We present a radiolabelling technique for CZP, a Fab'-fragment directed against TNF and currently used as a therapeutic agent in rheumatology. An effective dose of 6.1 mSv (SD 0.9) was estimated. We confirmed the uptake of this new radiopharmaceutical in clinically affected peripheral joints.
27259576 Somatostatin receptor scintigraphy in patients with rheumatoid arthritis and secondary Sjà 2016 Dec BACKGROUND: Human T lymphocytes infiltrating tissues in autoimmune diseases are known to express somatostatin receptors amongst other activation markers. In this study, we evaluated whether somatostatin receptor scintigraphy (SRS) using a radiolabelled somatostatin analogue ((99m)Tc-EDDA/tricine-HYNIC-tyr(3)-octreotide ((99m)Tc-EDDA/HYNIC-TOC)) is able to detect the presence of immune-mediated processes in patients with rheumatoid arthritis and secondary Sjögren's syndrome. We also aimed to evaluate whether positivity to SRS was predictive of therapeutic response and if SRS could be used for monitoring the efficacy of immunomodulatory treatment. METHODS: Eighteen patients with rheumatoid arthritis and secondary Sjögren's syndrome not responding to conventional treatment were recruited for treatment with infliximab, a monoclonal antibody against TNF-α. All patients had complete blood cell count, renal and liver function tests, measurements of ESR, CRP, ANA, ENA, and anti-dsDNA antibodies, functional salivary gland scintigraphy, labial biopsy, and ophthalmologic assessment with Schirmer's test and tear film break-up time (BUT). Diagnosis was made according to the revised criteria of the American-European Consensus Group. All patients underwent SRS at baseline and after 3-6 months of therapy with infliximab. Eleven out of 18 had repeat SRS images. Images of the salivary glands and major joints were acquired 3 h after injection of 370 MBq of (99m)Tc-EDDA/HYNIC-TOC. Image analysis was performed semi-quantitatively. RESULTS: All patients showed uptake of (99m)Tc-EDDA/HYNIC-TOC in the joints. Salivary glands also showed variable radiopharmaceutical uptake in 12 out of 18 patients, but all patients showed presence of lymphocytic infiltration at labial salivary gland biopsy. All patients, who repeated the study after treatment, showed significant reduction of somatostatin uptake in the joints but not in the salivary glands. CONCLUSIONS: SRS using (99m)Tc-EDDA/HYNIC-TOC may be a useful imaging tool to assess disease activity and extent in patients with rheumatoid arthritis and may help to detect secondary Sjögren's syndrome. It may also aid therapy decision-making with anti-TNFα antibodies in the joints but not in salivary glands.
26420920 Modelling and Characterization of Glial Fibrillary Acidic Protein. 2015 Glial Fibrillary Acidic Protein (GFAP) is an intermediate-filament (IF) protein that maintains the astrocytes of the Central Nervous System in Human. This is differentially expressed during serological studies in inflamed condition such as Rheumatoid Arthritis (RA). Therefore, it is of interest to glean molecular insight using a model of GFAP (49.88 kDa) due to its crystallographic nonavailability. The present study has been taken into consideration to construct computational protein model using Modeller 9.11. The structural relevance of the protein was verified using Gromacs 4.5 followed by validation through PROCHECK, Verify 3D, WHAT-IF, ERRAT and PROVE for reliability. The constructed three dimensional (3D) model of GFAP protein had been scrutinized to reveal the associated functions by identifying ligand binding sites and active sites. Molecular level interaction study revealed five possible surface cavities as active sites. The model finds application in further computational analysis towards drug discovery in order to minimize the effect of inflammation.
27190682 Ultrasound Assessment of Synovial Thickness of Some of the Metacarpophalangeal Joints of H 2016 Objective. To compare ultrasound synovial thickness of the 2nd, 3rd and 4th metacarpophalangeal joints (MCPJ) in a group of patients with proven rheumatoid arthritis (RA) and a control group of normal individuals. Materials and Methods. This is a cross-sectional study comprising 30 rheumatoid arthritis patients and 30 healthy individuals. Ultrasound scans were performed at the dorsal side of 2nd, 3rd, and 4th MCPJ of both hands in RA patients and the healthy individuals. Synovial thickness was measured according to quantitative method. The synovial thickness of RA patients and healthy individuals was compared and statistical cut-off was identified. Results. Maximum synovial thickness was most often detected at the radial side of the 2nd MCPJ and 3rd MCPJ and ulnar side of the 4th MCPJ of both hands which is significantly higher (p < 0.05) in RA patients compared to healthy individuals. With high specificity (96%) and sensitivity (90%) the optimum cut-off value to distinguish RA patients and healthy individuals' synovial thickness differs for the radial side of the 2nd and 3rd MCPJ and ulnar side of the 4th MCPJ. Conclusion. Patients with early RA appear to exhibit a characteristic pattern of synovitis which shows radial side predominance in the 2nd and 3rd MCPJ and ulnar side in the 4th MCPJ.
26834751 Tregalizumab - A Monoclonal Antibody to Target Regulatory T Cells. 2016 Regulatory T cells (Tregs) represent a subpopulation of CD4(+) T cells, which are essential for the maintenance of immunological tolerance. The absence or dysfunction of Tregs can lead to autoimmunity and allergies. The restoration of functional Tregs and/or Treg cell numbers represents a novel and attractive approach for the treatment of autoimmune diseases, e.g., rheumatoid arthritis (RA). The CD4 cell surface receptor is a target for modulation of T cell function. Monoclonal antibodies (mAbs) against CD4 have previously been tested for the treatment of autoimmune diseases, including RA. Furthermore, in model systems, anti-CD4 antibodies are able to induce tolerance and mediate immunomodulatory effects through a variety of mechanisms. Despite the availability of innovative and effective therapies for RA, many patients still have persistently active disease or experience adverse events that can limit use. A growing body of evidence suggests that Treg modulation could offer a new therapeutic strategy in RA and other autoimmune disorders. Here, we describe tregalizumab (BT-061), which is a novel, non-depleting IgG1 mAb that binds to a unique epitope of CD4. Tregalizumab represents the first humanized anti-CD4 mAb that selectively induces Treg activation.
26509049 Glucocorticoid-induced osteoporosis. 2015 Corticosteroid-induced osteoporosis is the most common form of secondary osteoporosis and the first cause in young people. Bone loss and increased rate of fractures occur early after the initiation of corticosteroid therapy, and are then related to dosage and treatment duration. The increase in fracture risk is not fully assessed by bone mineral density measurements, as it is also related to alteration of bone quality and increased risk of falls. In patients with rheumatoid arthritis, a treat-to-target strategy focusing on low disease activity including through the use of low dose of prednisone, is a key determinant of bone loss prevention. Bone loss magnitude is variable and there is no clearly identified predictor of the individual risk of fracture. Prevention or treatment of osteoporosis should be considered in all patients who receive prednisone. Bisphosphonates and the anabolic agent parathyroid hormone (1-34) have shown their efficacy in the treatment of corticosteroid-induced osteoporosis. Recent international guidelines are available and should guide management of corticosteroid-induced osteoporosis, which remains under-diagnosed and under-treated. Duration of antiosteoporotic treatment should be discussed at the individual level, depending on the subject's characteristics and on the underlying inflammation evolution.
27092274 Amtolmetin: A Reappraisal of NSAID with Gastroprotection. 2016 Aim. To assess the gastrosparing effect of amtolmetin guacyl (AMG) against other nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with osteo-/rheumatoid arthritis. Methods. A literature search was done in the electronic databases (PubMed, Google Scholar, Embase, and Scopus) with key words "amtolmetin guacyl", "amtolmetin", and "arthritis"; filters were applied to obtain publications between 01-Jan-1985 and 01-Oct-2015, which were "clinical trials" in osteo-/rheumatoid arthritis patients and in "English language." Studies were assessed using the Jadad criteria and trials with score ≥ 3 were included in the analysis to compare the safety and efficacy of AMG against other NSAIDs. Results. Search yielded 19 publications of which 3 were included for analysis. Baseline characteristics of patients were comparable between the AMG group and other NSAIDs (diclofenac, celecoxib, and piroxicam) groups in all trials. Efficacy of AMG was similar to the other NSAIDs compared in the trials. The number of adverse events (AEs) reported was similar between both the groups; however, severe AEs reported were significantly lower in the AMG group. Of note was the significant lower number of duodenal ulcers after treatment in the AMG group. Conclusions. AMG has efficacy similar to other NSAIDs and a safer gastrointestinal AE profile when compared to the other NSAIDs.
25440705 [Comparison of the Disease Activity Score-28 and Juvenile Arthritis Disease Activity Score 2015 Jan INTRODUCTION: the assessment of the activity of rheumatoid arthritis and juvenile idiopathic arthritis is made by means of different tools, respectively DAS-28 and JADAS. OBJECTIVE: To compare DAS-28 and JADAS with scores of 71, 27 and 10 joint counts in juvenile idiopathic arthritis. METHOD: A secondary analysis of a phase III placebo-controlled trial, testing safety and efficacy of abatacept was conducted in 8 patients with 178 assessment visits. Joint count scores for active and limited joints, physician's and parents' global assessment by 0-10cm Visual Analog Scale, and erythrocyte sedimentation rate normalized to 0-10 scale, in all visits. The comparison among the activity indices in different observations was made through Anova or adjusted gamma model. The paired observations between DAS-28 and JADAS 71, 27 and 10, respectively, were analyzed by linear regression. RESULTS: There were significant differences among individual measures, except for ESR, in the first four months of biological treatment, when five of the eight patients reached ACR-Pedi 30, with improvement. The indices of DAS-28, JADAS 71, 27 and 10 also showed significant difference during follow-up. Linear regression adjusted model between DAS-28 and JADAS resulted in mathematical formulas for conversion: [DAS-28=0.0709 (JADAS 71)+1.267] (R(2)=0.49); [DAS-28=0.084 (JADAS 27) +1.7404] (R(2)=0.47) and [DAS-28=0.1129 (JADAS-10) +1.5748] (R(2)=0.50). CONCLUSION: The conversion of scores of DAS-28 and JADAS 71, 27 and 10 for this mathematical model would allow equivalent application of both in adolescents with arthritis.
27104116 The count of tender rather than swollen joints correlates with aortic stiffness in patient 2016 BACKGROUND: Patients with rheumatoid arthritis (RA) are at a higher cardiovascular (CV) risk in comparison to the general population. CV risk associates closely with aortic stiffness. Aim of this exploration was therefore to evaluate aortic stiffness in patients with RA and to examine its association with various RA associated parameters as well as with traditional CV risk factors. METHODS: Measurements of carotid-femoral pulse wave velocity (cfPWV) were analyzed retrospectively in 38 RA patients and 25 controls. We investigated the statistical difference between cfPWV values in the two groups. Furthermore, we analyzed the associations of cfPWV with laboratory and clinical RA parameters including Disease Activity Score 28 and its components, rheumatoid factor, cyclic citrullinated peptide antibodies, antinuclear antibodies and RA duration. Finally, we explored the relationship of cfPWV with traditional CV risk factors in the RA group. RESULTS: cfPWV was not significantly higher in RA patients in comparison to controls in an adjusted statistical model for confounding factors [-0.587 95 % CI (-1.38 to 0.201), p = 0.144]. Among RA patients there was a statistically significant correlation of cfPWV with age (rho = 0.544, p = 0.001) and the count of tender joints [0.051 95 % CI (0.008-0.207), p = 0.034]. Finally, C-reactive protein associated only marginally with cfPWV [0.105 95 % CI (-0.410 to 0.003), p = 0.053]. CONCLUSIONS: In RA patients the number of tender, rather than swollen joints correlates with stiffness of the aorta, as measured through cfPWV. Therefore, RA associated joint pain might play a role in the development of aortic stiffness and thus increase CV risk.
27994266 Secretory activity of subcutaneous abdominal adipose tissue in male patients with rheumato 2016 INTRODUCTION: Adipose tissue exerts widespread effects on the metabolism and immune system, but its activity differs between the genders. In the general population low-grade adipose tissue inflammation contributes to development of diseases of affluence. Little is known about the systemic impact of peripheral fat tissue in osteoarthritis (OA) and rheumatoid arthritis (RA), characterized by chronic, low- and high-grade systemic inflammation, respectively. To clarify this we evaluated the secretory activity of subcutaneous abdominal adipose tissue (SAAT) obtained from male patients affected with RA (n = 21) and OA (n = 13), and assessed its association with body mass and composition, demographic, clinical and laboratory data. MATERIAL AND METHODS: Basal and interleukin (IL)-1β-triggered secretion of selected adipocytokines from SAAT explants was measured by specific enzyme-linked immunosorbent assays (ELISA). Patients' body composition was evaluated by bioelectric impendence technique. RESULTS: Rheumatoid SAAT secreted more adiponectin and macrophage migration inhibitory factor (MIF) than respective osteoarthritis tissue. In both RA and OA patient groups, stimulation of SAAT explants with IL-1β (1 ng/ml/100 mg tissue) significantly up-regulated release of pro-(IL-6, IL-8, tumor necrosis factor - TNF) and anti-inflammatory (IL-10) cytokines but had no effect on the secretion of adiponectin, leptin, MIF and hepatocyte growth factor (HGF). Compared with RA, patients with OA were more obese. In RA patients SAAT-released adiponectin and TNF inversely correlated with body mass index (BMI) and visceral fat rating (FVSC). In addition, SAAT-secreted adiponectin and leptin positively correlated with DAS28 and disease duration, respectively. In the OA group tissue-released TNF positively correlated with patients' age. CONCLUSIONS: We conclude that in RA male patients adipocytokines originating from SAAT are of clinical importance because: (i) adiponectin and TNF may contribute to maintenance of normal body composition and mass, (ii) in addition adiponectin may play a pathogenic role. Moreover, in both RA and OA male patients secretory activity of SAAT may vary with time.
28352702 Platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in patients with rheumatoi 2015 OBJECTIVES: It has been well documented that the platelet to lymphocyte ratio (PLR) and the neutrophil to lymphocyte ratio (NLR) are associated with outcomes for patients with gastric cancer, non-small cell lung cancer and acute heart failure. Inflammation may be the hidden factor that explains the correlation between NLP, PLR, and these diseases. However, to date, the data concerning NLR, PLR, and its association with inflammation are lacking in patients with rheumatoid arthritis (RA), thus, our aim to discuss whether NLR and PLR are associated with RA. METHODS: Patients with RA and healthy individuals were included according to the determined criteria, and laboratory indicators were measured. RESULTS: PLR and NLR were significantly higher in RA patients compared with healthy controls (3.20±2.06 vs. 1.56±0.47, P<0.01; 192.85±101.78 vs. 103.49±28.68, P<0.01). When leukocytes, neutrophil percentage, neutrophil, lymphocyte, platelet, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were considered as confounders (crude model), our results indicated that ESR and RF were correlated to RA. Of note, ESR, RF, and PLR were associated with RA after further adjustment based on crude model for PLR and NLR. Receiver operating characteristic (ROC) curves analysis showed that PLR values higher than >115.7 evaluated RA with a sensitivity of 82.5%, a specificity of 74.8% and area under the curve ( AUC ) of 0.847. CONCLUSIONS: Our results suggest that PLR is associated with RA, and PLR may be an underlying indicator indicating the chronic subclinical inflammation in patients with RA.
28352685 Relation between bone mineral density and IL-17 serum levels in Serbian patients with earl 2015 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and destruction of joint cartilage and bone. Different cytokines play important role in the processes that cause articular destruction and extra-articular manifestations in RA. The contribution of cytokines representing the Th1 (INF-γ), Th2 (IL-4) and IL-17A to the pathogenesis of early RA and bone mineral density (BMD) loss in still poorly understood. Serum samples of 38 early RA patients were evaluated for erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP) and for the tested cytokines (IL-17A, IL-4 and INF-γ). BMD was evaluated by dualenergy X-ray absorptiometry (DXA). Disease activity score (DAS28) calculation was assessed for all patients. Control serum samples were obtained from 34 healthy volunteers. The levels of tested cytokines were significantly higher (IL-17A, p<0.001; INF-γ, P<0.001; IL-4, P<0.01) in patients with early RA, compared to the healthy controls. In early RA patients, strong correlation of serum IL-17A was found with DAS28, ESR and CRP. Also, a significant negative correlation was found between serum INF-γ levels and the DAS28 score. Significantly positive correlation of BMD values and CRP, DAS28 IL-17A were also demonstrated. DXA analysis revealed that the most common site for osteoporosis was the lumbar spine followed by the femoral neck. BMD values significantly correlated with CRP, DAS28 score and IL-17A serum levels. The mean serum IL-17A levels, in patients with early RA, corresponded with disease activity, severity and BMD loss, indicating the potential usefulness of serum IL-17A in defining the disease activity and bone remodeling.