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ID PMID Title PublicationDate abstract
20191524 Association between computer use speed and age, impairments in function, and touch typing 2010 Feb OBJECTIVE: To explore the associations between impairments in hand function associated with rheumatoid arthritis (RA) and limitations in computer peripheral use. METHODS: A total of 45 computer users with RA were recruited from the Arthritis Network Research Registry. Impairments in hand function were measured using the Keitel Hand Function Index, and the Arthritis Hand Function Test, while general activity limitations were measured with the Health Assessment Questionnaire. Speed of computer peripheral device use was obtained at a laboratory work station using the Assessment of Computer Task Performance (ACTP). RESULTS: Multiple regression models suggested that keyboarding speed was significantly associated with touch typing training and age, while mouse speed was significantly associated with age. Impairments in hand function were significantly associated with only 2 of 7 keyboarding tasks and no mouse tasks. General activity limitations were associated with 2 of 7 keyboarding tasks and 2 of 5 significant mouse tasks. A comparison of this study's sample with a normative sample reported for the ACTP suggested that this sample's keyboarding speed was similar to a nonimpaired sample, while mouse speed was much slower. CONCLUSION: Reduced keyboarding speed is most strongly associated with touch typing skill. General activity limitations appear to be the strongest arthritis-related predictor of decreased computer use speeds. Many computer users with RA will not experience reduced productivity in typing speeds, although many may be slower than their nonimpaired counterparts for mouse use.
20740387 Laboratory tests in pediatric rheumatology. 2010 Sep Laboratory tests in rheumatology are important tools that help to support the diagnosis of autoimmune diseases, evaluate the disease activity, monitor the side effects of therapy, and also assist the physician to exclude rheumatologic mimics. Few relevant tests should be ordered after a detailed clinical review of the patient has been carried out and a provisional clinical diagnosis has been reached. There is no test that can rule in or rule out any rheumatologic disease and therefore, there is no role of a detailed "Rheumatology panel" of investigations. In this review, routine blood investigations, acute phase reactants, auto antibodies, HLA B27 and complements have been discussed.
21045184 Use of tomosynthesis for erosion evaluation in rheumatoid arthritic hands and wrists. 2011 Jan PURPOSE: To compare tomosynthesis with radiography for the detection of hand and wrist bone erosions in patients with rheumatoid arthritis (RA), using multidetector computed tomography (CT) as the reference method. MATERIALS AND METHODS: The study was approved by the local ethics committee, and written consent was obtained from all patients. From December 2008 to April 2009, 30 consecutive patients with RA were included in this prospective study. They underwent radiography, tomosynthesis, and CT of the most symptomatic hand and wrist on the same day. Two radiologists and one rheumatologist independently read images from the three imaging modalities. RESULTS: A total of 232 erosions were detected with CT, while 199 and 140 erosions, respectively, were detected with tomosynthesis and radiography. More erosions were revealed with CT than with tomosynthesis and radiography (P < .0001); significantly more erosions were shown with tomosynthesis than with radiography (P < .0001). With CT as the reference method for bone erosions, the overall sensitivity, specificity, and accuracy of tomosynthesis were, respectively, 77.6%, 89.9%, and 83.1%. The corresponding values for radiography were 53.9%, 92%, and 70.9%. The sensitivity of each reader increased by roughly 20% with use of tomosynthesis. CONCLUSION: The depiction of bone erosions of the hands and wrists is significantly greater with tomosynthesis than with radiography.
19174154 Metabolism-blocked antifolates as potential anti-rheumatoid arthritis agents: 4-amino-4-de 2009 Apr 1 4-Amino-4-deoxy-5,8,10-trideazapteroyl-d,l-4'-methyleneglutamic acid (CH-1504) is the prototype of a potentially therapeutically more selective class of antifolates for rheumatoid arthritis treatment. This class is characterized by retention of dihydrofolate reductase (DHFR; EC 1.5.1.3) as their locus of action and transport by the reduced folate carrier (RFC; SLC19A1), but their lack of metabolism by known pathways of antifolate (e.g., methotrexate (MTX)) metabolism. Five new CH-1504 analogs (CHL-001-CHL-005) were synthesized and diastereomers of CH-1504 itself were obtained by preparative chiral HPLC; all were characterized biochemically. The analogs are not metabolized by aldehyde oxidase (EC 1.2.3.1), carboxypeptidase G2 (EC 3.4.17.11), or (excepting CHL-003) folylpolyglutamate synthetase (EC 6.3.2.17) and thus, unlike MTX, are "metabolism-blocked". All analogs are potent DHFR inhibitors; several are nearly as potent as MTX or CH-1504. Each analog uses the RFC for transport, although with varying apparent affinities. In contrast, each weakly inhibits other enzymes of folate metabolism relevant to rheumatoid arthritis therapy (thymidylate synthase (EC 2.1.1.45), two formyltransferases of purine biosynthesis (EC 2.1.2.2 and EC 2.1.2.3), and 5,10-methylenetetrahydrofolate reductase (EC 1.5.1.20)). Biochemical characterization showed one 4'-diastereomer of racemic CH-1504 was significantly more active than the other. Based on literature data concerning the effect of d- and l-glutamic acid substitution on antifolate activity, it is likely that the diastereomer containing l-4'-methylene-glutamic acid is the more active. Because of concern about potential pharmacokinetic and biochemical effects of d-4'-methylene-glutamic acid-containing species, these data suggest that future analogs should contain only l-4'-methylene-glutamic acid. Overall, these data provide several interesting new leads for preclinical development.
20108012 Group visits for rheumatoid arthritis patients: a pilot study. 2010 Jun This pilot study explored the feasibility of a group visit model for patients with rheumatoid arthritis (RA) and for medical staff at a private practice. RA patients were invited to attend six 3.5-h-long group visit sessions held once per month at a wellness center. Each included group discussion, individual patient examinations, interactive question, and answer periods, and topic-specific presentations from various health professionals. Nineteen of the 24 RA patients invited to the group visits agreed to attend, and 13 to 15 were present at any given session. Participants expressed a high level of satisfaction in evaluation forms completed at the end of the last session. Group visits allowed the rheumatologist to spend more time providing advice for various health issues and eliminated the need to repeat advice about common issues. This group visit model is feasible for motivated RA patients who can meet the time commitment involved.
20864145 Hand radiological damage in systemic sclerosis: comparison with a control group and clinic 2011 Apr OBJECTIVE: To define the burden of hand radiological damage in systemic sclerosis (SSc) patients, compared with a control group. METHODS: Both hands of 167 SSc patients and 168 hands (82 right and 86 left) of age- and gender-matched controls were imaged by conventional radiograph. Two musculoskeletal radiologists semiquantitatively scored the following lesions: tuft acro-osteolysis, tuft calcinosis, joint space narrowings, marginal erosions, surface erosions, collapse arthropathies, periarticular calcifications, and juxta-articular osteoporosis, at the following areas: tufts, distal interphalangeal, proximal interphalangeal, metacarpophalangeal, carpal, and first carpometacarpal joints. Clinical and functional characteristics of the 167 SSc patients were obtained from the Belgian Systemic Sclerosis Cohort database. RESULTS: Tuft acro-osteolysis and calcinosis were the most common findings observed in SSc patients and were almost absent in controls. SSc patients displaying tuft acro-osteolysis/calcinosis suffered from more severe disease. Arthropathies were infrequently detected and mainly consisted of a mixture of osteoarthritis-related changes (joint space narrowing and surface erosions)-also observed in controls-and of 2 types of rare SSc-associated arthropathies: a rheumatoid arthritis-like pattern, characterized by marginal erosions (n = 7 patients), and a collapse arthropathy (n = 6 patients), characterized by pressure erosions and joint subluxation. CONCLUSIONS: Although a rheumatoid arthritis-like or a collapse arthropathy can be observed in SSc patients, arthropathies are less common than previously reported.
19117368 Transfer of the shared epitope through microchimerism in women with rheumatoid arthritis. 2009 Jan OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease that affects mostly women and is associated with HLA-DRB1 genes having in common a shared epitope sequence. In parallel, cells and/or DNA originating from pregnancy (microchimerism) persist for decades and could contribute to autoimmunity. The aim of this study was to examine whether microchimerism may be a source of the shared epitope among women with RA. METHODS: Women with RA and healthy women who lacked RA-associated genes such as HLA-DRB1*01 (n=33 and n=46, respectively) and/or HLA-DRB1*04 (n=48 and n=64, respectively), were tested for DRB1*01 or DRB1*04 microchimerism by HLA-specific quantitative polymerase chain reaction assays. As controls, alleles not associated with RA (DQB1*02 and DRB1*15/16) were also analyzed. RESULTS: Compared with healthy women, women (42% with RA had a higher frequency and higher levels of DRB1*04 microchimerism versus 8%; P=0.00002) as well as DRB1*01 microchimerism (30% versus 4%; P=0.0015). Moreover, no difference in microchimerism was observed for alleles not associated with RA. CONCLUSION: Women with RA had microchimerism with RA-associated HLA alleles, but not with non-RA-associated HLA alleles, more often and at higher levels compared with healthy women. These observations are the first to indicate that microchimerism can contribute to the risk of an autoimmune disease by providing HLA susceptibility alleles.
19536547 Diffuse lupus encephalopathy in a case of rhupus syndrome. 2010 May "Rhupus syndrome" is a rare clinical condition, which is related to anti-CCP antibody, characterized by overlapping clinical and immunologic features of rheumatoid arthritis and systemic lupus erythematosus. Previous reports mentioned that patients have more RA-associated damage, and little organic damage associated with SLE. The severe organ damage, especially central nervous system involvement has been reported to be rare in patients with rhupus syndrome. Here, we report a very rare concurrence of RA, SLE and diffuse lupus encephalopathy in a Chinese woman.
20213803 Deletion of the late cornified envelope genes, LCE3C and LCE3B, is associated with rheumat 2010 May OBJECTIVE: The risk of rheumatoid arthritis (RA) is increased in the offspring of individuals affected with various autoimmune disorders, including psoriasis. Recently, the deletion of 2 genes from the late cornified envelope (LCE) gene cluster, LCE3C and LCE3B, has been associated with psoriasis in several populations. The purpose of this study was to assess whether this polymorphic gene deletion could also be involved in susceptibility to RA. METHODS: We tested for association between the LCE3C_LCE3B copy number variant and a single-nucleotide polymorphism in strong linkage disequilibrium with this variant (rs4112788) and RA in 2 independent case-control data sets (197 and 400 samples from patients with RA, respectively, and 411 and 567 samples from control subjects, respectively), collected at 4 Spanish hospitals. All samples were directly typed for presence of the LCE3C_LCE3B deletion (LCE3C_LCE3B-del) by polymerase chain reaction, and association analysis was performed using the SNPassoc R package. RESULTS: An association of homozygosity for the LCE3C_LCE3B-del and rs4112788 C allele with the risk of RA was observed in the first data set and was replicated in an independent case-control set. A combined analysis showed an overall P value of 0.0012 (odds ratio [OR] 1.45, 95% confidence interval [95% CI] 1.16-1.81) for association of the LCE3C_LCE3B-del. When the analysis was stratified for serologic data, we observed association in anti-cyclic citrullinated peptide (anti-CCP)-positive patients (P = 0.012, OR 1.51 [95% CI 1.09-2.13]) but not in anti-CCP-negative patients. CONCLUSION: We have identified an association between the LCE3C_LCE3B-del and RA, and we have verified a pleiotropic effect of a common genetic risk factor (LCE3C_LCE3B-del) for autoimmune diseases that is involved in both psoriasis and RA.
20360783 Podiatry services for patients with arthritis: an unmet need. 2010 Mar 5 Foot problems are extremely common in patients with rheumatoid arthritis (RA). There is ample evidence that foot pain, either alone or as a comorbidity, contributes significantly to disability. Despite the high prevalence of foot disease in RA, this problem is often trivialised or underappreciated. The inequity in foot health provision for patients with rheumatic disorders in New Zealand has recently been highlighted. Expertise in dealing with foot problems is often limited among healthcare professionals, and it has been argued that better integration of podiatric services into rheumatology services would be beneficial. The aim of this paper is to highlight the major issues related to foot care for patients with arthritis and provide key recommendations that should implemented to improve access to podiatric services in New Zealand.
20371395 Monoclonal antibodies and fusion proteins and their complications: targeting B cells in au 2010 Apr The immune system consists of a complex array of immunocompetent cells and inflammatory mediators that exist in complex networks. These components interact through cascades and feedback circuits, maintaining physiologic inflammation and immunosurveillance. In various autoimmune conditions, a foreign or auto-antigen may upset this fine balance, leading to dysregulated immunity, persistent inflammation, and ultimately pathologic sequelae. In recent years, there has been tremendous progress delineating the specific components of the immune system that contribute to normal immunity and specific disease states. With this greater understanding of pathogenesis coupled with advances in biotechnology, many immunomodulatory agents, commonly called biologic agents, have been introduced. The 2 most common classes of biologic agents are monoclonal antibodies and fusion proteins. These agents can inhibit targets with exquisite specificity to optimize outcomes and minimize toxicity. B cells contribute significantly to the initiation and perpetuation of the immune responses. B cells not only can produce potentially pathologic autoantibodies and proinflammatory cytokines but also can present antigens to T cells and provide costimulatory signals essential for T-cell activation, clonal expansion, and effector function. This review focuses on biologic agents targeting B cells in the treatment of rheumatoid arthritis and systemic lupus erythematosus.
19473565 Assessment of disease activity in rheumatoid arthritis using a novel folate targeted radio 2009 Mar OBJECTIVES: Development of a simple and accurate technique for detecting active inflammation in the joints and other tissues of patients with inflammatory disorders is an unmet need in rheumatic diseases. This study is a preliminary assessment of the safety and usage of a radiopharmaceutical, FolateScan (Technetium-99m EC20; 99mTc-EC20), for detecting disease activity in patients with rheumatoid arthritis. METHODS: EC20 is a folate-targeted diagnostic radiopharmaceutical which binds to the folate receptor and is preferentially taken up by activated macrophages. In this open-label, cross-sectional study, a total of 40 patients with RA (26 with one or more swollen joints, 14 with clinically quiescent joint disease; 0/66 joint count) as well as 6 patients with osteoarthritis, 12 patients with other inflammatory conditions and 5 healthy subjects received 0.1 mg of EC20 labeled with 20-25mCi of technetium-99m. Disease activity was scored in each joint and other target tissues by a radiologist blinded to the clinical assessment, and results were compared to the rheumatologist's physical examination, which served as the test standard. RESULTS: The 40 patients (78% female) with RA had a mean age of 56.9 years. Assessment of uptake of 99mTc-EC20 in joints of patients with RA based on image analysis was compared to the clinical examination. FolateScan detected more actively involved joints in 27 patients (68%) than joints recorded as "swollen", and more actively involved joints in 25 patients (63%) than joints recorded as "painful and/or swollen". The number of swollen joints by clinical exam was correlated with ESR (r=0.43; p=0.006) and C-rp (r=0.35; p=0.03). The number of actively involved joints by FolateScan was also correlated with ESR (r=0.47; p=0.002) and C-rp (r=0.36; p=0.02). Joint uptake was also seen in patients with osteoarthritis. CONCLUSION: FolateScan is a potentially useful tool for detection of disease activity in patients with RA and may be more sensitive than the physical examination.
20516016 Relationship between rheumatoid factor isotypes and IgG anti-cyclic citrullinated peptide 2010 Aug 1 OBJECTIVE: To validate in a general patient population (GPP) the clinical value of measuring rheumatoid factor (RF) isotypes in relationship to IgG anti-cyclic citrullinated peptide (CCP) antibodies (CCP2 and CCP3). METHODS: Serum samples were obtained as follows: 1021 GPP, for whom RF was ordered for diagnosis, 137 with rheumatoid arthritis (RA), 100 healthy blood donors (HBD), and 50 with systemic lupus erythematosus. Turbidimetry and ELISA were utilized for RF screening, and individual RF isotypes and IgG anti-CCP antibodies were measured by ELISA; RF IgG was measured after pepsin digestion. RESULTS: We validated the generally accepted 90%-98% positive predictive value (PPV) and about 68% sensitivity of the anti-CCP2 test on our diagnosed cohorts as 96% (95% CI 89-99) and 65% (95% CI 56-73), respectively. The 282 RF IgM+ specimens identified in the GPP were subdivided into 3 subsets: (1) 83 as RF IgM+ IgG+ IgA+ with 63% (95% CI 51-73) anti-CCP2+ (i.e., sensitivity similar to the RA cohort); (2) 50 as RF IgM+ IgG- IgA+ with significantly fewer anti-CCP2+ (22%; 95% CI 12-36); and (3) about half as IgM+ IgG- IgA- with just 3% (95% CI 1-8) anti-CCP2+, i.e., not significantly different from the 1% (95% CI 0-5) in HBD. Thus, the chance for a specimen in the GPP to be anti-CCP2+ (i.e., to come from an RA patient) was increased by 7- and 21-fold, respectively, by identifying RF IgA and IgG in addition to IgM. About one-third of anti-CCP- RA patients in our cohort were RF IgM+ IgG+ IgA+, reflected as 3.4% in the anti-CCP2- GPP. The agreement between anti-CCP2 and anti-CCP3 was significantly higher for RF+ RA and GPP patients, 86% (95% CI 78-93) and 83% (95% CI 73-91), respectively, than for the RF- RA (27%; 95% CI 6-61), RF- GPP (4%; 95% CI 0-19), and non-RA controls. Anti-CCP2 but not anti-CCP3 significantly distinguished the HBD from the GPP (95% CI). CONCLUSION: Measurement of the 3 isotypes of RF may increase by 7- to 21-fold the chance of making the serologic diagnosis of RA; a testing algorithm is proposed. The anti-CCP antibody response appears significantly less peptide-specific in the presence of IgM RF than in its absence.
20564003 Adiponectin-mediated changes in effector cells involved in the pathophysiology of rheumato 2010 Oct OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased production of adipokines, which are cytokine-like mediators that are produced mainly in adipose tissue but also in synovial cells. Since RA synovial fibroblasts (RASFs), lymphocytes, endothelial cells, and chondrocytes are key players in the pathophysiology of RA, this study was undertaken to analyze the effects of the key adipokine adiponectin on proinflammatory and prodestructive synovial effector cells. METHODS: Lymphocytes were activated in part prior to stimulation. All cells were stimulated with adiponectin, and changes in gene and protein expression were determined by Affymetrix and protein arrays. Messenger RNA and protein levels were confirmed using semiquantitative reverse transcription-polymerase chain reaction (PCR), real-time PCR, and immunoassays. Intracellular signal transduction was evaluated using chemical signaling inhibitors. RESULTS: Adiponectin stimulation of human RASFs predominantly induced the secretion of chemokines, as well as proinflammatory cytokines, prostaglandin synthases, growth factors, and factors of bone metabolism and matrix remodeling. Lymphocytes, endothelial cells, and chondrocytes responded to adiponectin stimulation with enhanced synthesis of cytokines and various chemokines. Additionally, chondrocytes released increased amounts of matrix metalloproteinases. In RASFs, adiponectin-mediated effects were p38 MAPK and protein kinase C dependent. CONCLUSION: Our previous findings indicated that adiponectin was present in inflamed synovium, at sites of cartilage invasion, in lymphocyte infiltrates, and in perivascular areas. The findings of the present study indicate that adiponectin induces gene expression and protein synthesis in human RASFs, lymphocytes, endothelial cells, and chondrocytes, supporting the concept of adiponectin being involved in the pathophysiologic modulation of RA effector cells. Adiponectin promotes inflammation through cytokine synthesis, attraction of inflammatory cells to the synovium, and recruitment of prodestructive cells via chemokines, thus promoting matrix destruction at sites of cartilage invasion.
21113810 S1P-targeted therapy for elderly rheumatoid arthritis patients with osteoporosis. 2011 Jul Therapeutics targeting sphingosine-1-phosphate (S1P), a kind of lipid mediator regulating immune cell trafficking, has been emerging rapidly as a novel line of regimen for autoimmune diseases, including rheumatoid arthritis (RA). Here, we propose that S1P-targeted therapy is beneficial not only for limiting inflammation but for preventing bone-resorptive disorders, such as osteoporosis, by controlling the migratory behavior of osteoclast precursors and therefore would be good for treating elderly female RA patients who suffer from postmenopausal osteoporosis and arthritis simultaneously.
21128049 [Infectious complications of biologic therapy in patients with rheumatoid arthritis]. 2010 Dec The introduction of biological disease-modifying drugs (DMARDs) has substantially improved the treatment options for patients with rheumatoid arthritis. However, infectious complications represent the most common side effects of these drugs, including severe infections as well as rare opportunistic infections. Treating patients on biological DMARDs is therefore one of the biggest challenges in rheumatology care. The present review describes the current state of knowledge regarding frequency and type of infectious complications associated with biological DMARDs. The article focuses mainly on risk management, in particular on diagnosis and recurrence prevention of tuberculosis and reactivation of hepatitis B virus infection. Furthermore, we discuss the importance of vaccinations in primary disease prevention in patients with rheumatoid arthritis.
19019259 Exploring the relationship between cognition and self-reported pain in residents of homes 2009 Feb BACKGROUND: Pain poses a major problem in older adults, specifically for those living in homes for the elderly. Previous research indicates that the presence of pain may be associated with changes in cognitive functions. It is unclear, however, how the reported experience of pain relates to cognitive functioning in elderly people with chronic pain. The present study was intended to examine the relationship between clinical pain experience and neuropsychological status in residents of homes for the elderly. METHODS: Forty-one residents suffering from arthritis or arthrosis completed tests measuring memory, processing speed, and executive function. The sensory-discriminative and the affective-motivational aspects of clinical pain were measured. RESULTS: Performance on executive function tests was positively related to self-reported pain experience. No relationship was observed between pain and memory or processing speed performance. CONCLUSION: The present study shows that executive functioning is related to the severity of subjectively reported pain. Possible explanations for this association are discussed.
20200692 Golimumab: A novel anti-TNF-alpha human monoclonal antibody for rheumatoid arthritis, psor 2010 Jan Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, has been implicated in the pathology of a variety of chronic autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. The introduction of TNF-alpha inhibitors represented a significant advance in the management of these diseases but the responses of individual patients to TNF-alpha inhibitors are not homogeneous and more therapeutic tools are needed. Golimumab (CNTO-148) is a novel anti-TNF-alpha human monoclonal antibody that blocks both soluble and transmembrane TNF-alpha. It is indicated in the treatment of adults with moderately to severely active rheumatoid arthritis in combination with methotrexate, in adults with active and progressive psoriatic arthritis either alone or in combination with methotrexate, and in adult patients with active ankylosing spondylitis who have had an inadequate response to conventional therapies. Golimumab has generally been well tolerated in clinical trials with a safety profile comparable to other currently available TNF-alpha inhibitors. Its advantages are that it can be administered s.c. once monthly, it is labeled for patient self-administration and is suitable for both s.c. and i.v. administration. Golimumab is currently being investigated in other chronic inflammatory diseases.
20833178 A novel method for the detection of antibodies to adalimumab in the presence of drug revea 2010 Oct 31 Production of anti drug antibodies (ADA) in adalimumab treated RA patients is associated with reduced serum adalimumab levels and less clinical response. However, most current assays to measure ADA are unable to detect ADA in complex with adalimumab. Thus, ADA is only measured if antibody production exceeds drug levels in the serum, meaning that ADA formation is underestimated. The aim of this study is to develop a method to detect ADA in the presence of drug. A pH-shift-anti-idiotype Antigen binding test (PIA) was used to enable ADA measurement in the presence of adalimumab. ADA-adalimumab complexes were dissociated by acid treatment and addition of excess rabbit anti-idiotype-F(ab) before neutralization. Rabbit anti-idiotype-F(ab) blocks reformation of ADA-drug complexes by competing with patient ADA for adalimumab binding. Released ADA are measured by an antigen binding test (ABT). The PIA enabled detection of ADA in the presence of large excess of adalimumab and was used to measure ADA in 30 adalimumab treated rheumatoid arthritis (RA) patients during the first 28 weeks of treatment. It revealed ADA in 21 out of 30 tested patients, while the ABT detected ADA in only 5 patients. Indicating that an immunogenic reaction towards adalimumab is present in the majority of adalimumab treated patients.
19822088 Role of the netrin system of repellent factors on synovial fibroblasts in rheumatoid arthr 2009 Jul Changes in the expression of repellent factors, i.e., Netrins and their receptors, may be responsible for the invasive behavior of the synovial tissue cells in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). This study was carried out to analyze the expression of Netrins and their receptors in synovial cells of patients with RA, OA, and control subjects without synovial inflammation. Quantitative RT-PCR was performed to measure the expression of Netrin-1, -3, -4, Neogenin, DCC, UNC5A-D. The influence of Netrin-1 on synovial fibroblasts (SF) was analyzed by determining proliferation, migration, and their ability to organize collagen. SF expressed all repellent factors of the Netrin family. When comparing SF of healthy donors to patients with RA and OA, a stronger expression of UNC5B (4 fold) and UNC5C (769 fold) in RA and OA was found, whereas expression of the other molecules revealed no significant differences. Treating the SF-cells with recombinant Netrin-1 resulted in inhibition of migration of RA- and OA-SFs whereas control cells were not affected. The stronger expression of UNC5B and UNC5C receptors might contribute to the disordered phenotype of RA- and OA-SFs. Addition of Netrin-1 reduces the migratory ability of SFs, potentially by repulsion, as seen in neuronal cells in embryonic development. Due to its function, Netrin-1 may constitute a novel target in the treatment of OA and RA.