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Sample records for monoclonal rheumatoid factor

  1. Rheumatoid factor interference in immunogenicity assays for human monoclonal antibody therapeutics.

    Science.gov (United States)

    Tatarewicz, Suzanna; Miller, Jill M; Swanson, Steven J; Moxness, Michael S

    2010-05-31

    Rheumatoid factors (RFs) are endogenous human antibodies that bind to human gamma globulins. RFs demonstrate preferential binding to aggregated gamma globulins and are involved in the clearing mechanism of immune complexes. Immunoassays designed to measure human anti-human antibodies (HAHA) after administration of monoclonal antibody therapeutics are thus vulnerable to interference from RFs. When using a sensitive electrochemiluminescent (ECL) bridging immunoassay, samples from subjects with rheumatoid arthritis demonstrated much higher baseline reactivity than healthy subjects. Interference was found to be dependent on the aggregation state of the therapeutic antibody that had been conjugated with the detection reagent (ruthenium). Size exclusion high performance liquid chromatography (SE-HPLC) demonstrated that of the total integrated peaks, as little as 0.55% high molecular weight aggregates (>600kDa) were sufficient to cause increased reactivity. Stability studies of the ruthenium and biotin conjugated therapeutic antibody indicated that storage time, temperature and buffer formulation were critical in maintaining the integrity of the reagents. Through careful SE-HPLC monitoring we were able to choose appropriate storage and buffer conditions which led to a reduction in the false reactivity rate in therapeutic-naïve serum from a rheumatoid arthritis population.

  2. Monoclonal antibodies in rheumatoid arthritis: comparative effectiveness of tocilizumab with tumor necrosis factor inhibitors

    Directory of Open Access Journals (Sweden)

    Tanaka T

    2014-04-01

    Full Text Available Toshio Tanaka,1,2 Yoshihiro Hishitani,3 Atsushi Ogata2,3 1Department of Clinical Application of Biologics, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan; 2Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan; 3Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan Abstract: Rheumatoid arthritis (RA is a chronic inflammatory disease characterized by persistent joint inflammation, systemic inflammation, and immunological abnormalities. Because cytokines such as tumor necrosis factor (TNF-α and interleukin (IL-6 play a major role in the development of RA, their targeting could constitute a reasonable novel therapeutic strategy for treating RA. Indeed, worldwide clinical trials of TNF inhibiting biologic disease modifying antirheumatic drugs (bDMARDs including infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept as well as the humanized anti-human IL-6 receptor antibody, tocilizumab, have demonstrated outstanding clinical efficacy and tolerable safety profiles, resulting in worldwide approval for using these bDMARDs to treat moderate to severe active RA in patients with an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARDs. Although bDMARDs have elicited to a paradigm shift in the treatment of RA due to the prominent efficacy that had not been previously achieved by sDMARDs, a substantial percentage of patients failed primary or secondary responses to bDMARD therapy. Because RA is a heterogeneous disease in which TNF-α and IL-6 play overlapping but distinct pathological roles, further studies are required to determine the best use of TNF inhibitors and tocilizumab in individual RA patients. Keywords: interleukin-6, rheumatoid arthritis, adalimumab, biologic

  3. MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis

    DEFF Research Database (Denmark)

    Behrens, Frank; Tak, Paul P; Ostergaard, Mikkel

    2015-01-01

    OBJECTIVES: To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). METHODS: Patients with active, moderate RA were enrolled in a randomised...... placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified...... with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases. TRIAL REGISTRATION NUMBER: NCT01023256....

  4. Elevated rheumatoid factor and long term risk of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Schnohr, Peter

    2012-01-01

    To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis.......To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis....

  5. Rheumatoid factor (RF)

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003548.htm Rheumatoid factor (RF) To use the sharing features on this ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  6. Determination of IgE rheumatoid factor

    International Nuclear Information System (INIS)

    Herrmann, D.; Schlenvoigt, G.; Jaeger, L.

    1987-01-01

    A solid-phase radioimmunoassay and an enzyme-linked immunosorbent assay have been developed for the identification of IgE rheumatoid factor (IgE RF). For both, human IgG was used as antigen. Bound IgE RF was detected by means of commercially available rabbit anti-human IgE antiserum and 125 I-labelled sheep anti-rabbit IgG as well as monoclonal anti-human-ε-chain antibody and horse-radish peroxidase-labelled sheep anti-mouse IgG. The presence of IgM RF did not cause false positive results. Correlation in the results of both assays were significant, the reproducibility was very good. In 50.6% of 79 sera from patients with rheumatoid arthritis IgE RF has been detected with both or one of the methods. Only in 1 out of 12 seronegative rheumatoid arthritis sera IgE RF was identified. (author)

  7. Recombinant human monoclonal autoantibodies specific for citrulline-containing peptides from phage display libraries derived from patients with rheumatoid arthritis.

    NARCIS (Netherlands)

    Raats, J.M.H.; Wijnen, E.M.; Pruijn, G.J.M.; Hoogen, F.H.J. van den; Venrooij, W.J.W. van

    2003-01-01

    OBJECTIVE: To isolate and characterize monoclonal autoantibodies (Mab) directed to citrullinated antigens from patients with rheumatoid arthritis (RA). METHODS: Using lymphocytes from bone marrow or peripheral blood from RA patients, we constructed antibody fragment libraries representing the

  8. Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

    Energy Technology Data Exchange (ETDEWEB)

    Malviya, G.; Dierckx, R.A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Conti, F. [Rheumatology Unit, I Faculty of Medicine and Surgery, Sapienza University of Rome (Italy); Chianelli, M. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Unit of Nuclear Medicine, Regina apostolorum Hospital, Albano, Rome (Italy); Scopinaro, F. [Nuclear Medicine Department, Sapienza University of Rome, St. Andrea Hospital, Rome (Italy); Signore, A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Nuclear Medicine Department, Sapienza University of Rome, St. Andrea Hospital, Rome (Italy)

    2010-02-15

    The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-{alpha}, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with {sup 99m}Tc or {sup 111}In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform 'evidence-based biological therapy' of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for

  9. Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

    International Nuclear Information System (INIS)

    Malviya, G.; Dierckx, R.A.; Conti, F.; Chianelli, M.; Scopinaro, F.; Signore, A.

    2010-01-01

    The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-α, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with 99m Tc or 111 In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform 'evidence-based biological therapy' of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for therapy decision-making and

  10. Rheumatoid disease without arthritis; clinical case of pulmonary fibrosis, rheumatoid nodulosis and positive rheumatoid factor without arthritis

    International Nuclear Information System (INIS)

    Ochoa Franco, Julian Andres; Canas Davila, Carlos Alberto

    2003-01-01

    We reported a case of a patient suffering pulmonary fibrosis rapidly progressive and a positive rheumatoid factor test with the presence of HLA DR11 y HLADR17, without arthritis, We discuss how rare is this clinical appearance, and remark the concept that rheumatoid arthritis is a systemic disease, with a wide clinical presentation, that some authors with a right criteria have called rheumatoid disease

  11. MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial

    Science.gov (United States)

    Behrens, Frank; Tak, Paul P; Østergaard, Mikkel; Stoilov, Rumen; Wiland, Piotr; Huizinga, Thomas W; Berenfus, Vadym Y; Vladeva, Stoyanka; Rech, Juergen; Rubbert-Roth, Andrea; Korkosz, Mariusz; Rekalov, Dmitriy; Zupanets, Igor A; Ejbjerg, Bo J; Geiseler, Jens; Fresenius, Julia; Korolkiewicz, Roman P; Schottelius, Arndt J; Burkhardt, Harald

    2015-01-01

    Objectives To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte–macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). Methods Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety. Results Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters. Conclusions MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases. Trial registration number NCT01023256 PMID:24534756

  12. MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial.

    Science.gov (United States)

    Behrens, Frank; Tak, Paul P; Østergaard, Mikkel; Stoilov, Rumen; Wiland, Piotr; Huizinga, Thomas W; Berenfus, Vadym Y; Vladeva, Stoyanka; Rech, Juergen; Rubbert-Roth, Andrea; Korkosz, Mariusz; Rekalov, Dmitriy; Zupanets, Igor A; Ejbjerg, Bo J; Geiseler, Jens; Fresenius, Julia; Korolkiewicz, Roman P; Schottelius, Arndt J; Burkhardt, Harald

    2015-06-01

    To determine the safety, tolerability and signs of efficacy of MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF), in patients with rheumatoid arthritis (RA). Patients with active, moderate RA were enrolled in a randomised, multicentre, double-blind, placebo-controlled, dose-escalation trial of intravenous MOR103 (0.3, 1.0 or 1.5 mg/kg) once a week for 4 weeks, with follow-up to 16 weeks. The primary outcome was safety. Of the 96 randomised and treated subjects, 85 completed the trial (n=27, 24, 22 and 23 for pooled placebo and MOR103 0.3, 1.0 and 1.5 mg/kg, respectively). Treatment emergent adverse events (AEs) in the MOR103 groups were mild or moderate in intensity and generally reported at frequencies similar to those in the placebo group. The most common AE was nasopharyngitis. In two cases, AEs were classified as serious because of hospitalisation: paronychia in a placebo subject and pleurisy in a MOR103 0.3 mg/kg subject. Both patients recovered fully. In exploratory efficacy analyses, subjects in the MOR103 1.0 and 1.5 mg/kg groups showed significant improvements in Disease Activity Score-28 scores and joint counts and significantly higher European League Against Rheumatism response rates than subjects receiving placebo. MOR103 1.0 mg/kg was associated with the largest reductions in disease activity parameters. MOR103 was well tolerated and showed preliminary evidence of efficacy in patients with active RA. The data support further investigation of this monoclonal antibody to GM-CSF in RA patients and potentially in those with other immune-mediated inflammatory diseases. NCT01023256. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Immunohistochemical Analysis of Inflammatory Rheumatoid Synovial Tissues Using Anti-Human Podoplanin Monoclonal Antibody Panel.

    Science.gov (United States)

    Suzuki, Tomoto; Takakubo, Yuya; Oki, Hiroharu; Liu, Xing; Honma, Ryusuke; Naganuma, Yasushi; Goodman, Stuart B; Kaneko, Mika K; Kato, Yukinari; Takagi, Michiaki

    2018-02-01

    Podoplanin (PDPN) is a transmembrane sialoglycoprotein, which is expressed in several normal tissues and malignant tumors. Although PDPN expression in rheumatoid arthritis (RA) has been reported, the role of PDPN in RA and other arthritic conditions has not been fully elucidated. In this study, we examined PDPN expression in inflammatory synovial tissues using an anti-human PDPN (hPDPN) monoclonal antibody (mAb) panel to select the most useful one for evaluation of synovitis. Synovial tissue samples were obtained from 11 RA patients and 9 osteoarthritis (OA) patients undergoing joint surgery. PDPN-positive cells were immunostained by a panel of PDPN mAbs (NZ-1, LpMab-3, LpMab-7, LpMab-10, LpMab-12, LpMab-13, and LpMab-17), followed by cell grading of inflammation and cell counting of PDPN-positivity by a quantitative analyzer. Immunohistochemistry showed that PDPN was markedly expressed in both macrophage-like type A and fibroblast-like type B lining cells of the hyperplastic synovial lining cell layer, and macrophages and fibroblasts in the stroma of RA. Among anti-PDPN mAbs, LpMab-12 showed the highest score. In inflammatory OA synovium, PDPN expression was also detectable. Although LpMab-12 also showed the highest score in OA, the difference was not statistically significant. The inflammatory synovitis score of RA was significantly higher than that of OA. PDPN was expressed in inflammatory lining cells and sublining stroma of RA and OA synovium. In the seven anti-hPDPN antibodies examined, LpMab-12 was the most stainable antibody for PDPN in RA synovitis. Thus, LpMab-12 for PDPN has a possible and promising specific biomarker for evaluating synovitis in RA and inflammatory OA.

  14. Blood cell gene expression profiling in rheumatoid arthritis. Discriminative genes and effect of rheumatoid factor

    DEFF Research Database (Denmark)

    Bovin, Lone Frier; Rieneck, Klaus; Workman, Christopher

    2004-01-01

    To study the pathogenic importance of the rheumatoid factor (RF) in rheumatoid arthritis (RA) and to identify genes differentially expressed in patients and healthy individuals, total RNA was isolated from peripheral blood mononuclear cells (PBMC) from eight RF-positive and six RF-negative RA...... patients, and seven healthy controls. Gene expression of about 10,000 genes were examined using oligonucleotide-based DNA chip microarrays. The analyses showed no significant differences in PBMC expression patterns from RF-positive and RF-negative patients. However, comparisons of gene expression patterns...

  15. Negative interference by rheumatoid factor in alpha-fetoprotein chemiluminescent microparticle immunoassay.

    Science.gov (United States)

    Wang, Hui; Bi, Xiaohui; Xu, Lei; Li, Yirong

    2017-01-01

    Background Rheumatoid factor causes positive interference in multiple immunoassays. Recently, negative interference has also been found in immunoassays in the presence of rheumatoid factor. The chemiluminescent microparticle immunoassay is widely used to determine serum alpha-fetoprotein. However, it is not clear whether the presence of rheumatoid factor in the serum causes interference in the chemiluminescent microparticle immunoassay of alpha-fetoprotein. Methods Serum alpha-fetoprotein was determined using the ARCHITECT alpha-fetoprotein assay. The estimation of alpha-fetoprotein recovery was carried out in samples prepared by diluting high-concentration alpha-fetoprotein serum with rheumatoid factor-positive or rheumatoid factor-negative serum. Paramagnetic microparticles coated with hepatitis B surface antigen-anti-HBs complexes were used to remove rheumatoid factor from the serum. Results The average recovery of alpha-fetoprotein was 88.4% and 93.8% in the rheumatoid factor-positive and rheumatoid factor-negative serum samples, respectively. The recovery of alpha-fetoprotein was significantly lower in the rheumatoid factor-positive serum samples than in the rheumatoid factor-negative serum samples. In two of five rheumatoid factor-positive samples, a large difference was found (9.8%) between the average alpha-fetoprotein recoveries in the serially diluted and initial recoveries. Fourteen rheumatoid factor-positive serum samples were pretreated with hepatitis B surface antigen-anti-HBs complex-coated paramagnetic microparticles. The alpha-fetoprotein concentrations measured in the pretreated samples increased significantly. Conclusions It was concluded that the alpha-fetoprotein chemiluminescent microparticle immunoassay is susceptible to interference by rheumatoid factor, leading to significantly lower results. Eliminating the incidence of negative interference from rheumatoid factor should be an important goal for immunoassay providers. In the meantime

  16. Tissue factor expression in rheumatoid synovium: a potential role in pannus invasion of rheumatoid arthritis.

    Science.gov (United States)

    Chen, Lujun; Lu, Yahua; Chu, Yang; Xie, Jun; Ding, Wen'ge; Wang, Fengming

    2013-09-01

    Angiogenesis, as well as pannus formation within the joint, plays an important role in the erosion of articular cartilage and bone in the pathological process of rheumatoid arthritis (RA). Tissue factor (TF), an essential initiator of the extrinsic pathway of blood coagulation, is also involved in the angiogenesis and the pannus formation of RA progression. In the present study, we used immunofluorescence and confocal scanning methods to characterize TF immunolocalization in RA synovium. We showed that positive staining of TF could be immunolocalized in synoviocytes, CD19(+) B cells and CD68(+) macrophages, whereas weak or negative staining of tissue factor could be found in CD34(+) endothelial cells of neo-vessels, CD3(+) T cells and CD14(+) monocytes in RA synovium tissues. Our study demonstrates a detailed local expression of TF in the rheumatoid synovium, and supports the notion that TF, expressed not only by the synoviocytes themselves, but also the infiltrating CD19(+) B cells and CD68(+) macrophages, is involved in the pannus invasion in the progression of rheumatoid arthritis. Copyright © 2013 Elsevier GmbH. All rights reserved.

  17. Structural features of Fab fragments of rheumatoid factor IgM-RF in solution

    International Nuclear Information System (INIS)

    Volkov, V. V.; Lapuk, V. A.; Shtykova, E. V.; Stepina, N. D.; Dembo, K. A.; Sokolova, A. V.; Amarantov, S. V.; Timofeev, V. P.; Ziganshin, R. Kh.; Varlamova, E. Yu.

    2008-01-01

    The structural features of the Fab fragments of monoclonal (Waldenstroem's disease) immunoglobulin M (IgM) and rheumatoid immunoglobulin M (IgM-RF) were studied by a complex of methods, including small-angle X-ray scattering (SAXS), electron spin resonance (ESR), and mass spectrometry (MS). The Fab-RF fragment was demonstrated to be much more flexible in the region of interdomain contacts, the molecular weights and the shapes of the Fab and Fab-RF macromolecules in solution being only slightly different. According to the ESR data, the rotational correlation time for a spin label introduced into the peptide sequence for Fab is twice as large as that for Fab-RF (21±2 and 11±1 ns, respectively), whereas the molecular weights of these fragments differ by only 0.5% (mass-spectrometric data), which correlates with the results of molecular-shape modeling by small-angle X-ray scattering. The conclusion about the higher flexibility of the Fab-RF fragment contributes to an understanding of the specificity of interactions between the rheumatoid factor and the antigens of the own organism.

  18. Lymphoid irradiation in intractable rheumatoid arthritis: effects on the production of immunoglobulins and rheumatoid factors

    International Nuclear Information System (INIS)

    Hanly, J.G.; Bresnihan, B.; Hassan, J.; Whelan, A.; Feighery, C.; Moriarty, M.

    1985-01-01

    Changes in the production of immunoglobulins and rheumatoid factors (RF's) were studied in 20 patients with intractable rheumatoid arthritis (RA) following total doses of 750 rad or 2,000 rad lymphoid irradiation. Over a 12 month follow up period there was no consistent change in absolute serum or synovial fluid levels, or in synovial membrane production of either total IgG, IgA or IgM, or the corresponding RF fractions. The in-vitro production of immunoglobulins and IgM RF by peripheral blood mononuclear cells was also unaltered, except for one patient who had a dramatic rise in IgM RF production. Over the same period there was a significant overall reduction in disease activity following both doses of radiotherapy. It is concluded that the clinical response which occurs following lymphoid irradiation is not due to a reduction in RF production. Furthermore, the production of RF's appears to be unaffected by the changes in T cell immunity which occur following lymphoid irradiation. (author)

  19. Factors associated with sustained remission in patients with rheumatoid arthritis.

    Science.gov (United States)

    Martire, María Victoria; Marino Claverie, Lucila; Duarte, Vanesa; Secco, Anastasia; Mammani, Marta

    2015-01-01

    To find out the factors that are associated with sustained remission measured by DAS28 and boolean ACR EULAR 2011 criteria at the time of diagnosis of rheumatoid arthritis. Medical records of patients with rheumatoid arthritis in sustained remission according to DAS28 were reviewed. They were compared with patients who did not achieved values of DAS28<2.6 in any visit during the first 3 years after diagnosis. We also evaluated if patients achieved the boolean ACR/EULAR criteria. Variables analyzed: sex, age, smoking, comorbidities, rheumatoid factor, anti-CCP, ESR, CRP, erosions, HAQ, DAS28, extra-articular manifestations, time to initiation of treatment, involvement of large joints, number of tender joints, number of swollen joints, pharmacological treatment. Forty five patients that achieved sustained remission were compared with 44 controls. The variables present at diagnosis that significantly were associated with remission by DAS28 were: lower values of DAS28, HAQ, ESR, NTJ, NSJ, negative CRP, absence of erosions, male sex and absence of involvement of large joints. Only 24.71% achieved the boolean criteria. The variables associated with sustained remission by these criteria were: lower values of DAS28, HAQ, ESR, number of tender joints and number of swollen joints, negative CRP and absence of erosions. The factors associated with sustained remission were the lower baseline disease activity, the low degree of functional disability and lower joint involvement. We consider it important to recognize these factors to optimize treatment. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  20. The future role of anti-tumour necrosis factor (TNF) products in the treatment of rheumatoid arthritis.

    Science.gov (United States)

    Camussi, G; Lupia, E

    1998-05-01

    Tumour necrosis factor-alpha (TNF alpha) is a pleiotropic cytokine which is overproduced in rheumatoid joints primarily by macrophages. This cytokine has a potential pathogenic role in the establishment of rheumatoid synovitis, in the formation of pannus tissue and in the process of joint destruction, as it increases synoviocyte proliferation and triggers a cascade of secondary mediators involved in the recruitment of inflammatory cells, in neo-angiogenesis and in the process of joint destruction. These findings made TNF alpha a potential target for anticytokine therapy. Experimental studies have shown that TNF alpha blockade by monoclonal antibodies or by soluble TNF receptor reduced the extent and severity of arthritis both in collagen-induced arthritis in mice and in transgenic mice overexpressing TNF alpha, which develop a rheumatoid-like destructive arthritis. Clinical studies based on the use of anti-TNF alpha antibodies or soluble receptors have suggested a potential beneficial effect of TNF alpha-blocking therapy in inducing amelioration of inflammatory parameters in patients with long-standing active disease. In these patients anti-TNF alpha therapy induces a rapid improvement in multiple clinical assessment of disease activity, including morning stiffness, pain score, Ritchie articular index and swollen joint count. The clinical benefits are associated with an improvement in some serological parameters, such as C-reactive protein and serum amyloid-A, erythrocyte sedimentation rate, blood cytokine levels, haemoglobin, white cells and platelet counts, rheumatoid factor titre and histological features of the synovium. However, it remains to be determined whether anti-TNF alpha therapy may be useful in the long term management of rheumatoid patients and in the achievement of better outcomes of disease. Because TNF alpha production also serves a specific function in host defence against infections and tumours, the adverse effects of long term anti-TNF alpha

  1. The anti-perinuclear factor (APF) and the rheumatoid factor (RF) in polymyalgia rheumatica and rheumatoid arthritis

    International Nuclear Information System (INIS)

    Nicholls, D.W.; Yee, R.; Harrison, A.A.

    2000-01-01

    Full text: Polymyalgia rheumatica (PMR) and rheumatoid arthritis (RA) are clinical diagnoses that may be difficult to differentiate in the elderly RA can present with a polymyatgic onset, and the manifestations of PMR include peripheral synovitis. HLA DR4 alleles are over-represented in both diseases The APF is a serum antibody against profilaggrins which is detected by binding to cytoplasmic granules in buccal mucosal cells It is found in a high percentage (78%) Of both seropositive and seronegative rheumatoid arthritis patients. We studied the APF in 17 patients with PMR (by Hunder criteria). 13 age and sex matched patients with RA (by ACR criteria) and 10 healthy controls, to see whether the presence of APF could help distinguish PMR from RA. APF was assayed using a standard buccal mucosal cell-based immunofluorescence technique Rheumatoid factor was measured by latex agglutination and by ELISA. 11/13 (85%) Of the RA patients were APF positive, of which 6/11 (55%) were strongly positive. 13/17 (76%) Of the PMR patients were positive but none of these were strongly positive Of the controls 2/10 (20%) were positive. APF had a sensitivity of 87% and specificity of 67% for PMR and a sensitivity of 85% and specificity of 80% for RA. The combination of an APF and an RA latex test resulted in a sensitivity of 82% and specificity of 0% for RA patients. We conclude that the presence of APF does not distinguish RA from PMR. This study provides additional evidence that RA and PMR are related diseases

  2. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Baslund, Bo; Rigby, William

    2010-01-01

    To investigate the safety and efficacy of ofatumumab, a novel human anti-CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to > or = 1 disease-modifying antirheumatic drug....

  3. The tumor necrosis factor-α inhibitor golimumab in the treatment of rheumatoid arthritis

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    Natalia Vladimirovna Chichasova

    2014-01-01

    Full Text Available The tumor necrosis factor-α (TNF-α golimumab (GLM, that is a fully human monoclonal anti-body, was registered in Russia in 2012 to treat rheumatic diseases, such as rheumatoid arthritis (RA, ankylosing spondylitis, and psoriatic arthritis. Its distinguishing characteristics are a high affinity for TNF-α and easiness-to-use: the drug as a 0.5-ml solution is injected subcutaneously once monthly. The registration of the medication was followed by the implementation of a massive program of clinical trials. The randomized placebo-controlled GO-FORWARD, GO-BEFORE, and GO-AFTER studies have indicated that GLM is effective in patients with RA from different subgroups and has a favorable safety profile as compared to that of the entire class of biological agents. According to the data of these studies, GLM had a positive effect on the functional status and quality of life in patients with RA: there was a significantly greater decrease in HAQ scores in both the early and long open treatment phases (to 5 years and in fatigability than in the control group (p=0.032, physical and mental health improvements, as shown by the SF-36 questionnaire, and a significant reduction in disability.

  4. Solid phase radioimmunoassay for quantitation of IgM rheumatoid factor (RF). Comparison with agglutination techniques and radioimmunoprecipitation polyethylene glycol assay (RIPEGA)

    Energy Technology Data Exchange (ETDEWEB)

    Herrmann, D.; Jaeger, L.; Hein, G.; Henzgen, M.; Fiebig, H.; Schlenvoigt, G.; Vogelsang, H. (Friedrich-Schiller-Universitaet, Jena (German Democratic Republic). Bereich Medizin; Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Biowissenschaften)

    1985-01-01

    A solid-phase radioimmunoassay capable of detecting nanogram quantities of human IgM rheumatoid factor using a monoclonal anti-..mu..-chain antibody is described. Human IgG did not interfere with the detection of IgM RF by this method. The small nonspecific binding of nonRF IgM to the human IgG coated tubes utilized in the assay must be corrected for by assaying samples in parallel bovine serum albumin coated control tubes only in cases of deviation of IgM from normal range. 69 coded and randomly arranged sera from patients with rheumatoid arthritis (RA), nonrheumatic joint diseases and healthy adult control subjects were investigated by this method, agglutination techniques as well as RIPEGA. A good correlation between solid-phase radioimmunoassay and agglutination techniques was found. Patients with seropositive RA had significantly higher concentrations of IgM RF than seronegative RA patients or control subjects.

  5. Cardiovascular risk factors in patients with rheumatoid arthritis in combination with hypertension depending on body weight

    Directory of Open Access Journals (Sweden)

    Sіrenko O.Yu.

    2014-11-01

    Full Text Available The objective was to evaluate the frequency of cardiovascular risk factors and hypertension in patients with rheumatoid arthritis depending on body weight. The study involved 100 patients with rheumatoid arthritis and stably selected therapy for more than 6 months at the age from 45 to 65 years (mean age 53,19 ± 5,40 years. Traditional cardiovascular risk was assessed, taking into account risk factors by SCORE scale and amended for patients with RA. The levels of total cholesterol, triglycerides, C-reactive protein, serum creatinine, body mass index, body area index were determined. Arterial hypertension was diagnosed in 41 (41% patients with rheuma¬toid arthritis and was associated with traditional risk factors (age, obesity, rheumatoid factor, hyperuricemia and the duration of glucocorticoid therapy. Obesity and excess body mass occurred in the majority of patients with rheumatoid arthritis, herewith the highest level of inflammation indicators and risk of cardiovascular events was in overweight patients. Obesity was associated with duration of rheumatoid arthritis, the activity of the inflammatory process, the duration of glucocorticoids taking. It is found that the traditional SCORE scale does not fully reflect the risk of cardiovascular events in rheumatoid arthritis. Identification of hypertension and obesity increases the information content of the risk assessment of cardiovascular events in rheumatoid arthritis.

  6. Elastolytic activity of human blood monocytes characterized by a new monoclonal antibody against human leucocyte elastase. Relationship to rheumatoid arthritis

    DEFF Research Database (Denmark)

    Jensen, H S; Christensen, L D

    1990-01-01

    The leucocyte elastase of human blood monocytes was investigated by applying a new monoclonal antibody which did not block the enzyme activity against elastin. In a fixed population of mononuclear cells (MNC) and using fluorescence activated cell sorting (FACS), the human leucocyte elastase (HLE...

  7. Radioimmunoassay of IgG and IgM rheumatoid factors reacting with human IgG

    International Nuclear Information System (INIS)

    Carson, D.A.; Lawrance, S.; Catalano, M.A.; Vaughan, J.H.; Abraham, G.

    1977-01-01

    Although IgG rheumatoid factor may play a central role in the pathogenesis of rheumatoid arthritis, previously there have been no precise methods for its specific measurement in serum and synovial fluid. This paper describes a solid phase radioimmunoassay for the independent quantification of IgM and IgG rheumatoid factor reacting with the Fc fragment of human IgG. As measured by this assay, serum IgG rheumatoid factor levels differed significantly between patients with seropositive and seronegative rheumatoid arthritis and normal control subjects. In addition, several sera and joint fluids from patients with seropositive rheumatoid arthritis, even without vasculitis, were shown by gel chromatography to have acid-dissociable complexes of IgG rheumatoid factor suggestive of IgG-IgG dimer or trimer formation

  8. The role of traditional cardiovascular risk factors among patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Brady, Sharmayne R E; de Courten, Barbora; Reid, Christopher M

    2009-01-01

    People with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD) compared with the general population. We investigated the relative contribution of traditional cardiovascular risk factors to this elevated risk.......People with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD) compared with the general population. We investigated the relative contribution of traditional cardiovascular risk factors to this elevated risk....

  9. Additional diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis.

    Science.gov (United States)

    Vallbracht, Inka; Helmke, Klaus

    2005-07-01

    In the past decade significant advantages have been made in the treatment of rheumatoid arthritis (RA) and therapeutic strategies have changed a lot. These days, highly effective disease modifying anti-rheumatic drugs enable intervention early in the disease process, in order to prevent major joint damage. For years, serological support in the diagnosis of RA has been limited to the presence of rheumatoid factors, although not very specific for RA. During the last years a variety of circulating non-RF antibodies have been discovered and reported to be of potential diagnostic value. CCP2 proved to be a very disease-specific and even sensitive marker for RA. In addition to the diagnostic properties, CCP showed to be a good prognostic marker, CCP helps to predict the erosive or nonerosive progression of the disease, and CCP is already present early in the disease. This diagnostic tool enables the clinician to choose the optimal therapeutic management for each single RA patient.

  10. CLINICAL-PATHOGENIC IMPORTANCE OF CORRELATION BETWEEN HISTOCHEMICAL INDICES OF BLOOD SYSTEM AND RHEUMATOID FACTOR IN PATIENTS WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    A B Zborovsky

    2001-01-01

    Full Text Available Summary Relation between rheumatoid factor (RF and levels of Myeloperoxidase (MPO, Na*-K +-A TPh- ase (ATPh-ase, 5'-Nucleotidase (5 ’-NT, Succinate dehydrogenase (SDG in cells of peripheral blood of rheumatoid arthritis (RA patients was investigated. 83 RA patients were observed. The activities of MPO, ATP-ase, 5’NT, SDG in blood cells were determined by hystochemical methods. In patients having increasing MPO activity in monocytes, normal level of SDG in lymphocytes and decreasing of 5'NT in monocytes and lymphocytes increasing of RF level was noted in 3 weeks after hystochemical changes (p<0.05. Determination of MPO in monocytes was the most informative test for forecasting of immunological changes in RA. The role of macrophage system in RA is discussed.

  11. Monoclonal antibodies to human factor VII: a one step immunoradiometric assay for VII:Ag.

    OpenAIRE

    Takase, T; Tuddenham, E G; Chand, S; Goodall, A H

    1988-01-01

    Three mouse monoclonal antibodies (RFF-VII/1, RFF-VII/2, and RFF-VII/3) which bind specifically to different epitopes on human factor VII antigen were raised. Two of the antibodies, RFF-VII/1 and RFF-VII/2, bound strongly to factor VII antigen (VII:Ag), but only RFF-VII/1 and RFF-VII/3 were potent inhibitors of factor VII coagulation activity (VII:C). RFF-VII/1 and RFF-VII/2 were used in a one step, double monoclonal immunoradiometric assay for VII:Ag. This was highly reproducible and detecte...

  12. Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

    Science.gov (United States)

    Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G

    1996-08-01

    The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

  13. Monoclonal antibodies to human factor VII: production of immunodepleted plasma for VII:C assays.

    OpenAIRE

    Takase, T; Tuddenham, E G; Chand, S; Goodall, A H

    1988-01-01

    A high affinity monoclonal antibody to factor VII (RFF-VII/1), coupled to sepharose, was used to immunodeplete factor VII from normal plasma. The plasma could be used as a substrate in a one stage coagulation assay and performed as well as, or better than, commercially available factor VII deficient plasma or plasma from congenitally deficient factor VII patients. Plasma from normal donors (n = 20), patients with liver disease (n = 20), and patients receiving warfarin (n = 20), or congenitall...

  14. New radioimmunoassay for IgM and IgG rheumatoid factors, based on a double antibody method

    Energy Technology Data Exchange (ETDEWEB)

    Nordfang, O. (Rigshospitalet, Copenhagen (Denmark)); Hoeier-Madsen, M.; Lieberkind, J. (Statens Seruminstitut, Copenhagen (Denmark)); Halberg, P. (Medical Department, Division of Rheumatology, Hvidovre Hospital, Hvidovre, Denmark)

    1981-11-30

    A new radioimmunoassay has been developed for measuring IgM and IgG rheumatoid factors. Diluted sera from donors and patients were incubated with immunoprecipitates prepared from sheep serum and rabbit anti-sheep IgG antiserum. The precipitates were washed, and radioiodinated rabbit F(ab')/sub 2/ fragments specific for human IgM or IgG were added. The precipitates were isolated by filtration and measured in a gamma counter. With this assay IgM rheumatoid factors were detected in sera from all patients with seropositive rheumatoid arthritis and in sera from 40% of patients with seronegative rheumatoid arthritis. IgG rheumatoid factors were found in sera from 68% of the seropositive and 40% of the seronegative patients. Gel filtration experiments demonstrated that it is possible to detect monomeric IgG rheumatoid factors and IgM rheumatoid factors of molecular weight smaller than pentameric IgM. Furthermore it has been shown that IgG rheumatoid factor activity is still present after reduction of IgM rheumatoid factors with dithiotreitol.

  15. Isotypes of Epstein-Barr Virus Antibodies in Rheumatoid Arthritis: Association with Rheumatoid Factors and Citrulline-Dependent Antibodies

    Directory of Open Access Journals (Sweden)

    Marie Wulff Westergaard

    2015-01-01

    Full Text Available In order to study the humoral immune response against Epstein-Barr virus (EBV in patients with rheumatoid arthritis (RA and to compare it with the two major autoantibody types in RA, plasma samples from 77 RA patients, 28 patients with systemic lupus erythematosus (SLE, and 28 healthy controls (HCs were investigated by enzyme-linked immunosorbent assays (ELISA. Increased percentages of positives and concentrations of IgG/IgA/IgM antibodies against the latent EBV nuclear antigen-1 (EBNA-1 were observed in RA patients compared to SLE patients and HCs. Increased concentrations and percentages of positives of IgG/IgA/IgM against the early lytic EBV antigen diffuse (EAD were also found in RA patients compared to HCs but were highest in SLE patients. Furthermore, associations between the elevated EBNA-1 IgA and EBNA-1 IgM levels and the presence of IgM and IgA rheumatoid factors (RFs and anti-citrullinated protein antibodies (ACPAs, IgG and between elevated IgA concentrations against EAD and the presence of RFs and ACPAs in RA patients were found. Thus, RA patients had elevated antibodies of all isotypes characteristic of latent EBV infection (whereas SLE patients had elevated antibodies characteristic of lytic EBV infection. Notably, for IgM and IgA (but not IgG, these were associated with the presence of characteristic RA autoantibodies.

  16. Does tocilizumab contribute to elevation of rheumatoid factor and induction of paradoxical syaloadenitis in rheumatoid arthritis patients?

    Science.gov (United States)

    Martinović Kaliterna, Dušanka; Aljinović, Jure; Perković, Dijana; Marasović Krstulović, Daniela; Marinović, Ivanka; Vlak, Tonko

    2014-02-01

    A 56-year-old woman, treated with tocilizumab (TCZ) for 8 months for severe rheumatoid arthritis (RA), was admitted to the hospital due to the swelling and tenderness of parotid glands. The patient was diagnosed with seropositive erosive RA in 1988, and treated with different disease modifying antirheumatic drugs (DMARDs) that were used together with a low dosage of glucocorticoides, followed by biologic therapy with infliximab and adalimumab which also proved to be inefficient. The patient had an excellent initial response on TCZ therapy. After 8 months, she was presented with an extreme enlargement of parotid glands. Bacterial, viral, and granulomatous diseases were excluded. A spectrum of autoantibodies including anti-Ro and anti-La showed normal values, expect for slightly elevated anti-cyclic citrullinated peptide (anti-CCP) and extreme elevation of the rheumatoid factor (RF) to 10,100 IU/ml. The biopsy of salivary glands was done and histological specimen showed limphoplasmocytic syaloadenitis. Tocilizumab therapy was stopped and the dosage of glucocorticoids and methotrexate (MTX) was raised. After 6 weeks, the patient was in better condition with slightly lower levels of RF (9,010 IU/ml). We hypothesise that in this patient, TCZ stimulated RF hyper production which can induce a paradoxical secondary syaloadenitis in RA.

  17. Periodontal and serum protein profiles in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitor adalimumab.

    Science.gov (United States)

    Kobayashi, Tetsuo; Yokoyama, Tomoko; Ito, Satoshi; Kobayashi, Daisuke; Yamagata, Akira; Okada, Moe; Oofusa, Ken; Narita, Ichiei; Murasawa, Akira; Nakazono, Kiyoshi; Yoshie, Hiromasa

    2014-11-01

    Tumor necrosis factor (TNF)-α inhibitor has been shown to affect the periodontal condition of patients with rheumatoid arthritis (RA). The aim of the present study is to assess the effect of a fully humanized anti-TNF-α monoclonal antibody, adalimumab (ADA), on the periodontal condition of patients with RA and to compare serum protein profiles before and after ADA therapy. The study participants consisted of 20 patients with RA treated with ADA. Clinical periodontal and rheumatologic parameters and serum cytokine levels were evaluated at baseline and 3 months later. Serum protein spot volume was examined with two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins with significant difference in abundance before and after ADA therapy were found and identified using mass spectrometry and protein databases. The patients showed a significant decrease in gingival index (P = 0.002), bleeding on probing (P = 0.003), probing depth (P = 0.002), disease activity score including 28 joints using C-reactive protein (P protein spots obtained, nine spots were significantly decreased in abundance at reassessment, corresponding to complement factor H, phospholipase D, serum amyloid A, complement component 4, and α-1-acid glycoprotein (P periodontal condition of patients with RA, which might be related to differences in serum protein profiles before and after ADA therapy.

  18. Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis

    NARCIS (Netherlands)

    Isaacs, John D.; Cohen, Stanley B.; Emery, Paul; Tak, Paul P.; Wang, Jianmei; Lei, Guiyuan; Williams, Sarah; Lal, Preeti; Read, Simon J.

    2013-01-01

    Studies examining the relationship between serological status (rheumatoid factor and/or anticitrullinated antibody) and rituximab treatment outcome in rheumatoid arthritis (RA) have been hampered by limited numbers of seronegative patients. To carry out a meta-analysis of trials from the rituximab

  19. Impact of Stopping Tumor Necrosis Factor-inhibitors on Rheumatoid Arthritis Patients' Burden of Disease

    NARCIS (Netherlands)

    Ghiti Moghadam, Marjan; ten Klooster, Peter M.; Vonkeman, Harald Erwin; Kneepkens, Eva L.; Klaasen, Ruth; Stolk, Jan N.; Tchetverikov, Ilja; Vreugdenhil, Simone A.; van Woerkom, Jan M.; Goekoop-Ruiterman, Yvonne P.M.; Landewé, Robert B.M.; van Riel, Piet L.C.M.; van de Laar, Mart A F J; Jansen, Tim L.

    2017-01-01

    OBJECTIVE: To determine the impact of stopping tumor necrosis factor inhibitor (TNFi) treatment on patient-reported outcomes (PROs) of physical and mental health status, health utility, pain, disability and fatigue in patients with established rheumatoid arthritis (RA). METHODS: In the pragmatic

  20. Impact of Stopping Tumor Necrosis Factor-inhibitors on Rheumatoid Arthritis Patients' Burden of Disease

    NARCIS (Netherlands)

    Ghiti Moghadam, Marjan; ten Klooster, Peter M.; Vonkeman, Harald E.; Kneepkens, Eva L.; Klaasen, Ruth; Stolk, Jan N.; Tchetverikov, Ilja; Vreugdenhil, Simone A.; van Woerkom, Jan M.; Goekoop-Ruiterman, Yvonne P. M.; Landewé, Robert B. M.; van Riel, Piet L. C. M.; van de Laar, Mart A. F. J.; Jansen, Tim L.

    2017-01-01

    To determine the impact of stopping tumor necrosis factor inhibitor (TNFi) treatment on patient-reported outcomes (PROs) of physical and mental health status, health utility, pain, disability and fatigue in patients with established rheumatoid arthritis (RA). In the pragmatic 12-month POET trial,

  1. Impact of Stopping Tumor Necrosis Factor inhibitors on Rheumatoid Arthritis Patients' Burden of Disease

    NARCIS (Netherlands)

    Ghiti Moghadam, Marjan; ten Klooster, Peter M.; Vonkeman, Harald Erwin; Kneepkens, Eva L.; Klaasen, Ruth; Stolk, Jan N.; Tchetverikov, Ilja; Vreugdenhil, Simone A.; van Woerkom, Jan M.; Goekoop-Ruiterman, Yvonne P.M.; Landewé, Robert B.M.; van Riel, Piet L.C.M.; van de Laar, Mart A F J; Jansen, Tim L.

    OBJECTIVE: To determine the impact of stopping tumor necrosis factor inhibitor (TNFi) treatment on patient-reported outcomes (PROs) of physical and mental health status, health utility, pain, disability and fatigue in patients with established rheumatoid arthritis (RA). METHODS: In the pragmatic

  2. Predictive factors of work disability in rheumatoid arthritis: a systematic literature review.

    NARCIS (Netherlands)

    Croon, de E.M.; Sluiter, J.K.; Nijssen, TF; Dijkmans, B.A.C.; Lankhorst, G.J.; Frings-Dresen, MH

    2004-01-01

    BACKGROUND: Work disability-a common outcome of rheumatoid arthritis (RA)-is a societal (for example, financial costs) and individual problem (for example, loss of status, income, social support, and distraction from pain and distress). Until now, factors that predict work disability in RA have not

  3. FUNCTIONAL DISABILITY IN EARLY RHEUMATOID-ARTHRITIS - DESCRIPTION AND RISK-FACTORS

    NARCIS (Netherlands)

    GUILLEMIN, F; SUURMEIJER, T; KROL, B; BOMBARDIER, C; BRIANCON, S; DOEGLAS, D; SANDERMAN, R; VANDENHEUVEL, W

    Objective. To provide a description and identify risk factors for functional disability in early rheumatoid arthritis (RA). Methods. A cohort of 337 patients with early RA with disease duration under 5 years was constituted in 2 areas in Fiance and The Netherlands. Examination included the Ritchie

  4. Heterophilic antibody interference affecting multiple hormone assays: Is it due to rheumatoid factor?

    Science.gov (United States)

    Mongolu, Shiva; Armston, Annie E; Mozley, Erin; Nasruddin, Azraai

    2016-01-01

    Assay interference with heterophilic antibodies has been well described in literature. Rheumatoid factor is known to cause similar interference leading to falsely elevated hormone levels when measured by immunometric methods like enzyme-linked immunosorbent assay (ELISA) or multiplex immunoasays (MIA). We report a case of a 60-year-old male patient with a history of rheumatoid arthritis referred to our endocrine clinic for investigation of hypogonadism and was found to have high serum levels of LH, FSH, SHBG, Prolactin, HCG and TSH. We suspected assay interference and further tests were performed. We used Heteroblock tubes and PEG precipitation to eliminate the interference and the hormone levels post treatment were in the normal range. We believe the interference was caused by high serum levels of rheumatoid factor. Although he was treated with thyroxine for 3 years, we believe he may have been treated inappropriately as his Free T4 level was always normal despite high TSH due to assay interference. Our case illustrates the phenomenon of heterophilic antibody interference likely due to high levels of rheumatoid factor. It is essential for clinicians and endocrinologists in particular to be aware of this possibility when making treatment decisions in these groups of patients.

  5. A high affinity monoclonal antibody recognizing the light chain of human coagulating factor VII.

    Science.gov (United States)

    Sarial, Sheila; Asadi, Farzad; Jeddi-Tehrani, Mahmood; Hadavi, Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Taghizadeh-Jahed, Masoud; Shokri, Fazel; Rabbani, Hodjattallah

    2012-12-01

    Factor VII (FVII) is a serine protease-coagulating element responsible for the initiation of an extrinsic pathway of clot formation. Here we generated and characterized a high affinity monoclonal antibody that specifically recognizes human FVII. Recombinant human FVII (rh-FVII) was used for the production of a monoclonal antibody using BALB/c mice. The specificity of the antibody was determined by Western blot using plasma samples from human, mouse, sheep, goat, bovine, rabbit, and rat. Furthermore, the antibody was used to detect transiently expressed rh-FVII in BHK21 cell line using Western blot and sandwich ELISA. A mouse IgG1 (kappa chain) monoclonal antibody clone 1F1-B11 was produced against rh-FVII. The affinity constant (K(aff)) of the antibody was calculated to be 6.4×10(10) M(-1). The antibody could specifically recognize an epitope on the light chain of hFVII, with no reactivity with factor VII from several other animals. In addition, transiently expressed rh-FVII in BHK21 cells was recognized by 1F1-B11. The high affinity as well as the specificity of 1F1-B11 for hFVII will facilitate the affinity purification of hFVII and also production of FVII deficient plasma and minimizes the risk of bovine FVII contamination when fetal bovine serum-supplemented media are used for production and subsequent purification of rh-FVII.

  6. Safety of Repeated Open-Label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Quattrocchi, Emilia; Ostergaard, Mikkel; Taylor, Peter C.

    2016-01-01

    Objectives To investigate the safety of ofatumumab retreatment in rheumatoid arthritis. Methods Patients with active rheumatoid arthritis participating in two phase III trials (OFA110635 and OFA110634) and a phase II extension trial (OFA111752) received individualised open-label ofatumumab retrea...

  7. Monoclonal anti-human factor VII antibodies. Detection in plasma of a second protein antigenically and genetically related to factor VII.

    OpenAIRE

    Broze, G J; Hickman, S; Miletich, J P

    1985-01-01

    Several murine monoclonal anti-human Factor VII antibodies were produced using hybridoma technology. Two noncompetitive monoclonal antibodies were used to examine by Western blotting the Factor VII cross-reactive material (CRM) in normal human plasma and three commercially available congenitally Factor VII-deficient plasmas, and to construct a facile "sandwich" immunoassay for plasma Factor VII. A second, previously undescribed, form of Factor VII CRM was detected in human plasma, which on We...

  8. Influence of tumor necrosis factor α in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    von der Schulenburg, Johann-Matthias

    2005-12-01

    Full Text Available Objective: Rheumatoid arthritis (RA is the most prevalent inflammatory rheumatic disorder. It is a chronic and incurable disease that leads to painful inflammation, often irreversible joint damage, and eventually to functional loss. Conventional treatment is based on unspecific immunosuppressive agents, e.g. Methotrexate, Azathioprin or Gold. However, the longterm outcomes of these approaches have been poor with frequently ongoing inflammatory disease activity, functional decline, and temporary or permanent work disability. More recently, antagonists of the human cytokine Tumor Necrosis Factor α (TNF-α have been introduced that are potent suppressors of inflammatory processes. Infliximab is a chimeric antibody against TNF-α. Etanercept is a soluble human TNF-α receptor. The report assesses the efficacy of TNF-α-antagonists to down-regulate inflammation, improve functional status and prevent joint damage in RA with particular regard to the following indications: Treatment of severe, refractory and ongoing disease activity despite adequate use of conventional antirheumatic agents; and treatment of early RA before conventional treatment failure has been demonstrated. Methods: A systematic review of the literature is been performed using established electronic databases. The literature search is supplemented by a hand search of journals and publications relevant to RA, reviews of websites of national and international rheumatologic expert societies, as well as contacts to manufacturers. A priori defined inclusion and exclusion criteria are used for literature selection. Analysis and evaluation of included publications are based on standardised criteria sets and checklists of the German Scientific Working Group for Technology Assessment in Health Care. Results: Health Technology Assessment reports and metaanalyses cannot be identified. A total of 12 clinical trials are analysed, as well as national and international expert recommendations and

  9. Chinese Registry of rheumatoid arthritis (CREDIT): II. prevalence and risk factors of major comorbidities in Chinese patients with rheumatoid arthritis.

    Science.gov (United States)

    Jin, Shangyi; Li, Mengtao; Fang, Yongfei; Li, Qin; Liu, Ju; Duan, Xinwang; Liu, Yi; Wu, Rui; Shi, Xiaofei; Wang, Yongfu; Jiang, Zhenyu; Wang, Yanhong; Yu, Chen; Wang, Qian; Tian, Xinping; Zhao, Yan; Zeng, Xiaofeng

    2017-11-15

    Rheumatoid arthritis patients are at higher risk of developing comorbidities. The main objective of this study was to evaluate the prevalence of major comorbidities in Chinese rheumatoid arthritis patients. We also aimed to identify factors associated with these comorbidities. Baseline demographic, clinical characteristics and comorbidity data from RA patients enrolled in the Chinese Registry of rhEumatoiD arthrITis (CREDIT) from Nov 2016 to August 2017 were presented and compared with those from five other registries across the world. Possible factors related to three major comorbidities (cardiovascular disease, fragility fracture and malignancy) were identified using multivariate logistic regression analyses. A total of 13,210 RA patients were included (80.6% female, mean age 52.9 years and median RA duration 4.0 years). Baseline prevalence rates of major comorbidities were calculated: CVD, 2.2% (95% CI 2.0-2.5%); fragility fracture, 1.7% (95% CI 1.5-1.9%); malignancy, 0.6% (95% CI 0.5-0.7%); overall major comorbidities, 4.2% (95% CI 3.9-4.6%). Advanced age was associated with all comorbidities. Male gender and disease duration were positively related to CVD. Female sex and longer disease duration were potential risk factors for fragility fractures. Ever use of methotrexate (MTX) was negatively related to baseline comorbidities. Patients with rheumatoid arthritis in China have similar prevalence of comorbidities with other Asian countries. Advanced age and long disease duration are possible risk factors for comorbidities. On the contrary, MTX may protect RA patients from several major comorbidities, supporting its central role in the management of rheumatoid arthritis.

  10. Prevalence of ischemic heart disease and associated factors in patients with rheumatoid arthritis in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Rafael Kmiliauskis Santos Gomes

    Full Text Available Abstract Objective: To estimate the prevalence of ischemic heart disease and associated factors in patients with rheumatoid arthritis. Methods: A cross-sectional study using the American College of Rheumatology diagnostic criteria in order to select patients seen at primary or secondary health care units in Blumenau, Santa Catarina, Southern Brazil, in 2014. The presence of ischemic heart disease was defined as an acute myocardial infarction with percutaneous coronary intervention or coronary artery bypass graft surgery that has occurred after diagnosis. Fischer's exact test, Wald's linear trend test, and multivariate logistic regression analysis were used to test the associations. Results: Among 296 patients (83.1% female with a mean age of 56.6 years and a mean rheumatoid arthritis duration of 11.3 years, 13 reported having acute myocardial infarction requiring a percutaneous or surgical reperfusion procedure, a prevalence of 4.4% (95% CI 2.0-6.7. Diabetes Mellitus (odds ratio [OR] 4.9 [95% CI 1.6-13.8] and disease duration >10 years (OR 8.2 [95% CI 1.8-39.7] were the only factors associated with an ischemic disease that remained in the final model, after the multivariate analysis. Conclusion: The prevalence of acute myocardial infarction was similar to that observed in other studies. Among the traditional risk factors, Diabetes Mellitus, and among the factors related to rheumatoid arthritis, disease duration, were the variables associated with comorbidity.

  11. Endogenous endophthalmitis in a rheumatoid patient on tumor necrosis factor alpha blocker

    Directory of Open Access Journals (Sweden)

    Agarwal Pankaj

    2007-01-01

    Full Text Available The development of anti-tumor necrosis factor (TNF therapies is a milestone in the therapy of rheumatic diseases. It is of concern whether all potential undesired complications of therapy have been evaluated within clinical trials which have led to treatment approval. Specialists prescribing TNF blockers should be aware of the unusual and severe complications that can occur. We describe a case of endogenous endophthalmitis in a rheumatoid patient on TNF alpha blocker.

  12. Health-related quality of life of patients with rheumatoid arthritis. Which factors are of significance?

    DEFF Research Database (Denmark)

    Linde, L.; Sørensen, J.; Ostergaard, M.

    2008-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease causing joint pain, loss of function and decreased health-related quality of life (HRQoL). HRQoL in RA patients is associated with several risk factors; in this paper the evidence relating to the most important risk factors is reviewed....... Modern medical therapy has improved HRQoL in RA patients, while demographic factors (female sex and older age), low socioeconomic status (in terms of education and position in the work force) and the presence of comorbid conditions appear to be associated with poorer HRQoL Udgivelsesdato: 2008/3/3...

  13. Shared epitope alleles remain a risk factor for anti-citrullinated proteins antibody (ACPA--positive rheumatoid arthritis in three Asian ethnic groups.

    Directory of Open Access Journals (Sweden)

    Too Chun-Lai

    Full Text Available BACKGROUND: To investigate the associations between HLA-DRB1 shared epitope (SE alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia. METHODS: 1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping. RESULTS: The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups. CONCLUSION: The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.

  14. Chimeric monoclonal antibody to tumor necrosis factor alpha (infliximab in psoriasis

    Directory of Open Access Journals (Sweden)

    Sridhar J

    2006-01-01

    Full Text Available Background: Insights into the pathogenesis of psoriasis have provided opportunities to target key steps in the disease process. Tumor necrosis factor-alpha (TNF-a being crucial to the pathogenesis of psoriasis, monoclonal antibodies against this cytokine have proved useful in its treatment. Aim: To study the efficacy of chimeric monoclonal antibody to TNF-a (infliximab in Indian patients with recalcitrant psoriasis vulgaris. Materials and Methods: Three patients with recalcitrant psoriasis vulgaris were studied. Baseline haemogram, biochemical parameters, chest radiograph and Mantoux skin test were performed. A loading dose regimen of 5 mg/kg infliximab was administered at weeks 0, 2 and 6. PASI assessment, adverse drug event monitoring and laboratory assessments were carried out at 2-week intervals until week 10. Patients were followed up until week 22 for relapse. Results: Infliximab was well tolerated. The mean PASI was 25.4 at presentation and declined to 5.5 at 10 weeks. PASI 75 was attained at a mean of 9.6 weeks. Relapse occurred at a mean of 18.6 weeks after the first infusion. Conclusions: This study on Indian patients brings out the importance of cytokine-based therapies in psoriasis. Indigenous production could make these therapies a viable therapeutic option for psoriasis patients in the near future.

  15. Higher serum levels of rheumatoid factor and anti-nuclear antibodies in helicobacter pylori-infected peptic ulcer patients.

    Science.gov (United States)

    Jafarzadeh, Abdollah; Nemati, Maryam; Rezayati, Mohammad Taghi; Nabizadeh, Mansooreh; Ebrahimi, Medhi

    2013-07-01

    H. pylori infection has been associated with some autoimmune disorders. The aim of this study was to evaluate the serum concentrations of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected peptic ulcer patients, H. pylori-infected asymptomatic carriers and a healthy control group. A Total of 100 H. pylori-infected peptic ulcer patients, 65 asymptomatic carriers and 30 healthy H. pylori-negative subjects (as a control group) were enrolled into study. Serum samples of participants tested for the levels of rheumatoid factor and anti-nuclear antibodies by use of ELISA. The mean serum levels of rheumatoid factor and anti-nuclear antibodies in peptic ulcer group was significantly higher in comparison to the control group (ppeptic ulcer patients and asymptomatic carriers groups regarding the mean serum levels of rheumatoid factor and anti-nuclear antibodies. The mean serum levels of rheumatoid factor in men with peptic ulcer was significantly higher compared to the group of healthy men (ppeptic ulcer patients or asymptomatic carriers groups, the mean serum levels of rheumatoid factor was higher than that in healthy women, but the differences were not statistically significant. Also, no significant differences were observed between men and women with peptic ulcer, asymptomatic carriers control groups based on the serum levels of anti-nuclear antibodies. The results showed higher serum levels of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected patients with peptic ulcer disease which represent the H. pylori-related immune disturbance in these patients. Additional follow-up studies are necessary to clarify the clinical significance of these autoantibodies in patients with H. pylori infection.

  16. Localization of MHC class II/human cartilage glycoprotein-39 complexes in synovia of rheumatoid arthritis patients using complex-specific monoclonal antibodies

    NARCIS (Netherlands)

    Steenbakkers, Peter G. A.; Baeten, Dominique; Rovers, Eric; Veys, Eric M.; Rijnders, Antonius W. M.; Meijerink, Jan; de Keyser, Filip; Boots, Annemieke M. H.

    2003-01-01

    Recently human cartilage gp-39 (HC gp-39) was identified as a candidate autoantigen in rheumatoid arthritis (RA). To further investigate the relevance of this Ag in RA, we have generated a set of five mAbs to a combination epitope of complexes of HC gp-39(263-275) and the RA-associated DR alpha beta

  17. Risk factors for fractures in patients with rheumatoid arthritis (preliminary results of the multicenter program «Osteoporosis in rheumatoid arthritis: Diagnosis, risk factors, fractures, treatment»

    Directory of Open Access Journals (Sweden)

    Marina Mikhailovna Podvorotova

    2013-01-01

    Full Text Available In patients with rheumatoid arthritis (RA, bone fractures occur 1.5-2 times more frequently than in the population. They often lead to reduced quality of life, to disability and death in the patients. It should be noted that risk factors (RFs for fractures have not been studied on a sufficient sample in Russia; there are no recommendations on the prevention of fractures in this category of patients. Objective: to compare groups of RA patients with and without a history of fractures to further identify possible RFs for fractures. Subjects and methods. The trial included 254 patients aged 18 to 85 years, diagnosed with RA, from the database of the multicenter program «Osteoporosis in rheumatoid arthritis: Diagnosis, risk factors, fractures, treatment», who had been followed up in 2010 to 2011. The patients were divided into two groups: 1 101 (39.8% patients with a history of low-trauma fractures and 2 153 (60.2% patients without a history of fractures. In Group 1, the patients were older than in Group 2 (mean age 59.8 and 56.1 years, respectively. Menopause was recorded in 88.1 and 77.8% of cases, respectively. The groups differed in the duration of RA an average of 15.5 and 11.5 years, respectively Results. The fractures in the history were associated with the use of glucocorticoids (GC, their higher cumulative dose and use duration. In Group 1 patients, the bone mineral density (BMD was lower in all study skeleton portions and more frequently corresponded to osteoporosis. RA complications, such as amyloidosis and osteonecrosis, were more common in the patients with a history of fractures. Conclusion. In RA patients, the most likely RFs of fractures are age, the long-term intake of large-dose GC, low BMD, the severe course of RA, and the presence of its complications.

  18. Leishmaniasis in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    M. Cutolo

    2011-09-01

    Full Text Available Leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. Visceral leishmaniasis is of higher priority than cutaneous leishmaniasis as it is a fatal disease in the absence of treatment. The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. TNF-α has been implicated in cytokine-induced macrophage activation and tissue granuloma formation, two activities linked to control of intracellular visceral infection caused by Leishmania donovani. Anti- tumor necrosis factor-alpha (TNF-α strategies have had a marked and substantial impact in the treatment of rheumatoid arthritis, however the clinical use of TNF-α antagonists has been accompanied by increased reporting of infections. Here we report the first case of visceral leishmaniasis in a patient treated for a long period of time with human anti TNF-α monoclonal antibody, adalimumab. Due to the low incidence rate of Mediterranean visceral leishmaniasis, a systematic screening for leishmaniasis in all patients treated with biologics may be not recommended. However, for those patients living at high risk of leishmaniasis exposure, a periodical serological monitoring should be performed during therapy with anti-TNF monoclonal antibodies.

  19. Quality of life and Related Factors in Rheumatoid Arthritis Patients

    Directory of Open Access Journals (Sweden)

    Mosharafeh Chaleshgar kordasiabi

    2016-12-01

    planners, and clinical specialists. Therefore, we aimed to evaluate QOL and the factors affecting it in patients with RA.Methods: This descriptive-analytical study was performed in 185 RA patients (2014 at Shariati Hospital. The participants were chosen through convenience sampling. The data collection tools included a form on demographic and clinical factors, health status (arthritis impact measurement scale2 [AIMS2], and SF20 QOL questionnaire. Data was analyzed in SPSS 16 using descriptive, univariate, and multivariate regression analysis.Results: The patients had a mean age of 46.97±11.47 years, and most of the patients were female (80.5%, 67.6% of whom were housewives. In general, 90% of the patients had diploma or lower education. Mean of physical dimension of QOL was lower and social and role dimensions were higher than other dimensions. Univariate analysis regression showed that QOL have significant negative relationship with age, disease duration, disease activity score (DAS and significant positive relationship with education and health status. In multivariate regression analysis, health status, DAS, and education explained 71.7% of QOL. Conclusion: Our results highlighted the influence of demographic and diseaserelated factors on QOL. Thus, they should be implemented in designing educational programs to increase QOL in RA patients.

  20. Novel anti-HER2 monoclonal antibodies: synergy and antagonism with tumor necrosis factor

    Directory of Open Access Journals (Sweden)

    Ceran Ceyhan

    2012-10-01

    Full Text Available Abstract Background One-third of breast cancers display amplifications of the ERBB2 gene encoding the HER2 kinase receptor. Trastuzumab, a humanized antibody directed against an epitope on subdomain IV of the extracellular domain of HER2 is used for therapy of HER2-overexpressing mammary tumors. However, many tumors are either natively resistant or acquire resistance against Trastuzumab. Antibodies directed to different epitopes on the extracellular domain of HER2 are promising candidates for replacement or combinatorial therapy. For example, Pertuzumab that binds to subdomain II of HER2 extracellular domain and inhibits receptor dimerization is under clinical trial. Alternative antibodies directed to novel HER2 epitopes may serve as additional tools for breast cancer therapy. Our aim was to generate novel anti-HER2 monoclonal antibodies inhibiting the growth of breast cancer cells, either alone or in combination with tumor necrosis factor-α (TNF-α. Methods Mice were immunized against SK-BR-3 cells and recombinant HER2 extracellular domain protein to produce monoclonal antibodies. Anti-HER2 antibodies were characterized with breast cancer cell lines using immunofluorescence, flow cytometry, immunoprecipitation, western blot techniques. Antibody epitopes were localized using plasmids encoding recombinant HER2 protein variants. Antibodies, either alone or in combination with TNF-α, were tested for their effects on breast cancer cell proliferation. Results We produced five new anti-HER2 monoclonal antibodies, all directed against conformational epitope or epitopes restricted to the native form of the extracellular domain. When tested alone, some antibodies inhibited modestly but significantly the growth of SK-BR-3, BT-474 and MDA-MB-361 cells displaying ERBB2 amplification. They had no detectable effect on MCF-7 and T47D cells lacking ERBB2 amplification. When tested in combination with TNF-α, antibodies acted synergistically on SK-BR-3 cells

  1. Differences in human skin between the epidermal growth factor receptor distribution detected by EGF binding and monoclonal antibody recognition

    DEFF Research Database (Denmark)

    Green, M R; Couchman, J R

    1985-01-01

    , the eccrine sweat glands, capillary system, and the hair follicle outer root sheath, generally similar in pattern to that previously reported for full-thickness rat skin and human epidermis. The same areas also bound EGF-R1 but in addition the monoclonal antibody recognized a cone of melanin containing......Two methods have been used to examine epidermal growth factor (EGF) receptor distribution in human scalp and foreskin. The first employed [125I]EGF viable explants and autoradiography to determine the EGF binding pattern while the second used a monoclonal antibody to the human EGF receptor to map...... whether EGF-R1 could recognize molecules unrelated to the EGF receptor, the EGF binding and EGF-R1 recognition profiles were compared on cultures of SVK14 cells, a SV40 transformed human keratinocyte cell line. EGF binding and EGF-R1 monoclonal antibody distribution on these cells was found to be similar...

  2. Hypoxia-Inducible Factor-1 as Regulator of Angiogenesis in Rheumatoid Arthritis - Therapeutic Implications

    NARCIS (Netherlands)

    Westra, J.; Molema, G.; Kallenberg, C. G. M.

    Angiogenesis plays an important role in the pathogenesis of inflammatory diseases, including rheumatoid arthritis ( RA). The site and extent of inflammation and subsequent joint destruction in the rheumatoid synovium is dependent on the development of new vasculature. Inhibition of angiogenesis,

  3. Epitope mapping of functional domains of human factor V with human and mouse monoclonal antibodies

    International Nuclear Information System (INIS)

    Annamalai, A.E.; Rao, A.K.; Chiu, H.C.; Wang, D.; Dutta-Roy, A.K.; Colman, R.W.

    1986-01-01

    The authors previously described two human monoclonal antibodies (MAbs) which inactivated factor V. The authors have now purified the predominant antibody (H2) on protein A Sepharose using a pH gradient and typed it as IgG 1 ,. Immunoprecipitation of 125 I-human factor Va with H2 demonstrated specificity for the heavy chain (D), Mr = 105,000. The authors compared using ELISA the competitive binding to factor Va, of H2, H1 and two mouse MAbs, B38 (directed to E) and B10 (to activation peptide, Cl). All four antibodies recognized distinct epitopes in factor V with steric overlap in some cases. Factor Xa showed a concentration dependent competition for binding of H1, H2 and B38 but not B10 to factor V/Va in ELISA. All MAbs bound to factor V/Va in the absence of Ca ++ . However, Ca ++ at 8 mM increased the binding of H1 and H2 to 165% and 360% and did not have any effect on the binding of either mouse MAbs. Prothrombin at a concentration of up to 400 μg/ml did not inhibit binding of any of these antibodies. Thus, both the light (E) and heavy (D) chains of factor Va but not the activation peptide (Cl) interact with factor Xa as defined by the MAbs. In addition, sites on both chains for Ca ++ are recognized by particular MAbs (H1 and H2). These studies increase their knowledge of the interactions of factor V domains in the formation of prothrombinase complex

  4. Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy

    NARCIS (Netherlands)

    Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

    2010-01-01

    OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total

  5. Association between serum antibodies to periodontal bacteria and rheumatoid factor in NHANES III

    Science.gov (United States)

    Goh, Charlene E.; Kopp, Jacob; Papapanou, Panos N.; Molitor, Jerry A.; Demmer, Ryan T.

    2016-01-01

    Objective Alterations in the microbiome, including the periodontal microbiome, may be a risk factor for rheumatoid arthritis (RA). Most studies that have analyzed this association are relatively small, focus primarily on a single periodontal pathogen (Porphyromonas gingivalis), and are not population-based. We investigated the association between elevated serum IgG antibodies to 19 periodontal species and the prevalence of rheumatoid factor (RF) in a large nationally representative sample of adults. Methods The Third National Health and Nutrition Examination Survey is a cross-sectional sample of the non-institutionalized US population (n=33,994). Our study population included all dentate participants ≥60 years, who did not have RA as defined by a modified version of the American College of Rheumatology 1987 criteria, and had complete data for both serum IgG antibodies against periodontal bacteria and serum RF antibody titer (n=2461). Results Adjusted odds ratios (ORs) (95% CI) summarizing the relationship between the 19 periodontal serum IgGs and RF seropositivity ranged from 0.53 (0.29, 0.97) to 1.27 (0.79, 2.06), and 17 of the 19 observed ORs were periodontal IgGs to be mostly unassociated with RF seropositivity in the nationally representative NHANES III. Elevated antibody levels to P. intermedia and C. ochracea were associated with lower odds of RF seropositivity. PMID:27110949

  6. Rheumatoid Factor

    Science.gov (United States)

    ... PF4 Antibody Hepatitis A Testing Hepatitis B Testing Hepatitis C Testing HER2/neu Herpes Testing High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV Antiretroviral Drug Resistance Testing, Genotypic HIV Viral Load HLA Testing HLA- ...

  7. Inhibition of fibroblast growth factor receptor 3-dependent lung adenocarcinoma with a human monoclonal antibody

    Directory of Open Access Journals (Sweden)

    Yongjun Yin

    2016-05-01

    Full Text Available Activating mutations in fibroblast growth factor receptor 3 (FGFR3 have been identified in multiple types of human cancer and in congenital birth defects. In human lung cancer, fibroblast growth factor 9 (FGF9, a high-affinity ligand for FGFR3, is overexpressed in 10% of primary resected non-small cell lung cancer (NSCLC specimens. Furthermore, in a mouse model where FGF9 can be induced in lung epithelial cells, epithelial proliferation and ensuing tumorigenesis is dependent on FGFR3. To develop new customized therapies for cancers that are dependent on FGFR3 activation, we have used this mouse model to evaluate a human monoclonal antibody (D11 with specificity for the extracellular ligand-binding domain of FGFR3, that recognizes both human and mouse forms of the receptor. Here, we show that D11 effectively inhibits signaling through FGFR3 in vitro, inhibits the growth of FGFR3-dependent FGF9-induced lung adenocarcinoma in mice, and reduces tumor-associated morbidity. Given the potency of FGF9 in this mouse model and the absolute requirement for signaling through FGFR3, this study validates the D11 antibody as a potentially useful and effective reagent for treating human cancers or other pathologies that are dependent on activation of FGFR3.

  8. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis.

    Science.gov (United States)

    Ishikawa, Jun; Takahashi, Nobunori; Matsumoto, Takuya; Yoshioka, Yutaka; Yamamoto, Noriyuki; Nishikawa, Masaya; Hibi, Hideharu; Ishigro, Naoki; Ueda, Minoru; Furukawa, Koichi; Yamamoto, Akihito

    2016-02-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and chronic inflammation, which lead to the progressive destruction of cartilage and bone in the joints. Numerous studies have reported that administrations of various types of MSCs improve arthritis symptoms in animal models, by paracrine mechanisms. However, the therapeutic effects of the secreted factors alone, without the cell graft, have been uncertain. Here, we show that a single intravenous administration of serum-free conditioned medium (CM) from human deciduous dental pulp stem cells (SHED-CM) into anti-collagen type II antibody-induced arthritis (CAIA), a mouse model of rheumatoid arthritis (RA), markedly improved the arthritis symptoms and joint destruction. The therapeutic efficacy of SHED-CM was associated with an induction of anti-inflammatory M2 macrophages in the CAIA joints and the abrogation of RANKL expression. SHED-CM specifically depleted of an M2 macrophage inducer, the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9), exhibited a reduced ability to induce M2-related gene expression and attenuate CAIA. SHED-CM also inhibited the RANKL-induced osteoclastogenesis in vitro. Collectively, our findings suggest that SHED-CM provides multifaceted therapeutic effects for treating CAIA, including the ED-Siglec-9-dependent induction of M2 macrophage polarization and inhibition of osteoclastogenesis. Thus, SHED-CM may represent a novel anti-inflammatory and reparative therapy for RA. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Anti-citrullinated protein antibody and rheumatoid factor in patients with end-stage renal disease.

    Science.gov (United States)

    Romic, Zeljko; Unic, Adriana; Derek, Lovorka; Zivkovic, Marcela; Marijancevic, Domagoj; Kes, Petar; Pehar, Mario

    2009-01-01

    Patients with end-stage renal disease (ESRD) and on hemodialysis (HD) are at increased risk for developing rheumatoid arthritis (RA), as a result of defective immunity. Our aim was to examine if ESRD and the length of HD treatment impact the clinical utility of antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor (RF) as diagnostic tools for RA. We included 94 subjects in our study: 37 healthy volunteers and 57 patients with ESRD who had been undergoing HD for 1-12 years, and without confirmed RA. In order to test our hypothesis, we measured and correlated anti-CCP and RF as laboratory markers of RA. Our study showed that there is no significant difference between values for anti-CCP (p=0.11) and RF (p=0.98) in control subjects as well as in patients undergoing HD, regardless of the length of time that patients had been undergoing HD treatment. Our study indicates that HD does not impair the specificity of anti-CCP and RF for RA in patients where the disease has not yet developed. Future prospective studies may show whether there is any use in determinating RF, and especially anti-CCP, as early predictors of RA in patients with ESRD who are at greater risk of developing this condition.

  10. Production and properties of monoclonal antibodies to human blood coagulation factor VII and factor VIIa

    International Nuclear Information System (INIS)

    Mann, P.; Nesbitt, J.A.; Ge, M.; Kisiel, W.

    1986-01-01

    Human factor VII is a trace vitamin K-dependent protein that circulates in blood as a single-chain precursor to a serine protease. Upon activation, two-chain factor VIIa activates factor x in the presence of tissue factor and calcium. Purified preparations of single-chain (SC) human factor VII and two-chain (TC) factor VIIa were utilized to immunize Balb/c mice. Spleen cells from these immunized mice were fused to a non-secreting NS-1 derivative of X63-Ag8 myeloma cells and grown in selective medium. Analysis of culture supernatants by EIA revealed several hybridomas that were secreting IgG specific for Sc-factor VII and TC-factor VIIa. In addition, several hybridomas secreted IgG that reacted equally well with factor VII and factor VIIa. One of the latter McAb (A-29) reacted with the heavy chain of factor VIIa and the intact factor VII molecule equally as judged by Western blotting. A-29 was produced in ascites fluid, purified and coupled to activated CH-Sepharose. Application of one liter of normal human plasma to 10 ml of this immunoadsorbent column, elution of factor VII and subsequent Western blot using 125 I-rabbit anti-human factor VII indicated a single species of factor VII(M/sub r/ = 50 KDa) in normal plasma. These specific factor VII/VIIa McAbs may prove useful in the analysis of these factors, and in the separation of SC-factor VII from TC-factor VIIa

  11. Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance

    International Nuclear Information System (INIS)

    Piot, J M; Royer, M; Schmidt-Tanguy, A; Hoppé, E; Gardembas, M; Bourrée, T; Hunault, M; François, S; Boyer, F; Ifrah, N; Renier, G; Chevailler, A; Audran, M; Chappard, D; Libouban, H; Mabilleau, G; Legrand, E; Bouvard, B

    2015-01-01

    Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80–11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density

  12. Humanized versus murine anti-human epidermal growth factor receptor monoclonal antibodies for immunoscintigraphic studies

    Energy Technology Data Exchange (ETDEWEB)

    Morales, Alejo A. Morales; Duconge, Jorge; Alvarez-Ruiz, Daniel; Becquer-Viart, Maria de Los Angeles; Nunez-Gandolff, Gilda; Fernandez, Eduardo; Caballero-Torres, Idania; Iznaga-Escobar, Normando

    2000-02-01

    The anti-human epidermal growth factor receptor (EGF-R) humanized antibody h-R3 (IgG{sub 1}), which binds to an extracellular domain of EGF-R, was used to evaluate the biodistribution on nude mice xenografted with A431 epidermoid carcinoma cell line. Results are compared with its murine version ior egf/r3 monoclonal antibody (mAb). Twenty-one athymic female 4NMRI nu/nu mice were injected intravenously with 10 {mu}g/100 {mu}Ci of {sup 99m}Tc-labeled mAbs. The mAb ior C5 that recognizes an antigen expressed preferentially on the surface of malignant and cytoplasm of normal colorectal cells was used as negative control. Immunoreactivity of {sup 99m}Tc-labeled mAbs was measured by enzyme linked immunosorbent assay on A431 cell line and the immunoreactive fractions determined by Lindmo method. Among all organs significant accumulation was found in tumor (6.14{+-}2.50 %ID/g, 5.06{+-}2.61 %ID/g for murine and humanized mAbs, respectively) 4 h after injection. The immunoreactive fractions were found to be 0.88 and 0.81 for murine and humanized mAb, respectively. Thus, we expect better results using the humanized mAb h-R3 for diagnostic immunoscintigraphy.

  13. Humanized versus murine anti-human epidermal growth factor receptor monoclonal antibodies for immunoscintigraphic studies

    International Nuclear Information System (INIS)

    Morales, Alejo A. Morales; Duconge, Jorge; Alvarez-Ruiz, Daniel; Becquer-Viart, Maria de Los Angeles; Nunez-Gandolff, Gilda; Fernandez, Eduardo; Caballero-Torres, Idania; Iznaga-Escobar, Normando

    2000-01-01

    The anti-human epidermal growth factor receptor (EGF-R) humanized antibody h-R3 (IgG 1 ), which binds to an extracellular domain of EGF-R, was used to evaluate the biodistribution on nude mice xenografted with A431 epidermoid carcinoma cell line. Results are compared with its murine version ior egf/r3 monoclonal antibody (mAb). Twenty-one athymic female 4NMRI nu/nu mice were injected intravenously with 10 μg/100 μCi of 99m Tc-labeled mAbs. The mAb ior C5 that recognizes an antigen expressed preferentially on the surface of malignant and cytoplasm of normal colorectal cells was used as negative control. Immunoreactivity of 99m Tc-labeled mAbs was measured by enzyme linked immunosorbent assay on A431 cell line and the immunoreactive fractions determined by Lindmo method. Among all organs significant accumulation was found in tumor (6.14±2.50 %ID/g, 5.06±2.61 %ID/g for murine and humanized mAbs, respectively) 4 h after injection. The immunoreactive fractions were found to be 0.88 and 0.81 for murine and humanized mAb, respectively. Thus, we expect better results using the humanized mAb h-R3 for diagnostic immunoscintigraphy

  14. Characterization of cell-surface receptors for monoclonal-nonspecific suppressor factor (MNSF)

    International Nuclear Information System (INIS)

    Nakamura, M.; Ogawa, H.; Tsunematsu, T.

    1990-01-01

    Monoclonal-nonspecific suppressor factor (MNSF) is a lymphokine derived from murine T cell hybridoma. The target tissues are both LPS-stimulated B cells and Con A-stimulated T cells. Since the action of MNSF may be mediated by its binding to specific cell surface receptors, we characterized the mode of this binding. The purified MNSF was labeled with 125 I, using the Bolton-Hunter reagent. The labeled MNSF bound specifically to a single class of receptor (300 receptors per cell) on mitogen-stimulated murine B cells or T cells with an affinity of 16 pM at 24 degrees C, in the presence of sodium azide. Competitive experiments showed that MNSF bound to the specific receptor and that the binding was not shared with IL2, IFN-gamma, and TNF. Various cell types were surveyed for the capacity to specifically bind 125 I-MNSF. 125 I-MNSF bound to MOPC-31C (a murine plasmacytoma line) and to EL4 (a murine T lymphoma line). The presence of specific binding correlates with the capacity of the cells to respond to MNSF. These data support the view that like other polypeptide hormones, the action of MNSF is mediated by specific cell surface membrane receptor protein. Identification of these receptors will provide insight into the apparently diverse activities of MNSF

  15. Aging-dependent decline of IL-10 producing B cells coincides with production of antinuclear antibodies but not rheumatoid factors

    NARCIS (Netherlands)

    van der Geest, Kornelis S. M.; Lorencetti, Pedro G.; Abdulahad, Wayel H.; Horst, Gerda; Huitema, Minke; Roozendaal, Caroline; Kroesen, Bart-Jan; Brouwer, Elisabeth; Boots, Annemieke M. H.

    Aging is associated with development of autoimmunity. Loss of B cell tolerance in the elderly is suggested by an increased prevalence of anti-nuclear antibodies (ANAs) and rheumatoid factors (RFs). Accumulating evidence indicates that B cells also impact autoimmunity via secretion of cytokines. So

  16. Poly(ADP-ribose) polymerase inhibition reduces tumor necrosis factor-induced inflammatory response in rheumatoid synovial fibroblasts

    NARCIS (Netherlands)

    García, S.; Bodaño, A.; Pablos, J. L.; Gómez-Reino, J. J.; Conde, C.

    2008-01-01

    To investigate the effect of poly(ADP-ribose) polymerase (PARP) inhibition on the production of inflammatory mediators and proliferation in tumour necrosis factor (TNF)-stimulated fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Cultured FLS from patients with RA were

  17. Experiences and needs for work participation in employees with rheumatoid arthritis treated with anti-tumour necrosis factor therapy

    NARCIS (Netherlands)

    van der Meer, Marrit; Hoving, Jan L.; Vermeulen, Marjolein I. M.; Herenius, Marieke M. J.; Tak, Paul P.; Sluiter, Judith K.; Frings-Dresen, Monique H. W.

    2011-01-01

    To investigate the experiences and needs with respect to work participation of employees with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. Face-to-face interviews in 14 employees with RA on anti-TNF therapy focused on experiences, offered support and needs with

  18. Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty-Five Years: Changing Contribution From Rheumatoid Factor in Two Multicenter UK Inception Cohorts.

    Science.gov (United States)

    Carpenter, Lewis; Norton, Sam; Nikiphorou, Elena; Jayakumar, Keeranur; McWilliams, Daniel F; Rennie, Kirsten L; Dixey, Josh; Kiely, Patrick; Walsh, David Andrew; Young, Adam

    2017-12-01

    To assess the 5-year progression of erosions and joint space narrowing (JSN) and their associations with rheumatoid factor (RF) status in 2 large, multicenter, early rheumatoid arthritis cohorts, spanning 25 years. Radiographic joint damage was recorded using the Sharp/van der Heijde (SHS) method in the Early Rheumatoid Arthritis Study (ERAS), 1986-2001, and the Early Rheumatoid Arthritis Network (ERAN), 2002-2013. Mixed-effects negative binomial regression estimated changes in radiographic damage over 5 years, including erosions and JSN, separately. RF, along with age, sex, and baseline markers of disease activity were controlled for. A total of 1,216 patients from ERAS and 446 from ERAN had radiographic data. Compared to ERAS, ERAN patients had a lower mean total SHS score at baseline (ERAN 6.2 versus ERAS 10.5; P < 0.001) and mean annual rate of change (ERAN 2.5 per year versus ERAS 6.9 per year; P < 0.001). Seventy-four percent of ERAS and 27% of ERAN patients progressed ≥5 units. Lower scores at baseline in ERAN were largely driven by reductions in JSN (ERAS 3.9 versus ERAN 1.2; P < 0.001), along with erosions (ERAS 1.9 versus ERAN 0.8; P < 0.001). RF was associated with greater progression in each cohort, but the absolute difference in mean annual rate of change for RF-positive patients was substantially higher for ERAS (RF positive 8.6 versus RF negative 5.1; P < 0.001), relative to ERAN (RF positive 2.0 versus RF negative 1.9; P = 0.855). Radiographic progression was shown to be significantly reduced between the 2 cohorts, and was associated with lower baseline damage and other factors, including changes in early disease-modifying antirheumatic drug use. The impact of RF status as a prognostic marker of clinically meaningful change in radiographic progression has markedly diminished in the context of more modern treatment. © 2017, American College of Rheumatology.

  19. Effects of anti-vascular endothelial growth factor monoclonal antibody (bevacizumab on lens epithelial cells

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    Jun JH

    2016-06-01

    Full Text Available Jong Hwa Jun,1 Wern-Joo Sohn,2 Youngkyun Lee,2 Jae-Young Kim21Department of Ophthalmology, School of Medicine, Dongsan Medical Center, Keimyung University, 2Department of Oral Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, South KoreaAbstract: The molecular and cellular effects of anti-vascular endothelial growth factor monoclonal antibody (bevacizumab on lens epithelial cells (LECs were examined using both an immortalized human lens epithelial cell line and a porcine capsular bag model. After treatment with various concentrations of bevacizumab, cell viability and proliferation patterns were evaluated using the water-soluble tetrazolium salt assay and 5-bromo-2'-deoxyuridine enzyme-linked immunosorbent assay, respectively. The scratch assay and Western blot analysis were employed to validate the cell migration pattern and altered expression levels of signaling molecules related to the epithelial–mesenchymal transition (EMT. Application of bevacizumab induced a range of altered cellular events in a concentration-dependent manner. A 0.1–2 mg/mL concentration demonstrated dose-dependent increase in proliferation and viability of LECs. However, 4 mg/mL decreased cell proliferation and viability. Cell migrations displayed dose-dependent retardation from 0.1 mg/mL bevacizumab treatment. Transforming growth factor-β2 expression was markedly increased in a dose-dependent manner, and α-smooth muscle actin, matrix metalloproteinase-9, and vimentin expression levels showed dose-dependent changes in a B3 cell line. Microscopic observation of porcine capsular bag revealed changes in cellular morphology and a decline in cell density compared to the control after 2 mg/mL treatment. The central aspect of posterior capsule showed delayed confluence, and the factors related to EMT revealed similar expression patterns to those identified in the cell line. Based on these results, bevacizumab modulates the proliferation

  20. Role of transforming growth factor-beta (TGF) beta in the physiopathology of rheumatoid arthritis.

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    Gonzalo-Gil, Elena; Galindo-Izquierdo, María

    2014-01-01

    Transforming growth factor-beta (TGF-β) is a cytokine with pleiotropic functions in hematopoiesis, angiogenesis, cell proliferation, differentiation, migration and apoptosis. Although its role in rheumatoid arthritis is not well defined, TGF-β activation leads to functional immunomodulatory effects according to environmental conditions. The function of TGF-β in the development of arthritis in murine models has been extensively studied with controversial results. Recent findings point to a non-relevant role for TGF-β in a mice model of collagen-induced arthritis. The study of TGF-β on T-cell responses has shown controversial results as an inhibitor or promoter of the inflammatory response. This paper presents a review of the role of TGF-β in animal models of arthritis. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  1. Modulation of PBMC-decay accelerating factor (PBMC-DAF) and cytokines in rheumatoid arthritis.

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    Pahwa, Roma; Kumar, Uma; Das, Nibhriti

    2016-03-01

    Studies have suggested that abnormal expression of complement regulatory proteins and cytokines contribute significantly to the path-physiology of rheumatoid arthritis. In this context, Decay accelerating factor (DAF) a complement regulatory protein is gaining increased attention. With the notion that immune effecter mechanisms are all interlinked and circulating peripheral blood mononuclear cells (PBMCs) should have a role in a systemic disease like rheumatoid arthritis, we studied the modulation and significance of PBMC-DAF and cytokines in RA. Seventy-five RA patients and 75 healthy controls were recruited. Expression of DAF and cytokines (IFN-γ, IL-17A and IL-10) in the PBMCs of patients and controls was determined. Correlations among DAF, cytokines, and disease activity were evaluated by standard statistical methods. The effect of IFN-γ, IL-17A, and IL-10 on the expression of DAF in patients and controls was studied in vitro. Expression of PBMC-DAF declined in patients both at mRNA and surface level and correlated negatively with the disease activity. Expression of IFN-γ also declined in patients but correlated positively with DAF and negatively with disease activity. Expression of IL-17A and IL-10 was higher in patients. The levels correlated positively with disease activity and negatively with DAF both in patients and controls. In vitro studies indicated that IFN-γ up-regulated DAF expression in PBMCs, whereas IL-17A and IL-10 had negative effect on the same. The decline in the PBMC-DAF is a contributing factor in manifestations of RA. Cytokine environment contributes to this decline. These findings brought novel insights into the complement-cytokine axis in the path-physiology of RA.

  2. EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: report from the Study Group for Risk Factors for Rheumatoid Arthritis

    Science.gov (United States)

    Gerlag, Danielle M; Raza, Karim; van Baarsen, Lisa G M; Brouwer, Elisabeth; Buckley, Christopher D; Burmester, Gerd R; Gabay, Cem; Catrina, Anca I; Cope, Andrew P; Cornelis, François; Dahlqvist, Solbritt Rantapää; Emery, Paul; Eyre, Stephen; Finckh, Axel; Gay, Steffen; Hazes, Johanna M; van der Helm-van Mil, Annette; Huizinga, Tom W J; Klareskog, Lars; Kvien, Tore K; Lewis, Cathryn; Machold, Klaus P; Rönnelid, Johan; van Schaardenburg, Dirkjan; Schett, Georg; Smolen, Josef S; Thomas, Sue; Worthington, Jane; Tak, Paul P

    2012-01-01

    The Study Group for Risk Factors for Rheumatoid Arthritis was established by the EULAR Standing Committee on Investigative Rheumatology to facilitate research into the preclinical and earliest clinically apparent phases of rheumatoid arthritis (RA). This report describes the recommendation for terminology to be used to define specific subgroups during different phases of disease, and defines the priorities for research in this area. Terminology was discussed by way of a three-stage structured process: A provisional list of descriptors for each of the possible phases preceding the diagnosis of RA were circulated to members of the study group for review and feedback. Anonymised comments from the members on this list were fed back to participants before a 2-day meeting. 18 participants met to discuss these data, agree terminologies and prioritise important research questions. The study group recommended that, in prospective studies, individuals without RA are described as having: genetic risk factors for RA; environmental risk factors for RA; systemic autoimmunity associated with RA; symptoms without clinical arthritis; unclassified arthritis; which may be used in a combinatorial manner. It was recommended that the prefix ‘pre-RA with:’ could be used before any/any combination of the five points above but only to describe retrospectively a phase that an individual had progressed through once it was known that they have developed RA. An approach to dating disease onset was recommended. In addition, important areas for research were proposed, including research of other tissues in which an adaptive immune response may be initiated, and the identification of additional risk factors and biomarkers for the development of RA, its progression and the development of extra-articular features. These recommendations provide guidance on approaches to describe phases before the development of RA that will facilitate communication between researchers and comparisons between

  3. Factors influencing the patient with rheumatoid arthritis in their decision to seek podiatry.

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    Blake, A; Mandy, P J; Stew, G

    2013-12-01

    Despite the level of foot involvement in rheumatoid arthritis (RA), and the literature to support early assessment of foot care needs, local referral of patients to podiatry has been occurring too late to instigate certain preventative interventions. Preliminary fieldwork has highlighted that the primary responsibility for the instigation of this lies with the patient. The present study describes the factors that influence the patient with RA in their decision to self-report foot problems. A case study research strategy was employed. Nine patients attending the outpatient rheumatology department participated in the study and data were gathered through semi-structured interviews. This information was analysed using a framework approach. The key themes derived from the data suggested that there are a variety of factors influencing the patient's decision to self-report foot concerns. Some will act to encourage the action and others will act to oppose it. Other factors can influence the decision either way, depending on the individual patient (psychological state, previous experience, body image changes). In addition, age, gender, and cultural and social aspects are also significant. Due to the multitude of factors influencing the individual's decision to seek help, the patient cannot be given sole responsibility for their foot health if we wish to achieve timely and appropriate podiatry, as recommended in the literature. Responsibility should be three-way; the patient, the members of the rheumatology team and, once in the podiatry service, the podiatrist should maintain this. Copyright © 2013 John Wiley & Sons, Ltd.

  4. A monoclonal antibody to an early pregnancy factor-induced suppressor factor (EPF-S1) disrupts implantation in mice.

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    Athanasas-Platsis, S; Hoskin, M J; Rolfe, B E; Cavanagh, A C; Morton, H

    1995-03-01

    The importance of EPF during pregnancy has been established previously but the importance of the EPF-induced suppressor factor EPF-S1 in pregnancy has to date been unaddressed. Investigations were therefore conducted in order to study this. Monoclonal antibodies to EPF-S1 were produced, and one antibody, designated R2T gamma, was characterized. Mated mice were passively immunized with R2T gamma and the effect on implantation determined. Characterization of anti-EPF-S1 R2T gamma revealed that it cross-reacted with EPF-S1 of different MHC restriction but not with EPF or EPF-S2. When injected into mated mice on days 1 to 4, R2T gamma had no effect on pregnancy but when injections continued to day 5, pregnancy was affected; the number of embryos implanted on day 7 were significantly less than the number of corpora lutea counted, signifying embryonic loss. These studies show that anti-EPF-S1 R2T gamma disrupts implantation in mice when injected on days 1 to 5 of pregnancy but not when injected on days 1 to 4, demonstrating that EPF-S1 exerts its effects around the time of implantation.

  5. Cost of tumor necrosis factor blockers per patient with rheumatoid arthritis in a multistate Medicaid population

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    Bonafede M

    2014-09-01

    Full Text Available Machaon Bonafede,1 George J Joseph,2 Neel Shah,2 Nicole Princic,1 David J Harrison2 1Truven Health Analytics, Cambridge, MA, 2Amgen Inc., Thousand Oaks, CA, USA Background: The purpose of this study was to estimate the annual cost per treated patient for the tumor necrosis factor (TNF blockers, etanercept, adalimumab, and infliximab in rheumatoid arthritis (RA patients covered by Medicaid. Methods: The MarketScan Medicaid Multistate Database was used to identify adult RA patients who used etanercept, adalimumab, or infliximab (index agents from 2007 to 2011. The index date was the first claim preceded by 180 days and followed by 360 days of continuous enrollment. Patients with other conditions for which these agents are approved by the US Food and Drug Administration were excluded. “Continuing” patients had one or more pre-index claim for their index biologic, and "new" patients did not. Cost per treated patient was calculated in the 360 day post-index period for each index agent as the total index drug and administration cost to the payer and the costs of switched-to agents divided by the number of patients who received the index agent. Results: A total of 1,085 patients met the study criteria. Forty-eight percent received etanercept (n=521; 37% received adalimumab (n=405; and 15% received infliximab (n=159. Patient characteristics were similar across groups (mean age 47.4 years, 83% female. The annual cost per treated patient was lowest for etanercept ($18,466, followed by adalimumab ($20,983 and infliximab ($26,516. For all agents, annual costs were lower for new patients ($17,996 for etanercept, $18,992 for adalimumab, and $24,756 for infliximab than for continuing patients ($19,004 for etanercept, $24,438 for adalimumab, and $28,127 for infliximab. Conclusion: Etanercept had lower costs per treated patient than adalimumab or infliximab in both new and continuing Medicaid enrollees with RA. Keywords: cost, tumor necrosis factor

  6. HLA-DRB1 Analysis Identified a Genetically Unique Subset within Rheumatoid Arthritis and Distinct Genetic Background of Rheumatoid Factor Levels from Anticyclic Citrullinated Peptide Antibodies.

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    Hiwa, Ryosuke; Ikari, Katsunori; Ohmura, Koichiro; Nakabo, Shuichiro; Matsuo, Keitaro; Saji, Hiroh; Yurugi, Kimiko; Miura, Yasuo; Maekawa, Taira; Taniguchi, Atsuo; Yamanaka, Hisashi; Matsuda, Fumihiko; Mimori, Tsuneyo; Terao, Chikashi

    2018-04-01

    HLA-DRB1 is the most important locus associated with rheumatoid arthritis (RA) and anticitrullinated protein antibodies (ACPA). However, fluctuations of rheumatoid factor (RF) over the disease course have made it difficult to define fine subgroups according to consistent RF positivity for the analyses of genetic background and the levels of RF. A total of 2873 patients with RA and 2008 healthy controls were recruited. We genotyped HLA-DRB1 alleles for the participants and collected consecutive data of RF in the case subjects. In addition to RF+ and RF- subsets, we classified the RF+ subjects into group 1 (constant RF+) and group 2 (seroconversion). We compared HLA-DRB1 alleles between the RA subsets and controls and performed linear regression analysis to identify HLA-DRB1 alleles associated with maximal RF levels. Omnibus tests were conducted to assess important amino acid positions. RF positivity was 88%, and 1372 and 970 RF+ subjects were classified into groups 1 and 2, respectively. RF+ and RF- showed similar genetic associations to ACPA+ and ACPA- RA, respectively. We found that shared epitope (SE) was more enriched in group 2 than 1, p = 2.0 × 10 -5 , and that amino acid position 11 showed a significant association between 1 and 2, p = 2.7 × 10 -5 . These associations were independent of ACPA positivity. SE showed a tendency to be negatively correlated with RF titer (p = 0.012). HLA-DRB1*09:01, which reduces ACPA titer, was not associated with RF levels (p = 0.70). The seroconversion group was shown to have distinct genetic characteristics. The genetic architecture of RF levels is different from that of ACPA.

  7. A novel monoclonal antibody of human stem cell factor inhibits umbilical cord blood stem cell ex vivo expansion

    Directory of Open Access Journals (Sweden)

    Fan Jie

    2012-12-01

    Full Text Available Abstract Stem cell factor (SCF activates hematopoietic stem cell (HSC self-renewal and is being used to stimulate the ex vivo expansion of HSCs. The mechanism by which SCF supports expansion of HSCs remains poorly understood. In cord blood ex vivo expansion assays, a newly produced anti-SCF monoclonal antibody (clone 23C8 was found to significantly inhibit the expansion of CD34+ cells. This antibody appears to bind directly to a part of SCF that is critical for biological activity toward expansion of CD34+ cells, which is located in the first 104 amino acids from the NH2-terminus.

  8. Anti-cyclic citrullinated peptide antibodies and rheumatoid factor in Sjögren's syndrome.

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    Barcelos, Filipe; Abreu, Isabel; Patto, José Vaz; Trindade, Hélder; Teixeira, Ana

    2009-01-01

    The purpose of this study was to evaluate the prevalence and clinical significance of anti-cyclic citrullinated peptide antibodies (anti-CCP-Abs), IgM and IgA rheumatoid factors (RFs) in primary Sjögren's Syndrome (pSS). We compared clinical and serological characteristics of 31 pSS and 31 Rheumatoid Arthritis (RA) patients. Both, anti-CCP-Abs and RFs (IgM, IgA) directed against Fc determinants of IgG from humans and rabbit were detected by enzyme-linked immunosorbent assay (ELISA). We included 31 blood donors as control group for the evaluation of RFs and anti-CCP-Abs. Nine (29%) pSS patients presented arthritis, and 10 (32,3%) RA patients also had secondary Sjögren's syndrome (sSS) RESULTS: IgM and IgA RFs prevalence was similar in pSS and RA, whichever the antigene (Human or Rabbit IgG) used. However, RA patients with sSS showed a tendency to present more often RF positivity, longer disease duration and higher ESR and CRP when compared with pSS patients with arthritis. Anti-CCP-Abs were detected in 64,5% of RA patients and in only 6,9% of pSS patients (p<0,0005). Anti-CCP-Abs were more often positive in RA patients with sSS (RA/sSS) (8 patients, 80%) than in RA patients without sSS (18 patients, 58,1%), and were absent in pSS patients with arthritis. RF-positive pSS patients presented more often pulmonary involvement and higher inflammatory parameters, and less often neuropathy compared to RF-negative patients. In controls, anti-CCP-Abs were absent and RFs were negligible. Anti-CCP-Abs were detected in only a few pSS patients, none of whom presented arthritis, which contrasts with the high frequency of these antibodies in RA/sSS. These results suggest that anti-CCP-Abs could be useful in the distinction between pSS and RA with sSS. Although not useful for the differential diagnosis between RA and pSS, RFs may have a prognostic role in pSS.

  9. Factors contributing to disability in rheumatoid arthritis patients: An Egyptian multicenter study.

    Science.gov (United States)

    Hammad, Marwa; Eissa, Mervat; Dawa, Ghada A

    2018-04-30

    Minimizing disability and enhancing physical function to its optimal levels is still a challenge in management of rheumatoid arthritis (RA). The aim is to identify factors leading to disability in RA. This is a cross-sectional Egyptian multicenter study carried out on 215 RA patients attending to our inpatient and outpatient rheumatology clinics during 4 months starting from April to July 2017 who agreed to participate in the study; 170 patients were from Cairo University hospitals and 45 from Zagazig University hospitals. We recorded a number of possible risk factors including demographic, clinical, serological and therapeutic factors. The assessment of patients' disability was done using Modified HAQ (MHAQ). A significant positive correlation was found between MHAQ and different markers of activity in addition to age and depression score (P<0.001). Illiteracy accounted for higher MHAQ scores (P=0.001). A higher MHAQ was found in patients with ischemic heart disease (P<0.05). Patients with erosions on X-rays had significantly higher MHAQ scores. Subluxations also accounted for higher MHAQ scores (P=0.000). Aging, illiteracy, disease activity, erosions, subluxations, depression and ischemic heart disease were all related to higher disability. Good control of disease activity which in turn reduces erosions and subluxations is mandatory. Screening for depression and proper use of anti-depressants is of great value. Proper screening and prophylaxis is recommended against ischemic heart disease by controlling modifiable risk factors like obesity, dyslipidaemia, hypertension, smoking and sedentary lifestyle. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Utility of a questionnaire of prognostic factors in the evaluation of patient with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Caballero, Carlo Vinicio; Rozenboim, Jonathan; Afanador, Ernesto; Venegas, Carla; Rocha, Felix; Carpio, Marjorie; Alonso, Luz.

    2005-01-01

    There are few studies that have demonstrated the usefulness of prognostic factors in patients with RA using only variables commonly recorded in the clinical records at the beginning of the disease. The aim of our study was to elaborate a simple questionnaire (PPS: Poor Prognosis Score) to evaluate risk factors at the beginning of the illness classifying it in a mild, moderate or severe. We want to know if this simple questionnaire correlates with known variables of worst outcome such as incapacity, mortality, utilization of health services and surgery. Prognostic factors that have shown an association with the worse outcome of RA in different studies were revised. According to literature and published relative risks (RR) of associations, these can be classified as mild (RR 2.0 and 3.0). In accordance with the levels of association, scores were given to the risk factors being 1 for those prognostic factors with mild association, 2 for those with moderate association, and 3 for those strongly associated with a poor prognosis. The PPS was created with the scores assigned. We excluded from the questionnaire variables not use ID a routine practice in our country such as HLA or although available of high cost for our country as the anti-citrulline antibodies. The chosen variables for the questionnaire were: Mild association: (1 point) age, sex, menopause, smoking, incomplete high school, low socioeconomic status, and depression. Moderate association: (2 points) ESR more than 40, C- Reactive protein 6 mg/dl, knee, elbows and, hands inflammation, and duration of RA more than 6 months without a DMARd treatment. Strong association: (3 points) Rheumatoid factor, presence of hand X- ray hand joints more than 20 joints affected at the beginning of disease, HAQ more than 1, and presence of extraarticular manifestations. Patients were classified in mild RA if the score were less than 10 points, moderate RA between 11 and 20 points and severe RA if the score was more than 20

  11. [Assessment of an intervention on cardiovascular risk factors in patients with rheumatoid arthritis].

    Science.gov (United States)

    Zacarías, Andrea; Narváez, Javier; Rodríguez Moreno, Jesús; Jordana, Montserrat; Nolla, Joan M; Gómez Vaquero, Carmen

    2016-08-05

    To evaluate the effectiveness of an intervention on cardiovascular risk factors (CVRF) in patients with rheumatoid arthritis. After determining their CVRF and cardiovascular risk (CVR) by modified SCORE, we gave the patients a letter for their general practitioners in which they were requested for their cooperation in controlling CVRF and where the therapeutic goal for LDL cholesterol was specified. Three months later, any therapeutic intervention was recorded as well as the results. We included 211 patients, 29% with a high CVR. There were new diagnoses of CVRF in 100 patients (47%). The general practitioner changed the treatment in 2/12 diabetes, 30/84 HBP, 74/167 with elevation of LDL cholesterol and 21/51 with hypertriglyceridemia. The percentage of patients with good control over CVRF was: a) in HBP, 25 to 73%; b) elevation of LDL cholesterol from 10 to 17%; and c) in hypertriglyceridemia, 25 to 38%. Through this intervention, a new CVRF was diagnosed in nearly half of the patients. The effectiveness of the intervention on CVRF was low. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  12. Spontaneous Extensor Tendon Rupture in the Rheumatoid Wrist: Risk Factors and Preventive Role of Extended Tenosynovectomy.

    Science.gov (United States)

    Hsueh, Jung-Hua; Liu, Wen-Chung; Yang, Kuo-Chung; Hsu, Kuei-Chang; Lin, Cheng-Ta; Chen, Lee-Wei

    2016-03-01

    Spontaneous extensor tendon rupture is often seen in rheumatoid arthritis (RA) patients, but the risk factors are not clearly defined. We therefore collected the data of RA patients with previous extensor tendon rupture and those with tenosynovitis and analyzed the relationship between extended tenosynovectomy and spontaneous extensor tendon rupture. We retrospectively reviewed 17 spontaneous extensor tendon rupture episodes in 15 RA patients and 14 tenosynovitis episodes that required tenosynovectomy in 12 RA patients from 1997 to 2013. Correlations between the incidence of tendon rupture, X-ray findings, and clinical findings in the affected wrists before tendon rupture were analyzed statistically using the test for proportion. The following parameters were significantly correlated with spontaneous extensor tendon rupture: disease duration longer than 8 years, persistent tenosynovitis longer than 1 year duration, and Larsen grade greater than 4 (P = 0.02, 0.03, and 0.01, respectively). Dislocation of the distal end of the ulna, carpal collapse, and the scallop sign on X-ray contributed to a higher spontaneous extensor tendon rupture rate among RA patients (P = 0.01, 0.05, and 0.03, respectively). Extended tenosynovectomy was performed on 14 wrists in 12 RA patients with persistent tenosynovitis longer than 6 months, and Larsen grade did not deteriorate in this group compared with those who did not undergo the surgery. No spontaneous extensor tendon rupture occurred following the surgery. Risk factors of spontaneous extensor tendon rupture included disease duration longer than 8 years, persistent tenosynovitis longer than 1 year, and wrist Larsen grade greater than 4. Dislocation of the distal end of the ulna, carpal collapse, and the scallop sign on X-ray indicated a higher probability of extensor tendon rupture. Rheumatologists should consult with hand surgeons promptly to preserve hand function before tendon rupture. Prophylactic extended tenosynovectomy

  13. Predictive Factors Related to the Efficacy of Golimumab in Patients with Rheumatoid Arthritis

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    Katsuaki Kanbe

    2015-01-01

    Full Text Available In order to investigate the predictive factors related to clinical efficacy and radiographic progression at 24 weeks by looking at the serum levels of tumor necrosis factor (TNF-α and interleukin (IL-6 including baseline characteristics in patients with rheumatoid arthritis (RA treated with golimumab, serum concentrations of TNF-α and IL-6 were analyzed every 4 weeks up to 24 weeks in 47 patients treated with golimumab. Baseline levels of the Disease Activity Score 28 C-reactive protein (DAS28-CRP and Simplified Disease Activity Index (SDAI scores were also assessed. Radiographic progression using the van der Heijde-modified Sharp (vdH-S score was assessed in 29 patients. Multiple regression analyses related to the DAS28-CRP score and delta total sharp score at 24 weeks was undertaken using the baseline characteristics of patients and serum concentrations of matrix metalloproteinase (MMP-3, TNF-α, and IL–6. The DAS28-CRP score and SDAI decreased significantly at 4 weeks up to 24 weeks compared with baseline. Serum levels of TNF-α were not changed significantly up to 24 weeks compared with baseline, but those of IL-6 decreased significantly at 4 weeks up to 8 weeks. Multiple regression analyses showed that disease duration and serum levels of MMP-3 were related significantly to the DAS28-CRP score at 24 weeks. Radiographic progression was related significantly to disease duration with regard to joint space narrowing and bone erosion. However, serum levels of TNF-α and IL-6 were not correlated significantly with the DAS28-CRP score and radiographic progression. These data suggest that decreasing serum levels of IL-6 significantly, MMP-3, and disease duration are predictive factors for RA activity in patients taking golimumab.

  14. Rheumatoid arthritis

    Science.gov (United States)

    ... Firestein's Textbook of Rheumatology . 10th ed. Philadelphia, PA: Elsevier; 2017:chap 70. Garneau E. Rheumatoid arthritis. In: ... FF, ed. Ferri's Clinical Advisor 2018 . Philadelphia, PA: Elsevier; 2017:1125-1128. June RR, Moreland LW. Rheumatoid ...

  15. Infliximab treatment in a patient with rheumatoid arthritis on hemodialysis.

    Science.gov (United States)

    Singh, Ranju; Cuchacovich, Raquel; Huang, Wenqun; Espinoza, Luis R

    2002-03-01

    We describe a 60-year-old woman with active rheumatoid arthritis (RA) and endstage renal disease secondary to hypertensive nephrosclerosis undergoing hemodialysis. She had tried multiple antirheumatic medications; however, their usefulness was limited due to toxic side effects or lack of efficacy. She was then treated with chimeric antitumor necrosis factor monoclonal antibody (infliximab), which resulted in immediate improvement in clinical and laboratory measures. After about 2 years of therapy, no side effects have been observed. This report expands the spectrum of infliximab to include RA patients with renal insufficiency.

  16. Monoclonal gammopathy in rheumatic diseases.

    Science.gov (United States)

    Yang, Yue; Chen, Long; Jia, Yuan; Liu, Yang; Wen, Lei; Liang, Yaoxian; An, Yuan; Chen, Shi; Su, Yin; Li, Zhanguo

    2018-07-01

    To analyze the clinical spectrum, laboratory characteristics, and outcomes of monoclonal gammopathy (MG) in patients with rheumatic diseases. Screening for the presence of MG was performed in 872 inpatients with rheumatic diseases from January 2010 to July 2017. A total of 41 patients were enrolled. Their clinical and biological features in addition to outcomes were described. For each patient with primary Sjögren syndrome (pSS), 2 age- and sex-matched pSS patients without MG were selected as controls. Risk factors for the presence of MG and malignant hematological neoplasias were assessed. MG was observed in patients with SS, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, primary biliary cirrhosis, polymyositis, hypomyopathic dermatomyositis, psoriatic arthritis, ANCA-associated vasculitis, polyarteritis nodosa, and polymyalgia rheumatic, with SS the most frequent type. Serum M protein was detected in 37 patients. The monoclonal bands identified in serum were 16 IgG (5 κ, 11 λ), 11 IgA (6 κ, 5 λ), 6 IgM (5 κ, 1 λ), and 4 free λ chains. M components were observed in urine in the other 4 patients. High ESR, albumin/globulin inversion, rheumatoid factor positivity, hypergammaglobulinemia, and hypocomplementemia were common features, presented in more than half of the 41 patients. Patients with pSS, when complicated with MG, showed a higher rate of abnormal urine NAG (71.4 vs 15.8%, P = 0.025), higher levels of ESR [55.0 (53.5) mm/h vs 21.0 (31.8) mm/h, P = 0.001], ESSDAI [26.0 (25.0) vs 12.0 (9.0), P = 0.006], and ClinESSDAI scores [24.0 (25.0) vs 10.5 (10.0), P = 0.011]. Multivariate analysis revealed that the disease activity, assessed by either ESSDAI [adjusted OR 1.127 (95%CI 1.015-1.251), P = 0.025] or ClinESSDAI [adjusted OR 1.121 (95%CI 1.011-1.242), P = 0.030], was the only independent risk factor for the presence of MG. During the follow-up, 2 patients had transient serum M protein, 2 had isotype

  17. Chimeric Monoclonal Antibody Cetuximab Targeting Epidermal Growth Factor-Receptor in Advanced Non-Melanoma Skin Cancer.

    Science.gov (United States)

    Wollina, Uwe; Tchernev, Georgi; Lotti, Torello

    2018-01-25

    Non-melanoma skin cancer (NMSC) is the most common malignancy in humans. Targeted therapy with monoclonal antibody cetuximab is an option in case of advanced tumor or metastasis. We present and update of the use of cetuximab in NMSC searching PUBMED 2011-2017. The monoclonal antibody cetuximab against epidermal growth factor receptor (EGFR) has been investigated for its use in NMSC during the years 2011 to 2017 by a PUBMED research using the following items: "Non-melanoma skin cancer AND cetuximab," "cutaneous squamous cell carcinoma AND cetuximab," and "basal cell carcinoma AND cetuximab", and "cetuximab AND skin toxicity". Available data were analyzed including case reports. Current evidence of cetuximab efficacy in NMSC was mainly obtained in cutaneous SCC and to a lesser extend in BCC. Response rates vary for neoadjuvant, adjuvant, mono- and combined therapy with cetuximab. Management of cutaneous toxicities is necessary. Guidelines are available. Cetuximab is an option for recurrent or advanced NMSC of the skin. It seems to be justified particularly in very high-risk tumors. There is a need for phase III trials.

  18. CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid arthritis.

    Science.gov (United States)

    Han, S W; Sa, K H; Kim, S I; Lee, S I; Park, Y W; Lee, S S; Yoo, W H; Soe, J S; Nam, E J; Lee, J; Park, J Y; Kang, Y M

    2012-11-01

    The chemokine receptor [C-C chemokine receptor 5 (CCR5)] is expressed on diverse immune effecter cells and has been implicated in the pathogenesis of rheumatoid arthritis (RA). This study sought to determine whether single-nucleotide polymorphisms (SNPs) in the CCR5 gene and their haplotypes were associated with susceptibility to and severity of RA. Three hundred fifty-seven patients with RA and 383 healthy unrelated controls were recruited. Using a pyrosequencing assay, we examined four polymorphisms -1118 CTAT(ins) (/del) (rs10577983), 303 A>G (rs1799987), 927 C>T (rs1800024), and 4838 G>T (rs1800874) of the CCR5 gene, which were distributed over the promoter region as well as the 5' and 3' untranslated regions. No significant difference in the genotype, allele, and haplotype frequencies of the four selected SNPs was observed between RA patients and controls. CCR5 polymorphisms of -1118 CTAT(del) (P = 0.012; corrected P = 0.048) and 303 A>G (P = 0.012; corrected P = 0.048) showed a significant association with radiographic severity in a recessive model, and, as a result of multivariate logistic regression analysis, were found to be an independent predictor of radiographic severity. When we separated the erosion score from the total Sharp score, the statistical significance of CCR5 polymorphisms showed an increase; -1118 CTAT(ins) (/del) (P = 0.007; corrected P = 0.028) and 303 A>G (P = 0.007; corrected P = 0.028). Neither SNPs nor haplotypes of the CCR5 gene showed a significant association with joint space narrowing score. These results indicate that genetic polymorphisms of CCR5 are an independent risk factor for radiographic severity denoted by modified Sharp score, particularly joint erosion in RA. © 2012 John Wiley & Sons A/S.

  19. Monoclonal antibody

    International Nuclear Information System (INIS)

    Oyamada, Hiyoshimaru

    1987-01-01

    Some aspects of monoclonal antibodies are described, centering on studies made by the author and those presented at the Second International Conference on Monoclonal Antibody Immunoconjugates for Cancer held in March this year (1987). The history of immuno-nuclear medicine and procedures for producing monoclonal antibodies are briefly outlined. Monoclonal antibodies are immunoglobulins. Here, the structure of IgG, which is used most frequently, is described. An IgG is composed of two antigen binding fragments (Fab) and one crystallizable fragment (Fc). The end portion of a Fab reacts with an antigen. One of the major applications of immuno-nuclear medicine is the diagnosis of cancer. As label nucleides, 131 I and 111 I were selected in most cases in the past while 123 I and 99m Tc are currently used more often. Advantages and disadvantages of this diagnosis method is discussed citing studies presented at the First (1986) and Second (1987) International Conference on Monoclonal Antibody Immunoconjugates for Cancer. The present status of the application of monoclonal antibodies to treatment of cancer is also described. (Nogami, K.)

  20. Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels.

    Science.gov (United States)

    Jones, Jonathan D; Hamilton, B JoNell; Challener, Gregory J; de Brum-Fernandes, Artur J; Cossette, Pierre; Liang, Patrick; Masetto, Ariel; Ménard, Henri A; Carrier, Nathalie; Boyle, David L; Rosengren, Sanna; Boire, Gilles; Rigby, William F C

    2014-04-25

    We hypothesized that serum levels of C-X-C motif chemokine 13 (CXCL13), a B-cell chemokine, would delineate a subset of rheumatoid arthritis (RA) patients characterized by increased humoral immunity. Serum from patients with established RA (the Dartmouth RA Cohort) was analyzed for CXCL13, rheumatoid factor (RF) levels, anticitrullinated peptide/protein antibody (ACPA) and total immunoglobulin G (IgG); other parameters were obtained by chart review. A confirmatory analysis was performed using samples from the Sherbrooke Early Undifferentiated PolyArthritis (EUPA) Cohort. The Wilcoxon rank-sum test, a t-test and Spearman's correlation analysis were utilized to determine relationships between variables. In both the Dartmouth and Sherbrooke cohorts, CXCL13 levels were selectively increased in seropositive relative to seronegative RA patients (P = 0.0002 and P < 0.0001 for the respective cohorts), with a strong correlation to both immunoglobulin M (IgM) and IgA RF levels (P < 0.0001). There was a weaker relationship to ACPA titers (P = 0.03 and P = 0.006, respectively) and total IgG (P = 0.02 and P = 0.14, respectively). No relationship was seen with regard to age, sex, shared epitope status or inclusion high-sensitivity C-reactive protein (hsCRP) in either cohort or regarding the presence of baseline erosions in the Sherbrooke Cohort, whereas a modest relationship with Disease Activity Score in 28 joints CRP (DAS28-CRP) was seen in the Dartmouth cohort but not the Sherbrooke cohort. Using both established and early RA cohorts, marked elevations of serum CXCL13 levels resided nearly completely within the seropositive population. CXCL13 levels exhibited a strong relationship with RF, whereas the association with clinical parameters (age, sex, DAS28-CRP and erosions) or other serologic markers (ACPA and IgG) was either much weaker or absent. Elevated serum CXCL13 levels may identify a subset of seropositive RA patients whose disease is shaped by or responsive to RF

  1. Tumour necrosis factor-α inhibitors are glucocorticoid-sparing in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Nilsson, Anna Christine; Christensen, Anne Friesgaard; Junker, Peter

    2011-01-01

    Rheumatoid arthritis (RA) is a chronic disease with autoimmune traits of unknown aetiology which primarily affects synovial joints. Glucocorticoids (GCs) are still widely used in RA treatment despite the expanding use of targeted and very efficient agents. The objective of this study was to assess...

  2. Characteristics and risk factors of rheumatoid arthritis in the United States: an NHANES analysis

    Directory of Open Access Journals (Sweden)

    Bei Xu

    2017-11-01

    Full Text Available Background We examined the United States National Health and Nutrition Examination Survey (NHANES database to determine factors associated with rheumatoid arthritis (RA in adults 20 to 55 years of age. Methods NHANES data collected between 2007 and 2014, excluding the 2011–2012 period, were used. Subjects were divided into those with and without RA. Demographic, clinical, and lifestyle factors were compared between the groups. Results After applying inclusion/exclusion criteria, 8,789 persons were included in the study (8,483 without RA, 306 with RA. Multivariable analysis indicated that advanced age (odds ratio [OR] = 1.09, 95% CI [1.07–1.11], P < 0.001, regular smoking (OR = 2.19, 95% CI [1.49–3.21], P < 0.001, diabetes (OR = 2.00, 95% CI [1.35–2.95], P = 0.001, obesity (reference, normal or underweight; OR = 3.31, 95% CI [2.05–5.36], P < 0.001, and osteoporosis (OR = 3.68, 95% CI [1.64–8.22], P = 0.002 were positively associated with RA. Covered by health insurance (OR = 1.81, 95% CI [1.12–2.93], P = 0.016 and living in poverty (OR = 2.96, 95% CI [1.88–4.65], P < 0.001 were also associated with having RA. Mexican American, Hispanic white or other Hispanic ethnicity (reference, non-Hispanic white; OR = 0.54, 95% CI [0.31–0.96], P = 0.036, appropriate sleep duration (about 6–11 h, OR = 0.46, 95% CI [0.32–0.65], P < 0.001, and insufficient vitamin A intake (reference, recommended; OR = 0.70, 95% CI [0.50–0.98], P = 0.036 were negatively associated with RA. Discussion Some factors associated with RA are potentially modifiable.

  3. Variability of in vivo recovery of factor IX after infusion of monoclonal antibody purified factor IX concentrates in patients with hemophilia B. The Mononine Study Group.

    Science.gov (United States)

    White, G C; Shapiro, A D; Kurczynski, E M; Kim, H C; Bergman, G E

    1995-05-01

    Monoclonal antibody purified factor IX concentrate, Mononine (Armour Pharmaceutical Company, Kankakee, Illinois, USA), is a recently developed replacement factor concentrate for the treatment of patients with hemophilia B. The pharmacokinetic properties of monoclonal antibody purified factor IX concentrate (MAb Factor IX concentrate) have been evaluated in only small samples of patients, and little is known about those factors that might influenced in vivo recovery of factor IX after infusion is a larger patient population. In vivo recovery of factor IX was therefore evaluated for 80 different indications in 72 patients who received MAb Factor IX concentrate for the management of spontaneous or trauma-induced bleeding, or as prophylaxis with surgery. The average recovery after infusions for presurgical pharmacokinetic analysis (mean +/- standard deviation) was 1.28 +/- 0.56 U/dl rise per U/kg infused (range 0.41-2.80), and the average recovery after all infusions for treatment was 1.23 +/- 0.49 U/dl rise per U/kg infused (range - 0.35-2.92). Recovery values for multiple MAb Factor IX doses in a given patient were also variable; the average recovery was 1.22 +/- 0.53 U/dl rise per U/kg given, and standard deviations ranged from 0.03 to 1.26. Patient age, weight, and MAb Factor IX concentrate dose minimally but significantly influenced factor IX recovery. There was no significant effect of either race, history of previous thrombotic complications during treatment with other replacement factor concentrates, or bleeding state on recovery. All of the patients treated with this preparation experienced excellent hemostasis, and no thrombotic complications were observed.

  4. IgM rheumatoid factor removal and performance of the FTA-ABS (IgM) test in congenital syphilis.

    OpenAIRE

    Meyer, M P; Roditi, D; Louw, S

    1992-01-01

    OBJECTIVE--To determine the performance of the FTA-ABS (IgM) test in congenital syphilis after eliminating interference by IgM rheumatoid factor (RF) and preventing competitive inhibition by IgG. DESIGN--The FTA-ABS (IgM) test was carried out before and after RF removal (achieved by immunoprecipitation of the IgG) in infants with congenital syphilis and controls. SETTING--Newborns delivered in the Peninsula Maternal and Neonatal Services in Cape Town and infants presenting at Red Cross War Me...

  5. Sarcopenia in rheumatoid arthritis: prevalence, influence of disease activity and associated factors.

    Science.gov (United States)

    Ngeuleu, Ange; Allali, F; Medrare, L; Madhi, A; Rkain, H; Hajjaj-Hassouni, N

    2017-06-01

    Evaluate the prevalence of sarcopenia on patients with rheumatoid arthritis (RA), the influence of sarcopenia on disease activity and factors associated with sarcopenia. One hundred and twenty-three patients aged over 18 years with RA based on the 1987 ACR/EULAR classification criteria were enrolled. We performed a whole body DXA scan using a dual-energy X-ray absorptiometry (DXA) scanner lunar prodigy to measure fat mass, lean mass, and bone mass in the whole body and body parts. According to the anthropometric equation by Baumgartner et al., sarcopenia was defined as Relative skeletal mass index (RSMI) sarcopenia with the r of Pearson and Spearman. Factors associated and related to sarcopenia were assessed using multiple regression analysis and t independent test. We included 123 patients (107 women). 49 subjects (39.8%) where suffering from sarcopenia, of which 40 women. Most of the sarcopenic patients were between 41 and 50 years old. Sarcopenia on female subjects was not related to parameters of disease activity evaluated by DAS 28, CDAI and SDAI. Most of the sarcopenic patients had normal BMI and abnormal waist circumference. In simple regression analysis sarcopenia was related to BMI, DAS 28 ESR, bone erosion, waist circumference and HAQ. In multiple regression analysis, sarcopenia was positively related to an increase cardiometabolic risk [p = 0.025, OR 0.176, CI (0.038-0.980)], normal BMI [p = 0.004, OR 12.3, CI (2.27-67.6)], over fat BMI [p = 0.004, OR 12.3, CI (2.27-67.6)] and bone erosion [p = 0.012, OR 0.057 CI (0.006-0.532)]. No statistical difference was found according to disease duration and steroids use between sarcopenic and non sarcopenic patients. Sarcopenia is prevalent and related to age, bone erosion, normal/over fat BMI and high cardiometabolic risk according to waist circumference but not with disease activity.

  6. Phase 1 dose-escalation study of the antiplacental growth factor monoclonal antibody RO5323441 combined with bevacizumab in patients with recurrent glioblastoma

    DEFF Research Database (Denmark)

    Lassen, Ulrik; Chinot, Olivier L; McBain, Catherine

    2015-01-01

    BACKGROUND: We conducted a phase 1 dose-escalation study of RO5323441, a novel antiplacental growth factor (PlGF) monoclonal antibody, to establish the recommended dose for use with bevacizumab and to investigate the pharmacokinetics, pharmacodynamics, safety/tolerability, and preliminary clinica...

  7. Genetic variants in toll-like receptors are not associated with rheumatoid arthritis susceptibility or anti-tumour necrosis factor treatment outcome

    DEFF Research Database (Denmark)

    Coenen, Marieke J H; Enevold, Christian; Barrera, Pilar

    2010-01-01

    Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication.......Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication....

  8. Monoclonal antibodies and cancer

    International Nuclear Information System (INIS)

    Haisma, H.J.

    1987-01-01

    The usefulness of radiolabeled monoclonal antibodies for imaging and treatment of human (ovarian) cancer was investigated. A review of tumor imaging with monoclonal antibodies is presented. Special attention is given to factors that influence the localization of the antibodies in tumors, isotope choice and methods of radiolabeling of the monoclonal antibodies. Two monoclonal antibodies, OC125 and OV-TL3, with high specificity for human epithelial ovarian cancer are characterized. A simple radio-iodination technique was developed for clinical application of the monoclonal antibodies. The behavior of monoclonal antibodies in human tumor xenograft systems and in man are described. Imaging of tumors is complicated because of high background levels of radioactivity in other sites than the tumor, especially in the bloodpool. A technique was developed to improve imaging of human tumor xenographs in nude mice, using subtraction of a specific and a non-specific antibody, radiolabeled with 111 In, 67 Ga and 131 I. To investigate the capability of the two monoclonal antibodies, to specifically localize in human ovarian carcinomas, distribution studies in mice bearing human ovarian carcinoma xenografts were performed. One of the antibodies, OC125, was used for distribution studies in ovarian cancer patients. OC125 was used because of availability and approval to use this antibody in patients. The same antibody was used to investigate the usefulness of radioimmunoimaging in ovarian cancer patients. The interaction of injected radiolabeled antibody OC125 with circulating antigen and an assay to measure the antibody response in ovarian cancer patients after injection of the antibody is described. 265 refs.; 30 figs.; 19 tabs

  9. Identifying risk factors for exposure to culturable allergenic moulds in energy efficient homes by using highly specific monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Sharpe, Richard A. [European Centre for Environment and Human Health, University of Exeter Medical School, Truro TR1 3HD (United Kingdom); Cocq, Kate Le [Rothamsted Research, North Wyke, Okehampton EX20 2SB (United Kingdom); Nikolaou, Vasilis [University of Exeter Medical School, The Veysey Building, Salmon Pool Lane, Exeter EX2 4SG (United Kingdom); Osborne, Nicholas J. [European Centre for Environment and Human Health, University of Exeter Medical School, Truro TR1 3HD (United Kingdom); Clinical Pharmacology and Toxicology Research Group, Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW (Australia); Thornton, Christopher R., E-mail: c.r.thornton@exeter.ac.uk [Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD (United Kingdom)

    2016-01-15

    The aim of this study was to determine the accuracy of monoclonal antibodies (mAbs) in identifying culturable allergenic fungi present in visible mould growth in energy efficient homes, and to identify risk factors for exposure to these known allergenic fungi. Swabs were taken from fungal contaminated surfaces and culturable yeasts and moulds isolated by using mycological culture. Soluble antigens from cultures were tested by ELISA using mAbs specific to the culturable allergenic fungi Aspergillus and Penicillium spp., Ulocladium, Alternaria, and Epicoccum spp., Cladosporium spp., Fusarium spp., and Trichoderma spp. Diagnostic accuracies of the ELISA tests were determined by sequencing of the internally transcribed spacer 1 (ITS1)-5.8S-ITS2-encoding regions of recovered fungi following ELISA. There was 100% concordance between the two methods, with ELISAs providing genus-level identity and ITS sequencing providing species-level identities (210 out of 210 tested). Species of Aspergillus/Penicillium, Cladosporium, Ulocladium/Alternaria/Epicoccum, Fusarium and Trichoderma were detected in 82% of the samples. The presence of condensation was associated with an increased risk of surfaces being contaminated by Aspergillus/Penicillium spp. and Cladosporium spp., whereas moisture within the building fabric (water ingress/rising damp) was only associated with increased risk of Aspergillus/Penicillium spp. Property type and energy efficiency levels were found to moderate the risk of indoor surfaces becoming contaminated with Aspergillus/Penicillium and Cladosporium which in turn was modified by the presence of condensation, water ingress and rising damp, consistent with previous literature. - Highlights: • Monoclonal antibodies were used to track culturable allergenic moulds in homes. • Allergenic moulds were recovered from 82% of swabs from contaminated surfaces. • The mAbs were highly specific with 100% agreement to PCR of recovered fungi. • Improvements to energy

  10. Identifying risk factors for exposure to culturable allergenic moulds in energy efficient homes by using highly specific monoclonal antibodies

    International Nuclear Information System (INIS)

    Sharpe, Richard A.; Cocq, Kate Le; Nikolaou, Vasilis; Osborne, Nicholas J.; Thornton, Christopher R.

    2016-01-01

    The aim of this study was to determine the accuracy of monoclonal antibodies (mAbs) in identifying culturable allergenic fungi present in visible mould growth in energy efficient homes, and to identify risk factors for exposure to these known allergenic fungi. Swabs were taken from fungal contaminated surfaces and culturable yeasts and moulds isolated by using mycological culture. Soluble antigens from cultures were tested by ELISA using mAbs specific to the culturable allergenic fungi Aspergillus and Penicillium spp., Ulocladium, Alternaria, and Epicoccum spp., Cladosporium spp., Fusarium spp., and Trichoderma spp. Diagnostic accuracies of the ELISA tests were determined by sequencing of the internally transcribed spacer 1 (ITS1)-5.8S-ITS2-encoding regions of recovered fungi following ELISA. There was 100% concordance between the two methods, with ELISAs providing genus-level identity and ITS sequencing providing species-level identities (210 out of 210 tested). Species of Aspergillus/Penicillium, Cladosporium, Ulocladium/Alternaria/Epicoccum, Fusarium and Trichoderma were detected in 82% of the samples. The presence of condensation was associated with an increased risk of surfaces being contaminated by Aspergillus/Penicillium spp. and Cladosporium spp., whereas moisture within the building fabric (water ingress/rising damp) was only associated with increased risk of Aspergillus/Penicillium spp. Property type and energy efficiency levels were found to moderate the risk of indoor surfaces becoming contaminated with Aspergillus/Penicillium and Cladosporium which in turn was modified by the presence of condensation, water ingress and rising damp, consistent with previous literature. - Highlights: • Monoclonal antibodies were used to track culturable allergenic moulds in homes. • Allergenic moulds were recovered from 82% of swabs from contaminated surfaces. • The mAbs were highly specific with 100% agreement to PCR of recovered fungi. • Improvements to energy

  11. Impact of tumour necrosis factor inhibitor treatment on radiographic progression in rheumatoid arthritis patients in clinical practice

    DEFF Research Database (Denmark)

    Ornbjerg, Lykke Midtbøll; Østergaard, Mikkel; Bøyesen, Pernille

    2013-01-01

    radiographic progression rates during the DMARD (prebaseline to baseline x-ray) and TNF-I (baseline to follow-up x-ray) periods were calculated.RESULTS: 517 RA patients (76% women, 80% IgM rheumatoid factor positive, 65% anticyclic citrullinated peptide positive, 40% current smokers, age 54 years (range 21......OBJECTIVES: To compare radiographic progression during treatment with disease-modifying antirheumatic drugs (DMARD) and subsequent treatment with tumour necrosis factor α inhibitors (TNF-I) in rheumatoid arthritis (RA) patients in clinical practice.METHODS: Conventional radiographs (x......-1002) and the median TNF-I period was 562 days (IQR 405-766). The median radiographic progression rate decreased from 0.7 (IQR 0-2.9) total Sharp score units/year (dTSS) in the DMARD period to 0 (0-0.9) units/year in the TNF-I period (p0) in the DMARD period compared with 158 patients in the TNF-I period (p...

  12. High prevalence of rheumatoid factor associated with clinical manifestations of rheumatic disease in Kaingang and Guarani Indians from Southern Brazil.

    Science.gov (United States)

    Ribas, João Luiz Coelho; Utiyama, Shirley Ramos da Rosa; Nisihara, Renato Mitsunori; Boeira, Maristela; Reason, Iara Taborda de Messias

    2009-02-01

    The aim of the present study was to perform a screening for rheumatoid factor (RF) and anti-nuclear antibody in Kaingang, Guarani and Mestizos individuals from Mangueirinha Reservation, State of Paraná, Brazil, and associate it with demographic and clinical data. Serum samples from 321 aborigines (125 male and 196 female; 4-86 years old) and 180 non-Indians healthy individuals were analysed (62 male and 118 female; 2-81 years old). Antinuclear antibody (ANA) was tested by indirect immunofluorescence, and RF by agglutination in latex and turbidimetry. RF was higher in Kaingang when compared to Guarani (P = 0.009), Mestizos (P = 0.061) and non-Indians (P = 0.010). A significant increase of RF was observed in Kaingang women versus Kaingang men (P = 0.002) and, among the women, in Kaingang when compared to Mestizos and Guarani (P rheumatoid arthritis in two Kaingang Indians. Other two individuals (RF positive) will be under medical observation, as well as two Mestizos. The differences observed among the investigated groups, suggest the influence of genetic and hormonal factors in the development of auto antibodies in these populations.

  13. Association Between Serum Antibodies to Periodontal Bacteria and Rheumatoid Factor in the Third National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Goh, Charlene E; Kopp, Jacob; Papapanou, Panos N; Molitor, Jerry A; Demmer, Ryan T

    2016-10-01

    Alterations in the microbiome, including the periodontal microbiome, may be a risk factor for rheumatoid arthritis (RA). Most studies that have analyzed this association are relatively small, focus primarily on a single periodontal pathogen (Porphyromonas gingivalis), and are not population based. This study was undertaken to investigate the association between elevated serum levels of IgG antibodies to 19 periodontal species and the prevalence of rheumatoid factor (RF) in a large nationally representative sample of adults. The Third National Health and Nutrition Examination Survey (NHANES-III) is a cross-sectional sample of the noninstitutionalized US population (n = 33,994). Our study population included all dentate participants who were 60 years and older, did not have RA as defined by a modified version of the American College of Rheumatology 1987 criteria, and had complete data for both serum IgG antibodies against periodontal bacteria and serum RF antibody titer (n = 2,461). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) summarizing the relationship between the 19 periodontal serum IgG antibodies and RF seropositivity ranged from 0.53 (95% CI 0.29-0.97) to 1.27 (95% CI 0.79-2.06), and 17 of the 19 observed ORs were periodontal bacteria are mostly unassociated with RF seropositivity in the nationally representative NHANES-III. Elevated levels of antibodies to P intermedia and C ochracea are associated with lower odds of RF seropositivity. © 2016, American College of Rheumatology.

  14. Investigation of a panel of monoclonal antibodies and polyclonal sera against anthrax toxins resulted in identification of an anti-lethal factor antibody with disease-enhancing characteristics.

    Science.gov (United States)

    Kulshreshtha, Parul; Tiwari, Ashutosh; Priyanka; Joon, Shikha; Sinha, Subrata; Bhatnagar, Rakesh

    2015-12-01

    Hybridomas were created using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor). Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immnized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies secreted by all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H10 and H8) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). Single chain variable fragment (LETscFv) was derived from H10 hybridoma. H11 was found to have disease-enhancing property. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature. This in vitro abrogation of disease-enhancement provides the proof of concept that in polyclonal sera the disease enhancing character of a fraction of antibodies is overshadowed by the protective nature of the rest of the antibodies generated on active immunization. Copyright © 2015. Published by Elsevier Ltd.

  15. Factors influencing spinal sagittal balance, bone mineral density, and Oswestry Disability Index outcome measures in patients with rheumatoid arthritis.

    Science.gov (United States)

    Masamoto, Kazutaka; Otsuki, Bungo; Fujibayashi, Shunsuke; Shima, Koichiro; Ito, Hiromu; Furu, Moritoshi; Hashimoto, Motomu; Tanaka, Masao; Lyman, Stephen; Yoshitomi, Hiroyuki; Tanida, Shimei; Mimori, Tsuneyo; Matsuda, Shuichi

    2018-02-01

    To identify the factors influencing spinal sagittal alignment, bone mineral density (BMD), and Oswestry Disability Index (ODI) outcome measures in patients with rheumatoid arthritis (RA). We enrolled 272 RA patients to identify the factors influencing sagittal vertical axis (SVA). Out of this, 220 had evaluation of bone mineral density (BMD) and vertebral deformity (VD) on the sagittal plane; 183 completed the ODI questionnaire. We collected data regarding RA-associated clinical parameters and standing lateral X-ray images via an ODI questionnaire from April to December 2012 at a single center. Patients with a history of spinal surgery or any missing clinical data were excluded. Clinical parameters included age, sex, body mass index, RA disease duration, disease activity score 28 erythrocyte sedimentation rate (DAS28-ESR), serum anti-cyclic citrullinated peptide antibody, serum rheumatoid factor, serum matrix metalloproteinase-3, BMD and treatment type at survey, such as methotrexate (MTX), biological disease-modifying anti-rheumatic drugs, and glucocorticoids. We measured radiological parameters including pelvic incidence (PI), lumbar lordosis (LL), and SVA. We statistically identified the factors influencing SVA, BMD, VD, and ODI using multivariate regression analysis. Multivariate regression analysis showed that larger SVA correlated with older age, higher DAS28-ESR, MTX nonuse, and glucocorticoid use. Lower BMD was associated with female, older age, higher DAS28-ESR, and MTX nonuse. VD was associated with older age, longer disease duration, lower BMD, and glucocorticoid use. Worse ODI correlated with older age, larger PI-LL mismatch or larger SVA, higher DAS28-ESR, and glucocorticoid use. In managing low back pain and spinal sagittal alignment in RA patients, RA-related clinical factors and the treatment type should be taken into consideration.

  16. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial

    NARCIS (Netherlands)

    Smolen, Josef S.; Kay, Jonathan; Doyle, Mittie K.; Landewé, Robert; Matteson, Eric L.; Wollenhaupt, Jürgen; Gaylis, Norman; Murphy, Frederick T.; Neal, Jeffrey S.; Zhou, Yiying; Visvanathan, Sudha; Hsia, Elizabeth C.; Rahman, Mahboob U.; Ahern, Michael John; Hall, Stephen; Nash, Peter Thomas; Graninger, Winfried; Ebner, Wolfgang; Machold, Klaus; Zamani, Omid; Atkins, Christopher; Beaulieu, André; Bell, Mary; Fitzcharles, Mary Ann; Keystone, Edward; Khraishi, Majed; McKendry, Robert J. R.; Rahman, Proton; Thomason, Glen T. D.; Thorne, J. Carter; Bookman, Arthur; Faraawi, Rafat; Hannonen, Pekka; Leirisalo-Repo, Marjetta; Järvinen, Pentti; Braun, Jürgen; Burmester, Gerd; Fiehn, Christoph; Gruenke, Mathias; Bäuerle, Michael; Hauer, Rolf-Walter; Kellner, Herbert; Rubbert, Andrea; Schewe, Stefan; Sieper, Joachim; Tony, Hans-Peter; Kekow, Jörn; Ching, Daniel Wai Tho; Jones, Peter Brian Barrie; Singh, Gagrath Pradeep

    2009-01-01

    Tumour necrosis factor alpha (TNFalpha) inhibitors are frequently used to treat rheumatoid arthritis, but whether use of a different TNFalpha inhibitor can improve patient response is unknown. We assess the efficacy and safety of the TNFalpha inhibitor golimumab in patients with active rheumatoid

  17. National cohort study of reproductive risk factors for rheumatoid arthritis in Denmark: a role for hyperemesis, gestational hypertension and pre-eclampsia?

    DEFF Research Database (Denmark)

    Jørgensen, K T; Pedersen, B V; Jacobsen, S

    2010-01-01

    While reproductive factors might plausibly be involved in the aetiology of rheumatoid arthritis (RA), the female predominance remains unexplained. A study was undertaken to address the possible impact of live births, pregnancy losses and pregnancy complications on the subsequent risk of RA...

  18. Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Bos, W. H.; Bartelds, G. M.; Vis, M.; van der Horst, A. R.; Wolbink, G. J.; van de Stadt, R. J.; van Schaardenburg, D.; Dijkmans, B. A. C.; Lems, W. F.; Nurmohamed, M. T.; Aarden, L.; Hamann, D.

    2009-01-01

    To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody (ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated fibrinogen (ACF) and IgG1 :

  19. Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Bos, W.H.; Bartelds, G.M.; Vis, M.; van der Horst, A.R.; Wolbink, G.J.; van de Stadt, R.J.; van Schaardenburg, D.; Dijkmans, B.A.C.; Lems, W.F.; Nurmohamed, M.T.; Aarden, L.; Hamann, D.

    2009-01-01

    Objective: To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody ( ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis ( RA). Methods: IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated

  20. Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Bos, W.H.; Bartelds, G.M.; Vis, M.; Horst, A.; Wolbink, G.; van de Stadt, R.J.; van Schaardenburg, D.; Dijkmans, B.A.C.; Lems, W.F.; Nurmohamed, M.T.; Aarden, L.; Hamann, D.

    2009-01-01

    Objective: To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody (ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). Methods: IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated

  1. Reactivation of pulmonary tuberculosis (TBC) with the use of antagonist of the tumor necrosis factor alpha (FNTα) in rheumatoid arthritis: On purpose of a case

    International Nuclear Information System (INIS)

    Martinez V, Jose B; Medina V, Yimy F; Parga, Roberto; Restrepo, Jose Felix; Iglesias G, Antonio; Rondon, Federico

    2005-01-01

    Woman 56 years old, with history of rheumatoid arthritis who develops reactivation of pulmonary tuberculosis (TBC) after 1 year of treatment with biological therapy (antagonist of the tumor necrosis factor alpha). It is discussed pathophysiologic mechanisms, diagnostic approach, treatment of TBC and some recommendations for the use of biological therapy in patients with rheumatic disease

  2. CD8+ T Cells Specific to Apoptosis-Associated Antigens Predict the Response to Tumor Necrosis Factor Inhibitor Therapy in Rheumatoid Arthritis.

    Directory of Open Access Journals (Sweden)

    Alessandra Citro

    Full Text Available CD8+ T cells specific to caspase-cleaved antigens derived from apoptotic T cells (apoptotic epitopes represent a principal player in chronic immune activation, which is known to amplify immunopathology in various inflammatory diseases. The purpose of the present study was to investigate the relationship involving these autoreactive T cells, the rheumatoid arthritis immunopathology, and the response to tumor necrosis factor-α inhibitor therapy. The frequency of autoreactive CD8+ T cells specific to various apoptotic epitopes, as detected by both enzyme-linked immunospot assay and dextramers of major histocompatibility complex class I molecules complexed with relevant apoptotic epitopes, was longitudinally analyzed in the peripheral blood of rheumatoid arthritis patients who were submitted to etanercept treatment (or other tumor necrosis factor inhibitors as a control. The percentage of apoptotic epitope-specific CD8+ T cells was significantly higher in rheumatoid arthritis patients than in healthy donors, and correlated with the disease activity. More important, it was significantly more elevated in responders to tumor necrosis factor-α inhibitor therapy than in non-responders before the start of therapy; it significantly dropped only in the former following therapy. These data indicate that apoptotic epitope-specific CD8+ T cells may be involved in rheumatoid arthritis immunopathology through the production of inflammatory cytokines and that they may potentially represent a predictive biomarker of response to tumor necrosis factor-α inhibitor therapy to validate in a larger cohort of patients.

  3. Correlation between Anti cyclic-citrullinated-‎eptide and rheumatoid Factor Antibodies ‎‎“levels in” Patients with from Rheumatoid ‎Arthritis

    Directory of Open Access Journals (Sweden)

    Alaa Hashim Abd-Ali

    2017-12-01

    Full Text Available To  identify  diagnostic   utilities  of   Anti   citrullinated   protein   (ACCP   and Rheumatoid   factor  (RF   are  autoantibodies (Abs  directly  against an self-individual antigens,  Analytical  study.  The  questioner  reported  for  50  patients  with  RA were collected  from  Department  of  Rheumatology¸  AL˗Sader  Teaching  Hospital.  Serum levels  of  RF & (ACCP  Abs  were  determinated  by enzyme ˗ linked immunosorbent assay”, while  the  level  of  erythrocyte  sedimentation  rate  (ESR  was determined by westergreen  method.   Distribution  of  RA occur  in  females  more  than  males which  reached  (80%  &  (20%  respectively  according  to  the  patients group. The patients divided  according  to the  age  into  three  groups (50. The  percent for  these  groups  were  (16%¸ (52% & (32%. Among the 50 patients with RA¸ CCP and  ESR  49  patients  (98%  tested  positive  for  (ACCP  antibodies¸ and 22 patients (44%  tested  positive for RF. and 37  patients(74% tested increasing levels of ESR in RA  patients. The  mean  value of (ACCP & ESR shows highly significance  (P<0∙05, while the  RF serum  levels increase significantly. Demonstrate  the (ACCP antibodies assay is a useful test for diagnosing RA. However, the use of RF and (ACCPauto- antibodies  in  combination  further  elevated   the diagnostic  value  for  RA

  4. Feasibility study of the Fab fragment of a monoclonal antibody against tissue factor as a diagnostic tool.

    Science.gov (United States)

    Tsumura, Ryo; Sato, Ryuta; Furuya, Fumiaki; Koga, Yoshikatsu; Yamamoto, Yoshiyuki; Fujiwara, Yuki; Yasunaga, Masahiro; Matsumura, Yasuhiro

    2015-12-01

    Tissue factor (TF) is expressed strongly in various types of cancer, especially cancers that are often refractory to treatment, such as pancreatic cancer. In this study, we compared the differences in the biophysical and pharmacological properties of whole IgG and the Fab fragment of anti-human TF monoclonal antibody (1849 antibodies), in order to determine their suitability for application in the diagnosis and treatment of cancers. In the biophysical examination, we investigated the characteristics of 1849-whole IgG and 1849-Fab by SPR sensing and confocal fluorescence microscopy analysis using recombinant human TF antigen and TF-overexpressing human pancreatic cancer cell line, BxPC3, respectively. After conjugation with Alexa-Flour-647, in vivo imaging was conducted in mice bearing BxPC3 xenograft tumors. Furthermore, the distribution of the conjugates in tumors and major organs was evaluated by ex vivo study. The in vitro experiments showed that 1849 antibodies had high affinity against TF antigen. In addition, 1849-Fab showed a faster dissociation rate from the antigen than 1849-whole IgG. In mice, 1849-Fab-Alexa-Flour-647 showed rapid renal clearance and faster tumor accumulation, achieving a high contrast signal over nearby normal tissues in the early phase and enhanced tumor penetration after administration. On the other hand, 1849-whole IgG-Alexa-Flour-647 showed slow clearance from the blood and sustained high tumor accumulation. These results suggest that 1849-Fab may be a useful tool for pancreatic cancer diagnosis.

  5. Establishment of H2Mab-119, an Anti-Human Epidermal Growth Factor Receptor 2 Monoclonal Antibody, Against Pancreatic Cancer.

    Science.gov (United States)

    Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Chang, Yao-Wen; Harada, Hiroyuki; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

    2017-12-01

    Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast cancer and is associated with poor clinical outcomes. In addition, HER2 expression has been reported in other cancers, such as gastric, colorectal, lung, and pancreatic cancers. An anti-HER2 humanized antibody, trastuzumab, leads to significant survival benefits in patients with HER2-overexpressing breast cancers and gastric cancers. Herein, we established a novel anti-HER2 monoclonal antibody (mAb), H 2 Mab-119 (IgG 1 , kappa), and characterized its efficacy against pancreatic cancers using flow cytometry, Western blot, and immunohistochemical analyses. H 2 Mab-119 reacted with pancreatic cancer cell lines, such as KLM-1, Capan-2, and MIA PaCa-2, but did not react with PANC-1 in flow cytometry analysis. Western blot analysis also revealed a moderate signal for KLM-1 and a weak signal for MIA PaCa-2, although H 2 Mab-119 reacted strongly with LN229/HER2 cells. Finally, immunohistochemical analyses with H 2 Mab-119 revealed sensitive and specific reactions against breast and colon cancers but did not react with pancreatic cancers, indicating that H 2 Mab-119 is useful for detecting HER2 overexpression in pancreatic cancers using flow cytometry and Western blot analyses.

  6. Experimental radioimmunotherapy of a xenografted human glioma using [sup 131]I-labeled monoclonal antibody to epidermal growth factor receptor

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Hiroshi; Nakazawa, Shozo [Nippon Medical School, Tokyo (Japan); Herlyn, D

    1993-09-01

    [sup 131]I-labeled F (ab')[sub 2] fragments of murine monoclonal antibodies (MAb) 425 specific to the epidermal growth factor receptor expressed on human gliomas were used in experimental human malignant glioma immunotherapy. Two injections of 150 [mu]Ci [sup 131]I-labeled 425 F(ab')[sub 2] achieved growth inhibition of U-87MG human malignant glioma xenografts in nude mice. This radiolabeled specific MAb F(ab')[sub 2] was significantly superior to radiolabeled fragments of an anti-hepatitis virus control MAb A5C3 in influencing tumor growth. However, similar treatment of established human malignant glioma xenografts did not inhibit progressive tumor growth significantly. No clear tumor inhibition was produced by unlabeled MAb 425F(ab')[sub 2]. These studies suggest that [sup 131]I-labeled MAbs have a significant antitumor effect where unmodified antibody is ineffective. Multiple doses of antibody may achieve an increase in labeled MAb concentration in tumors. (author).

  7. Targeting connective tissue growth factor (CTGF) in acute lymphoblastic leukemia preclinical models: anti-CTGF monoclonal antibody attenuates leukemia growth.

    Science.gov (United States)

    Lu, Hongbo; Kojima, Kensuke; Battula, Venkata Lokesh; Korchin, Borys; Shi, Yuexi; Chen, Ye; Spong, Suzanne; Thomas, Deborah A; Kantarjian, Hagop; Lock, Richard B; Andreeff, Michael; Konopleva, Marina

    2014-03-01

    Connective tissue growth factor (CTGF/CCN2) is involved in extracellular matrix production, tumor cell proliferation, adhesion, migration, and metastasis. Recent studies have shown that CTGF expression is elevated in precursor B-acute lymphoblastic leukemia (ALL) and that increased expression of CTGF is associated with inferior outcome in B-ALL. In this study, we characterized the functional role and downstream signaling pathways of CTGF in ALL cells. First, we utilized lentiviral shRNA to knockdown CTGF in RS4;11 and REH ALL cells expressing high levels of CTGF mRNA. Silencing of CTGF resulted in significant suppression of leukemia cell growth compared to control vector, which was associated with AKT/mTOR inactivation and increased levels of cyclin-dependent kinase inhibitor p27. CTGF knockdown sensitized ALL cells to vincristine and methotrexate. Treatment with an anti-CTGF monoclonal antibody, FG-3019, significantly prolonged survival of mice injected with primary xenograft B-ALL cells when co-treated with conventional chemotherapy (vincristine, L-asparaginase and dexamethasone). Data suggest that CTGF represents a targetable molecular aberration in B-ALL, and blocking CTGF signaling in conjunction with administration of chemotherapy may represent a novel therapeutic approach for ALL patients.

  8. Rat Monoclonal Antibodies Specific for LST1 Proteins

    OpenAIRE

    Schiller, Christian; Nitschké, Maximilian J. E.; Seidl, Alexander; Kremmer, Elisabeth; Weiss, Elisabeth H.

    2009-01-01

    The LST1 gene is located in the human MHC class III region and encodes transmembrane and soluble isoforms that have been suggested to play a role in the regulation of the immune response and are associated with inflammatory diseases such as rheumatoid arthritis. Here we describe the generation and characterization of the first monoclonal antibodies against LST1. Two hybridoma lines secreting monoclonal antibodies designated 7E2 and 8D12 were established. The 7E2 antibody detects recombinant a...

  9. Evaluation of immunoturbidimetric rheumatoid factor method from Diagam on Abbott c8000 analyzer: comparison with immunonephelemetric method.

    Science.gov (United States)

    Dupuy, Anne Marie; Hurstel, Rémy; Bargnoux, Anne Sophie; Badiou, Stéphanie; Cristol, Jean Paul

    2014-01-01

    Rheumatoid factor (RF) consists of autoantibodies and because of its heterogeneity its determination is not easy. Currently, nephelometry and Elisa method are considered as reference methods. Due to consolidation, many laboratories have fully automated turbidimetric apparatus, and specific nephelemetric systems are not always available. In addition, nephelemetry is more accurate, but time consuming, expensive, and requires a specific device, resulting in a lower efficiency. Turbidimetry could be an attractive alternative. The turbidimetric RF test from Diagam meets the requirements of accuracy and precision for optimal clinical use, with an acceptable measuring range, and could be an alternative in the determination of RF, without the associated cost of a dedicated instrument, making consolidation and saving blood possible.

  10. Preclinical evaluation of radiolabelled nimotuzumab, a promising monoclonal antibody targeting the epidermal growth factor receptor

    Czech Academy of Sciences Publication Activity Database

    Bárta, P.; Lázníčková, A.; Lázníček, M.; Beckford, Denis R.; Beran, Miloš

    2013-01-01

    Roč. 56, č. 5 (2013), s. 280-288 ISSN 0362-4803 Grant - others:GA ČR(CZ) GAP304/10/1738 Institutional support: RVO:61389005 Keywords : radiopharmaceutical * 177Lu * 131I * nimotuzumab * EGFR * preclinical biodistribution Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.187, year: 2013

  11. Monoclonal antibodies directed to human insulin-like growth factor I (IGF I)

    International Nuclear Information System (INIS)

    Laubli, U.K.; Baier, W.; Celio, M.R.; Binz, H.; Humbel, R.E.

    1982-01-01

    Mouse hybridomas secreting antibodies to human insulin-like growth factor I (IGF I) were produced by fusion of spleen cells of hyperimmunised mice with FO mouse-myeloma cells. Eight clones producing antibodies against human IGF I have been isolated, two of which have been characterised. One was used in a radioimmunoassay, the other for immunopurification of IGF. (Auth.)

  12. Serology and immunoglobulin profile in rheumatoid arthritis.

    Science.gov (United States)

    Adhya, S; Chakraborty, G; Hajra, B; Bhattacharya, S; Sikdar, P K; Sinha, S; Banerjee, P P; Ghosh, E; Chakraborty, P

    1998-01-01

    One hundred and twenty cases of clinically diagnosed rheumatoid arthritis, 80 non-rheumatoid cases suffering from various other diseases and 40 healthy individuals were investigated for the presence of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of ANA and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor showed 56.6% positivity in rheumatoid group and 3.7% positivity in non-rheumatoid group. All three serum immunoglobulins (IgG, IgM, IgA) were raised in serum in significant titre in cases of rheumatoid arthritis, whereas only IgA lever was elevated in the group of non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 11.7% and 4.4% cases of rheumatoid arthritis who had severe underlying disease. In non-rheumatoid group, only one of 6 cases of systemic lupus erythematosus showed rheumatoid factor and that too in an insignificant titre (less than 1:20). Synovium and synovial fluid contained plenty of plasma cells and lymphocytes. It has been observed that RF appears first in synovial fluid and it may take several months to a year to attain detectable level in serum.

  13. Rheumatoid Vasculitis

    Science.gov (United States)

    ... in any rheumatoid arthritis patient who develops new constitutional symptoms, skin ulcerations, decreased blood flow to the ... The differential diagnosis of RV includes: Cholesterol embolization syndromes, in which a piece of cholesterol breaks off ...

  14. Rheumatoid arthritis

    African Journals Online (AJOL)

    Mahmood Ally

    being implicated as possible triggers.3 Smoking has recently received much ... rheumatoid synovium and interaction with these antibodies may not only ..... with psycho-social matters and the cessation of smoking should be incorporated in the ...

  15. Molecular characterization of two sub-family specific monoclonal antibodies to meningococcal Factor H binding protein

    Directory of Open Access Journals (Sweden)

    C. Lo Passo

    2018-04-01

    Full Text Available Factor H binding protein (FHbp is a component of two licensed vaccines for prevention of sepsis and meningitis caused by serogroup B meningococci. FHbp binds human Factor H (FH, which contributes to evasion of host immunity and FHbp sequence variants can be classified into two sub-families. Antibodies against FHbp elicit complement-mediated killing and can inhibit recruitment of FH to the bacterial surface. We report epitope mapping studies of two murine IgG mAbs, designated JAR 31 and JAR 36, isolated from a mouse immunized with FHbp in sub-family A, which is present in ∼30–40% of invasive isolates. In the present study, we tested the reactivity of mAbs JAR 31 and JAR 36 with seven natural FHbp sequence variants from different phylogenic groups. We screened bacteriophage-displayed peptide libraries to identify amino acid residues contributing to the JAR 36 epitope. Based on the reactivities of mAbs JAR 31 and JAR 36 with the seven FHbp variants, and the frequent occurrences of aspartate (D and lysine (K residues in the JAR 36-bound phage peptides, we selected six residues in the carboxyl-terminal region of FHbp for replacement with alanine (A. The D201A and K203A substitutions respectively eliminated and decreased binding of mAbs JAR 31 and JAR 36 to FHbp. These substitutions did not affect binding of the control mAb JAR 33 or of human FH. JAR 31 or JAR 36 mediated cooperative complement-mediated bactericidal activity with other anti-FHbp mAbs. The identification of two amino acid residues involved in the epitopes recognized by these anti-FHbp mAbs may contribute to a more complete understanding of the spatial requirements for cooperative anti-FHbp mAb bactericidal activity. Keywords: Biochemistry, Immunology, Microbiology, Molecular biology

  16. Monoclonal antibodies to meningococcal factor H binding protein with overlapping epitopes and discordant functional activity.

    Science.gov (United States)

    Giuntini, Serena; Beernink, Peter T; Reason, Donald C; Granoff, Dan M

    2012-01-01

    Meningococcal factor H binding protein (fHbp) is a promising vaccine candidate. Anti-fHbp antibodies can bind to meningococci and elicit complement-mediated bactericidal activity directly. The antibodies also can block binding of the human complement down-regulator, factor H (fH). Without bound fH, the organism would be expected to have increased susceptibility to bacteriolysis. Here we describe bactericidal activity of two anti-fHbp mAbs with overlapping epitopes in relation to their different effects on fH binding and bactericidal activity. Both mAbs recognized prevalent fHbp sequence variants in variant group 1. Using yeast display and site-specific mutagenesis, binding of one of the mAbs (JAR 1, IgG3) to fHbp was eliminated by a single amino acid substitution, R204A, and was decreased by K143A but not by R204H or D142A. The JAR 1 epitope overlapped that of previously described mAb (mAb502, IgG2a) whose binding to fHbp was eliminated by R204A or R204H substitutions, and was decreased by D142A but not by K143A. Although JAR 1 and mAb502 appeared to have overlapping epitopes, only JAR 1 inhibited binding of fH to fHbp and had human complement-mediated bactericidal activity. mAb502 enhanced fH binding and lacked human complement-mediated bactericidal activity. To control for confounding effects of different mouse IgG subclasses on complement activation, we created chimeric mAbs in which the mouse mAb502 or JAR 1 paratopes were paired with human IgG1 constant regions. While both chimeric mAbs showed similar binding to fHbp, only JAR 1, which inhibited fH binding, had human complement-mediated bactericidal activity. The lack of human complement-mediated bactericidal activity by anti-fHbp mAb502 appeared to result from an inability to inhibit binding of fH. These results underscore the importance of inhibition of fH binding for anti-fHbp mAb bactericidal activity.

  17. Serodiagnosis and immune profile in rheumatoid arthritis.

    Science.gov (United States)

    Chakraborty, P; Bhattacharya, S; Chakraborty, M; Pal, B

    1997-11-01

    One hundred and seventy-five cases of clinically diagnosed rheumatoid arthritis, 82 non-rheumatoid cases suffering from various other diseases and 40 healthy normal controls were investigated for detection of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of antinuclear antibody (ANA) and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor (RF) showed 64% positivity in rheumatoid group and 1.2% positivity in non-rheumatoid group. All three immunoglobulins (IgG, IgM, IgA) were found to be raised in serum of patients with rheumatoid arthritis, whereas only IgA level was elevated in serum of patients with non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 3.4% and 2.8% cases respectively in cases of clinically diagnosed rheumatoid arthritis who had been suffering from severe active rheumatoid arthritis. In non-rheumatoid group RF was positive in significant titre in only one case of leprosy. Synovial fluid and synovium were found to be heavily infiltrated by plasma cells and lymphocytes. RF appears first in synovial fluid and then in serum. Hence RF titre in blood may not attain significant level for the first several months.

  18. Identifying risk factors for exposure to culturable allergenic moulds in energy efficient homes by using highly specific monoclonal antibodies.

    Science.gov (United States)

    Sharpe, Richard A; Cocq, Kate Le; Nikolaou, Vasilis; Osborne, Nicholas J; Thornton, Christopher R

    2016-01-01

    The aim of this study was to determine the accuracy of monoclonal antibodies (mAbs) in identifying culturable allergenic fungi present in visible mould growth in energy efficient homes, and to identify risk factors for exposure to these known allergenic fungi. Swabs were taken from fungal contaminated surfaces and culturable yeasts and moulds isolated by using mycological culture. Soluble antigens from cultures were tested by ELISA using mAbs specific to the culturable allergenic fungi Aspergillus and Penicillium spp., Ulocladium, Alternaria, and Epicoccum spp., Cladosporium spp., Fusarium spp., and Trichoderma spp. Diagnostic accuracies of the ELISA tests were determined by sequencing of the internally transcribed spacer 1 (ITS1)-5.8S-ITS2-encoding regions of recovered fungi following ELISA. There was 100% concordance between the two methods, with ELISAs providing genus-level identity and ITS sequencing providing species-level identities (210 out of 210 tested). Species of Aspergillus/Penicillium, Cladosporium, Ulocladium/Alternaria/Epicoccum, Fusarium and Trichoderma were detected in 82% of the samples. The presence of condensation was associated with an increased risk of surfaces being contaminated by Aspergillus/Penicillium spp. and Cladosporium spp., whereas moisture within the building fabric (water ingress/rising damp) was only associated with increased risk of Aspergillus/Penicillium spp. Property type and energy efficiency levels were found to moderate the risk of indoor surfaces becoming contaminated with Aspergillus/Penicillium and Cladosporium which in turn was modified by the presence of condensation, water ingress and rising damp, consistent with previous literature. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Antibody guided irradiation of brain glioma by arterial infusion of radioactive monoclonal antibody against epidermal growth factor receptor and blood group A antigen

    Energy Technology Data Exchange (ETDEWEB)

    Epenetos, A.A.; Courtenay-Luck, N.; Pickering, D.; Hooker, G.; Lavender, J.P.; McKenzie, C.G. (Hammersmith Hospital, London (UK)); Durbin, H. (Imperial Cancer Research Fund, London (UK). Labs.)

    1985-05-18

    In a patient with recurrent grade IV glioma of the brain resistant to conventional treatment an antibody guided isotopic scan showed uptake by the tumour of a monoclonal antibody (9A) that was developed against epidermal growth factor receptor but cross reacted with blood group A antigen. As a therapeutic attempt antibody labelled with 1665 MBq (45.0 mCi) iodine-131 was delivered to the tumour area by infusion into the internal carotid artery. Computed tomography showed regression of the tumour after treatment, and an appreciable and sustained clinical improvement was noted without any toxicity. Delivery of irradiation guided by monoclonal antibody delivered by arterial infusion of the tumour area may be of clinical value in the treatment of brain gliomas resistant to conventional forms of treatment.

  20. The original Pathologische Anatomie Leiden-Endothelium monoclonal antibody recognizes a vascular endothelial growth factor binding site within neuropilin-1

    NARCIS (Netherlands)

    Jaalouk, Diana E.; Ozawa, Nfichael G.; Sun, Jessica; Lahdenranta, Johanna; Schlingemann, Reinier O.; Pasqualini, Renata; Arap, Wadih

    2007-01-01

    For two decades, the antigen recognized by the Pathologische Anatomie Leiden-Endothelium (PAL-E) monoclonal antibody, a standard vascular endothelial cell marker, has remained elusive. Here, we used a combinatorial phage display-based approach ("epitope mapping") to select peptides binding to the

  1. Deterioration of lung function is associated with presence of IgM rheumatoid factor and smoking in patients with systemic sclerosis

    DEFF Research Database (Denmark)

    Broholm, B.; Ullman, S.; Halberg, P.

    2008-01-01

    of patients with systemic sclerosis (SSc) the influence of smoking and IgM RF on the lung function was calculated. One hundred fifty-five persons with SSc had vital capacity (VC) and diffusing capacity (DLco) measured at least twice with at least 1-year interval as percents of predicted values according......Smoking is a known risk factor for the development of several lung diseases, autoimmune diseases, and IgM rheumatoid factor (RF) in nonrheumatic persons. In patients with rheumatoid arthritis and IgM RF the diffusion capacity is decreased in smokers but not in nonsmokers. In the present study......M RF was found only in smokers or previous smokers, P = 0.007 and P = 0.01, respectively. These findings were confirmed by means of multiple regression analyses. The presence of IgM RF in smoking SSc patients is associated with deteriorating lung function. Whether this is a causal association...

  2. Interleukin-4 but not interleukin-10 inhibits the production of leukemia inhibitory factor by rheumatoid synovium and synoviocytes.

    Science.gov (United States)

    Dechanet, J; Taupin, J L; Chomarat, P; Rissoan, M C; Moreau, J F; Banchereau, J; Miossec, P

    1994-12-01

    The expression of the proinflammatory cytokine leukemia inhibitory factor (LIF) has been reported in the cartilage and synovium of rheumatoid arthritis (RA) patients. Here, we show that high levels of LIF were constitutively produced by cultures of synovium pieces. Low levels of LIF were produced spontaneously by isolated synoviocytes, but interleukin (IL)-1 beta caused a fourfold enhancement of this secretion. The anti-inflammatory cytokine IL-4 reduced the production of LIF by synovium pieces by 75%, as observed earlier with IL-6, IL-1 beta and tumor necrosis factor (TNF)-alpha. IL-4 had a direct effect since it inhibited LIF production by unstimulated and IL-1 beta- or TNF-alpha-stimulated synoviocytes. Conversely, IL-4 enhanced the production of IL-6, which shares with LIF biological activities and receptor components. The inhibitory effect of IL-4 was dose dependent and was reversed using a blocking anti-IL-4 receptor antibody. Similar inhibitory action of IL-4 on LIF production was observed on synovium pieces from patients with osteoarthritis and on normal synoviocytes. IL-10, another anti-inflammatory cytokine acting on monocytes, had no effect on LIF production by either synovium pieces or isolated synoviocytes. Thus, the production of LIF by synovium tissue was inhibited by IL-4 through both a direct effect on synoviocytes and an indirect effect by inhibition of the production of LIF-inducing cytokines.

  3. Experiences and needs for work participation in employees with rheumatoid arthritis treated with anti-tumour necrosis factor therapy.

    Science.gov (United States)

    Van der Meer, Marrit; Hoving, Jan L; Vermeulen, Marjolein I M; Herenius, Marieke M J; Tak, Paul P; Sluiter, Judith K; Frings-Dresen, Monique H W

    2011-01-01

    To investigate the experiences and needs with respect to work participation of employees with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. Face-to-face interviews in 14 employees with RA on anti-TNF therapy focused on experiences, offered support and needs with respect to work participation. Experiences regarding work participation varied and ranged from fatigue at work, having no job control, not being understood by the work environment or difficulty dealing with emotions as a result of interaction within the work environment. Support by health care professionals for work participation was considered important, especially concerning social or psychological issues. Advice in becoming aware of one's changes in abilities was highly appreciated, as was the availability of professional advice in times of an urgent work issue due to RA. Employees mentioned an increase in social support at work and job control as important facilitating factors for work participation. Although patients with RA report improvement in their work functioning after starting anti-TNF therapy, employees continue facing challenges in working life due to RA. For support concerning work participation, it is recommended that health care professionals are more aware of work-related problems in patients with RA treated with anti-TNF therapy.

  4. Treatment effectiveness and treatment patterns among rheumatoid arthritis patients after switching from a tumor necrosis factor inhibitor to another medication

    Directory of Open Access Journals (Sweden)

    Bonafede MMK

    2016-12-01

    Full Text Available Machaon MK Bonafede,1 Jeffrey R Curtis,2 Donna McMorrow,1 Puneet Mahajan,3 Chieh-I Chen4 1Outcomes Research, Truven Health Analytics, Cambridge, MA, 2Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, 3Health Economics and Outcomes Research, Sanofi, Bridgewater, NJ, 4Health Economics and Outcomes Research, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA Objectives: After treatment failure with a tumor necrosis factor inhibitor (TNFi, patients with rheumatoid arthritis (RA can switch to another TNFi (TNFi cyclers or to a targeted disease-modifying antirheumatic drug (DMARD with a non-TNFi mechanism of action (non-TNFi switchers. This study compared treatment patterns and treatment effectiveness between TNFi cyclers and non-TNFi switchers in patients with RA. Methods: The analysis included a cohort of patients from the Truven Health Analytics ­MarketScan Commercial database with RA who switched from a TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab either to another TNFi or to a non-TNFi targeted DMARD (abatacept, tocilizumab, or tofacitinib between January 1, 2010 and September 30, 2014. A claims-based algorithm was used to estimate treatment effectiveness based on six criteria (adherence, no dose increase, no new conventional therapy, no switch to another targeted DMARD, no new/increased oral glucocorticoid, and intra-articular injections on <2 days. Results: The cohort included 5,020 TNFi cyclers and 1,925 non-TNFi switchers. Non-TNFi switchers were significantly less likely than TNFi cyclers to switch therapy again within 6 months (13.2% vs 19.5%; P<0.001 or within 12 months (29.7% vs 34.6%; P<0.001 and significantly more likely to be persistent on therapy at 12 months (61.8% vs 58.2%; P<0.001. Non-TNFi switchers were significantly more likely than TNFi cyclers to achieve all six of the claims-based effectiveness algorithm criteria for the 12 months after

  5. Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis—a proof of principle and exploratory trial: is dose tapering practical in good responders?

    OpenAIRE

    Ibrahim, Fowzia; Lorente-Cánovas, Beatriz; Doré, Caroline J; Bosworth, Ailsa; Ma, Margaret H; Galloway, James B; Cope, Andrew P; Pande, Ira; Walker, David; Scott, David L

    2017-01-01

    Objectives: RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response.Methods: We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0-6) patients were randomized to control (constant TNFi) or two experimental groups...

  6. Treatment-specific changes in circulating adipocytokines: a comparison between tumour necrosis factor blockade and glucocorticoid treatment for rheumatoid arthritis

    NARCIS (Netherlands)

    Klaasen, R.; Herenius, M. M. J.; Wijbrandts, C. A.; de Jager, W.; van Tuyl, L. H.; Nurmohamed, M. T.; Prakken, B. J.; Gerlag, D. M.; Tak, P. P.

    2012-01-01

    Objective There is increasing evidence that adipocytokines may exert proinflammatory and destructive effects in rheumatoid arthritis (RA). Hence, the authors investigated the relationship between adipocytokines and several features associated with RA (inflammation, joint destruction and

  7. β1-Integrin Expression in the Rheumatoid Synovial-Pannus Formation

    OpenAIRE

    Ishikawa, Hitoshi; Hirata, Soichiro; Isobe, Takashi; Nishibayashi, Yasurou; Kubo, Hitoshi; Nannbae, Masahiro; Nakagawa, Natsuko; Andoh, Yoshihiro

    1994-01-01

    In order to investigate the mechanism of synovial pannus formation in rheumatoid arthritis, using an immunohistochemical staining technique with monoclonal antibodies against adhesion molecules, anti-CDw49a (VLA-1), CDw49b (VLA-2), CDw49c (VLA-3), CDw49d (VLA-4) and CDw49e (VLA-5), the pattern of distribution of these molecules at the rheumatoid synovial cartilage junction has been investigated. Twelve samples of rheumatoid articular cartilage covered with pannus were examined. Treatment with...

  8. Identification of a linear epitope recognized by a monoclonal antibody directed to the heterogeneous nucleoriboprotein A2

    DEFF Research Database (Denmark)

    Tronstrøm, Julie; Dragborg, Anette H.; Hansen, Paul Robert

    2014-01-01

    to as RA33. In the absence of citrulline antibodies, RA33 antibodies have been suggested to be associated with a milder disease course. In this study we screened the reactivity of a monoclonal antibody to RA33-derived peptides by modified enzyme-linked immunosorbent assays (ELISA). Terminally truncated......Rheumatoid arthritis (RA) is a chronic autoimmune disorder, characterized by progressive joint destruction and disability. Classical autoantibodies of RA are rheumatoid factors and citrulline antibodies. Patients positive for these autoantibodies are usually associated with a progressive disease...... course. A subgroup of RA patients does not express citrulline antibodies, instead are approximately 35% of these anti-citrulline-negative patients reported to express autoantibodies to the heterogeneous nucleoriboprotein A2, a ribonucleoprotein involved in RNA transport and processing also referred...

  9. Comparing cardiovascular risk factors, disease and treatment in participants with rheumatoid arthritis and without arthritis in a population based study

    LENUS (Irish Health Repository)

    O’Driscoll, N

    2017-05-01

    Rheumatoid Arthritis (RA) is associated with a significant increase in mortality compared to the general population, with cardiovascular disease (CVD) the leading cause of death. The aim of this study is to compare the prevalence and treatment of modifiable CV risk factors and history of CVD in those with RA and those without arthritis in Ireland. Data from the Irish Longitudinal Study on Ageing (TILDA), a population-representative cohort study of people in Ireland aged 50 or over, was used. Participants with RA (n=457) were twice as likely to be obese (OR 2.02, 95% CI 1.99 to 2.06) compared to those without arthritis (n=4,063). Participants with RA were also more likely to be physically inactive (OR 1.73, 95% CI 1.69 to 1.76) and taking antihypertensive medication than those without arthritis. Exercise can have a beneficial impact on CVD and specific interventions to increase physical activity in those with RA may be warranted

  10. Limitations of a hemolytic plaque assay for IgG-anti-IgG rheumatoid factor-producing cells.

    Science.gov (United States)

    Venn, A J; Dresser, D W

    1987-09-24

    An attempt has been made to develop a hemolytic plaque assay capable of detecting homophile IgG rheumatoid factor (RF)-producing cells. Anti-immunoglobulin allotype-developing reagents were used to distinguish between target and effector IgG. The hemolytic assay has been used to demonstrate an apparently high level of homophile IgM and IgG RF-producing cells in the spleens and lymph nodes of mice stimulated by LPS. However, it appears that a large proportion of the plaques obtained in these assays are due to an artefact resulting from cross-linking of target and effector molecules by the developing reagents. In the case of IgM RF the artefact depends on the presence of a small contamination of the target IgG by IgM, allowing cross-linking of target and effector IgM by the anti-mu-specific developing reagent. With the IgG RF, cross-reactivity of the rabbit anti-Ighb allotype-developing serum for the 'wrong' (Igha) allotype, normally undetectable, becomes sufficient to be biologically relevant when the developing antibody is complexed by being bound to its target (Ighb) allotype. Nevertheless anti-allotype reagents may afford an accurate means of detecting homophile IgG RF producing cells using other assay systems.

  11. C-reactive protein, Rheumatoid factor and circulatory immune complex as markers for monitoring treatment of infective endocarditis

    International Nuclear Information System (INIS)

    Alavi, S.M.; Ahmadi, F.; Nashibi, R.

    2010-01-01

    Objectives: To evaluate the diagnostic usefulness of serum C-reactive protein (CRP), rheumatoid factor (RF) and circulatory immune complex (CIC) determinations in monitoring the outcome of infective endocarditis (IE). Methodology: In this prospective analytic descriptive study CRP, RF and CIC were measured on admission and 4 weeks after initiation of standard antibiotic regimen in 30 hospitalized patients with IE in an educational hospital between 2006 and 2007 in Ahvaz a city south west Iran . Duke criteria were used for diagnosis of IE. CRP and RF were examined using quantitative neflometry (Binding site kit, UK) and CIC was detected by semi quantitative immune diffusion (Baharafshan SIRD kit, Iran). Data were evaluated using statistical analyses in SPSS (version 12, USA) software for windows. Results: The fall in serum C-reactive protein or RF was significant (P= 0.05). Only two of the 30 patients, who had elevated CRP, RF and CIC week four failed to response and one needed cardiac surgery. Conclusions: The C-reactive protein proved to be a good tool for monitoring the treatment of IE. Also RF proved useful in the assessment of patients with IE, but the value of CIC was negligible. (author)

  12. Rheumatoid Factor Positivity Is Associated with Increased Joint Destruction and Upregulation of Matrix Metalloproteinase 9 and Cathepsin K Gene Expression in the Peripheral Blood in Rheumatoid Arthritic Patients Treated with Methotrexate

    Directory of Open Access Journals (Sweden)

    Elena V. Tchetina

    2013-01-01

    Full Text Available We evaluated changes in gene expression of mTOR, p21, caspase-3, ULK1, TNFα, matrix metalloproteinase (MMP-9, and cathepsin K in the whole blood of rheumatoid arthritic (RA patients treated with methotrexate (MTX in relation to their rheumatoid factor status, clinical, immunological, and radiological parameters, and therapeutic response after a 24-month follow-up. The study group consisted of 35 control subjects and 33 RA patients without previous history of MTX treatment. Gene expression was measured using real-time RT-PCR. Decreased disease activity in patients at the end of the study was associated with significant downregulation of TNFα expression. Downregulation of mTOR was observed in seronegative patients, while no significant changes in the expression of p21, ULK1, or caspase-3 were noted in any RA patients at the end of the study. The increase in erosion numbers observed in the seropositive patients at the end of the follow-up was accompanied by upregulation of MMP-9 and cathepsin K, while seronegative patients demonstrated an absence of significant changes in MMP-9 and cathepsin K expression and no increase in the erosion score. Our results suggest that increased expression of MMP-9 and cathepsin K genes in the peripheral blood might indicate higher bone tissue destruction activity in RA patients treated with methotrexate. The clinical study registration number is 0120.0810610.

  13. EFFECTIVENESS AND SAFETY OF RECOMBINANT HUMAN GRANULOCYTIC COLONY-STIMULATING FACTOR IN TREATMENT OF GRANULOCYTOPENIA DEVELOPED DURING IMMUNOSUPPRESSIVE THERAPY IN PATIENTS WITH JUVENILE RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    E.I. Alexeeva

    2010-01-01

    Full Text Available Treatment of patients with severe clinical course of juvenile rheumatoid arthritis (JRA is difficult problem. During the last years genetically engineered biological drugs are used equally with traditional immunosuppressive agents in treatment of severe forms of juvenile arthritis. High effectiveness of these drugs can be accompanied with development of unfavorable effects, for example, febrile neutropenia. The article presents results of a study of effectiveness and safety of recombinant human granulocytic colony-stimulating factor — filgrastim (Leucostim — in treatment of granulocytopenia developed during immunosuppressive therapy in 16 patients with JRA. It was shown that administration of filgrastim arrests leucopenia in 100% of patients and granulocytopenia — in 93% of patients in 24 hours after first injection. High effectiveness of drug was combined with good tolerability and safety.Key words: children, treatment, granulocytopenia, filgrastim, juvenile rheumatoid arthritis.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:94-100

  14. Socioeconomic status and risk of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Pedersen, Line Merete Blak; Jacobsen, Søren; Klarlund, Mette

    2006-01-01

    To examine whether markers of socioeconomic status (SES) are associated with risk of rheumatoid arthritis (RA), and if so, whether selected lifestyle-related factors could explain this association.......To examine whether markers of socioeconomic status (SES) are associated with risk of rheumatoid arthritis (RA), and if so, whether selected lifestyle-related factors could explain this association....

  15. Complement-mediated bactericidal activity of anti-factor H binding protein monoclonal antibodies against the meningococcus relies upon blocking factor H binding.

    Science.gov (United States)

    Giuntini, Serena; Reason, Donald C; Granoff, Dan M

    2011-09-01

    Binding of the complement-downregulating protein factor H (fH) to the surface of the meningococcus is important for survival of the organism in human serum. The meningococcal vaccine candidate factor H binding protein (fHbp) is an important ligand for human fH. While some fHbp-specific monoclonal antibodies (MAbs) block binding of fH to fHbp, the stoichiometry of blocking in the presence of high serum concentrations of fH and its effect on complement-mediated bactericidal activity are unknown. To investigate this question, we constructed chimeric antibodies in which the human IgG1 constant region was paired with three murine fHbp-specific binding domains designated JAR 3, JAR 5, and MAb502. By surface plasmon resonance, the association rates for binding of all three MAbs to immobilized fHbp were >50-fold higher than that for binding of fH to fHbp, and the MAb dissociation rates were >500-fold lower than that for fH. While all three MAbs elicited similar C1q-dependent C4b deposition on live bacteria (classical complement pathway), only those antibodies that inhibited binding of fH to fHbp (JAR 3 and JAR 5) had bactericidal activity with human complement. MAb502, which did not inhibit fH binding, had complement-mediated bactericidal activity only when tested with fH-depleted human complement. When an IgG1 anti-fHbp MAb binds to sparsely exposed fHbp on the bacterial surface, there appears to be insufficient complement activation for bacteriolysis unless fH binding also is inhibited. The ability of fHbp vaccines to elicit protective antibodies, therefore, is likely to be enhanced if the antibody repertoire is of high avidity and includes fH-blocking activity.

  16. Prevalence and risk factors of asymptomatic bronchiectasis in patients with rheumatoid arthritis at a tertiary care center in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Suzan Mansour Attar

    2015-01-01

    Full Text Available Introduction and Objectives: Bronchiectasis is a pulmonary manifestation that often occurs in individuals with rheumatoid arthritis (RA. Nevertheless, the prevalence of bronchiectasis in RA patients and predictors of its development/progression remain ill-defined. Our objective was to investigate the prevalence of bronchiectasis in a group of RA patients and examine possible clinical or biochemical risk factors that might contribute to its development. Methods: This was an observational study analyzing 100 RA patients with no pulmonary symptoms selected from King Abdulaziz University Hospital in the Western region of Saudi Arabia from October 2013 to 2014. Demographic, clinical and laboratory information were collected for all patients. Diagnosis was based on the 2010 American College of Rheumatology (ACR/European League Against Rheumatism (EULAR classification system, and disease activity was assessed using the 28-Joint Disease Activity Score Index with C-reactive protein; high-resolution computed tomography chest scans were performed. The prevalence of bronchiectasis was recorded and its association with different risk factors was examined using standard statistical methods. Results: All 100 patients fulfilled the ACR and EULAR classification criteria for RA diagnosis. Their mean age was 51.05 ± 13.5 years, disease duration was 6.19 ± 6.4 years and disease activity index was 4 ± 1.3 (moderate activity. A total of 35 (35% patients developed bronchiectasis. Notably, we observed significant positive associations of bronchiectasis with age, disease duration and male gender (P < 0.001, P = 0.006, P = 0.028, respectively. Conclusions: Asymptomatic bronchiectasis represents a common complication in moderately active RA patients within the Western Region of Saudi Arabia. Furthermore, several predictors of bronchiectasis development were identified, which can contribute to effective risk stratification in RA patients. Further prospective studies are

  17. Tumor necrosis factor blockers influence macrophage responses to Mycobacterium tuberculosis

    OpenAIRE

    HARRIS, JAMES; HARRIS, JAMES

    2008-01-01

    PUBLISHED umor necrosis factor (TNF)?? is a proinflammatory cytokine that mediates inflammation in response to various pathogens, including Mycobacterium tuberculosis, but is also a key factor in the pathogenesis of rheumatoid arthritis and other autoimmune diseases. Three TNF???suppressing drugs have been approved to treat selected autoimmune diseases; 2 are monoclonal antibodies against TNF?? (adalimumab and infliximab), and the other is a soluble TNF receptor/Fc fusion protein (etanerce...

  18. The status of rheumatoid factor and anti-cyclic citrullinated peptide antibody are not associated with the effect of anti-TNFα agent treatment in patients with rheumatoid arthritis: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Qianwen Lv

    Full Text Available OBJECTIVES: This meta-analysis was conducted to investigate whether the status of rheumatoid factor (RF and anti-cyclic citrullinated peptide (anti-CCP antibody are associated with the clinical response to anti-tumor necrosis factor (TNF alpha treatment in rheumatoid arthritis (RA. METHODS: A systemic literature review was performed using the MEDLINE, SCOPUS, Cochrane Library, ISI Web of Knowledge, and Clinical Trials Register databases, and Hayden's criteria of quality assessment for prognostic studies were used to evaluate all of the studies. The correlation between the RF and anti-CCP antibody status with the treatment effect of anti-TNFα agents was analyzed separately using the Mantel Haenszel method. A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was applied. Publication bias was assessed using Egger's linear regression and a funnel plot. RESULTS: A total of 14 studies involving 5561 RA patients meeting the inclusion criteria were included. The overall analysis showed that the pooled relative risk for the predictive effects of the RF and anti-CCP antibody status on patient response to anti-TNFα agents was 0.98 (95% CI: 0.91-1.05, p=0.54 and 0.88 (95% CI: 0.76-1.03, p=0.11, respectively, with I(2 values of 43% (p=0.05 and 67% (p<0.01, respectively. Subgroup analyses of different anti-TNFα treatments (infliximab vs. etanercept vs. adalimumab vs. golimumab, response criteria (DAS28 vs. ACR20 vs. EULAR response, follow-up period (≥ 6 vs. <6 months, and ethnic group did not reveal a significant association for the status of RF and anti-CCP. CONCLUSIONS: Neither the RF nor anti-CCP antibody status in RA patients is associated with a clinical response to anti-TNFα treatment.

  19. Aging-dependent decline of IL-10 producing B cells coincides with production of antinuclear antibodies but not rheumatoid factors.

    Science.gov (United States)

    van der Geest, Kornelis S M; Lorencetti, Pedro G; Abdulahad, Wayel H; Horst, Gerda; Huitema, Minke; Roozendaal, Caroline; Kroesen, Bart-Jan; Brouwer, Elisabeth; Boots, Annemieke M H

    2016-03-01

    Aging is associated with development of autoimmunity. Loss of B cell tolerance in the elderly is suggested by an increased prevalence of anti-nuclear antibodies (ANAs) and rheumatoid factors (RFs). Accumulating evidence indicates that B cells also impact autoimmunity via secretion of cytokines. So far, few studies have directly assessed the effect of aging on the latter B cell function. Here, we determined if and how human aging influences the production of cytokines by B cells. In a cross-sectional study, we found that absolute numbers of circulating B cells were similar in 31 young (ages 19-39) and 73 old (age ≥ 60) individuals. Numbers of transitional B cells (CD19(+)CD27(-)CD38(High)CD24(High)) were decreased in old individuals, whereas numbers of naive and memory B cell subsets were comparable in young and old individuals. Short-term in vitro stimulation of whole blood samples revealed that numbers of B cells capable of producing TNF-α were similar in young and old individuals. In contrast, B cells capable of IL-10 production were decreased in old subjects. This decline of IL-10(+) B cells was observed in old individuals that were ANA positive, and in those that were negative for both ANAs and RFs. However, IL-10(+) B cells were remarkably well retained in the circulation of old subjects that were RF positive. Thus, pro-inflammatory TNF-α(+) B cells are retained in the elderly, whereas IL-10(+) B cells generally decline. In addition, our findings indicate that IL-10(+) B cells may differentially impact the development of ANAs and RFs in the elderly. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Do rheumatoid arthritis patients in clinical practice benefit from switching from infliximab to a second tumor necrosis factor alpha inhibitor?

    DEFF Research Database (Denmark)

    Hjardem, Elisabeth; Østergaard, Mikkel; Pødenphant, Jan

    2007-01-01

    OBJECTIVE: To investigate the efficacy of switching to a second biological drug in rheumatoid arthritis (RA) patients. METHODS: Since 2000, Danish RA patients (n = 1021) receiving biological therapy have been registered in the nationwide DANBIO database. The first and second treatment series of p...

  1. A novel rabbit anti-hepatocyte growth factor monoclonal neutralizing antibody inhibits tumor growth in prostate cancer cells and mouse xenografts

    International Nuclear Information System (INIS)

    Yu, Yanlan; Chen, Yicheng; Ding, Guoqing; Wang, Mingchao; Wu, Haiyang; Xu, Liwei; Rui, Xuefang; Zhang, Zhigen

    2015-01-01

    The hepatocyte growth factor and its receptor c-Met are correlated with castration-resistance in prostate cancer. Although HGF has been considered as an attractive target for therapeutic antibodies, the lack of cross-reactivity of monoclonal antibodies with human/mouse HGFs is a major obstacle in preclinical developments. We generated a panel of anti-HGF RabMAbs either blocking HGF/c-Met interaction or inhibiting c-Met phosphorylation. We selected one RabMAb with mouse cross-reactivity and demonstrated that it blocked HGF-stimulated downstream activation in PC-3 and DU145 cells. Anti-HGF RabMAb inhibited not only the growth of PC-3 cells but also HGF-dependent proliferation in HUVECs. We further demonstrated the efficacy and potency of the anti-HGF RabMAb in tumor xenograft mice models. Through these in vitro and in vivo experiments, we explored a novel therapeutic antibody for advanced prostate cancer. - Highlights: • HGF is an attractive target for castration-refractory prostate cancer. • We generated and characterized a panel of anti-HGF rabbit monoclonal antibodies. • More than half of these anti-HGF RabMAbs was cross-reactive with mouse HGF. • Anti-HGF RabMAb blocks HGF-stimulated phosphorylation and cell growth in vitro. • Anti-HGF RabMAb inhibits tumor growth and angiogenesis in xenograft mice

  2. A novel rabbit anti-hepatocyte growth factor monoclonal neutralizing antibody inhibits tumor growth in prostate cancer cells and mouse xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yanlan; Chen, Yicheng; Ding, Guoqing; Wang, Mingchao; Wu, Haiyang; Xu, Liwei; Rui, Xuefang; Zhang, Zhigen, E-mail: srrshurology@163.com

    2015-08-14

    The hepatocyte growth factor and its receptor c-Met are correlated with castration-resistance in prostate cancer. Although HGF has been considered as an attractive target for therapeutic antibodies, the lack of cross-reactivity of monoclonal antibodies with human/mouse HGFs is a major obstacle in preclinical developments. We generated a panel of anti-HGF RabMAbs either blocking HGF/c-Met interaction or inhibiting c-Met phosphorylation. We selected one RabMAb with mouse cross-reactivity and demonstrated that it blocked HGF-stimulated downstream activation in PC-3 and DU145 cells. Anti-HGF RabMAb inhibited not only the growth of PC-3 cells but also HGF-dependent proliferation in HUVECs. We further demonstrated the efficacy and potency of the anti-HGF RabMAb in tumor xenograft mice models. Through these in vitro and in vivo experiments, we explored a novel therapeutic antibody for advanced prostate cancer. - Highlights: • HGF is an attractive target for castration-refractory prostate cancer. • We generated and characterized a panel of anti-HGF rabbit monoclonal antibodies. • More than half of these anti-HGF RabMAbs was cross-reactive with mouse HGF. • Anti-HGF RabMAb blocks HGF-stimulated phosphorylation and cell growth in vitro. • Anti-HGF RabMAb inhibits tumor growth and angiogenesis in xenograft mice.

  3. EFFICACY EVALUATION OF A MONOCLONAL ANTIBODY AGAINST THE EPIDERMAL GROWTH FACTORS RECEPTOR IN THE MODEL OF SUBCUTANEOUS XENOGRAFT IN IMMUNODEFICIENT MICE

    Directory of Open Access Journals (Sweden)

    Ya. Yu. Ustyugov

    2015-01-01

    Full Text Available This article presents the results of the comparative antitumor efficacy study of two test articles of therapeutic humanized monoclonal antibodies against epidermal growth factor receptor (EGFR manufactured by Russian biopharmaceutical company CJSC “Biocad” and the commercial drug “Erbitux®” (Merck, Germany in subcutaneous xenografts model using human epidermoid carcinoma A431NS cell line. EGFR overexpression in epithelial tumor cells is a commonly known fact that determines use of this receptor as a target for therapeutic monoclonal antibodies. The basic mechanism of action of such drugs is blocking of epithelial cells proliferation through competitive binding to EGFR. Evaluation of tumor growth dynamics in immunodeficient (Nu/Nu mice was performed during in vivo experiment using two parameters: tumor growth index and tumor growth inhibition (TGI, %. The results received with used study design show that antitumor effects of the test articles manufactured by CJSC “Biocad” and the commercial comparator drug “Erbitux®” estimated by values of TGI and tumor growth index are comparable.

  4. Antibody guided diagnosis and therapy of brain gliomas using radiolabeled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase

    International Nuclear Information System (INIS)

    Kalofonos, H.P.; Pawlikowska, T.R.; Hemingway, A.

    1989-01-01

    Twenty-seven patients with brain glioma were scanned using 123 I-labeled monoclonal antibodies against epidermal growth factor receptor (EGFR1) or placental alkaline phosphatase (H17E2). Successful localization was achieved in 18 out of 27 patients. Eleven out of 27 patients were also studied using a nonspecific control antibody (11.4.1) of the same immunoglobulin subclass and observable tumor localization was also achieved in five patients. The specificity of targeting was assessed by comparing images obtained with specific and nonspecific antibodies and by examining tumor and normal tissue biopsies after dual antibody administration. Ten patients with recurrent grade III or IV glioma who showed good localization of radiolabeled antibody were treated with 40-140 mCi of 131 I-labeled antibody delivered to the tumor area intravenously (n = 5) or by infusion into the internal carotid artery (n = 5). Six patients showed clinical improvement lasting from 6 mo to 3 yr. One patient continues in remission (3 yr after therapy), but the other five who responded initially relapsed 6-9 mo after therapy and died. No major toxicity was attributable to antibody-guided irradiation. Targeted irradiation by monoclonal antibody may be clinically useful and should be explored further in the treatment of brain gliomas resistant to conventional forms of treatment

  5. Rheumatoid Arthritis Risk Allele PTPRC Is Also Associated With Response to Anti–Tumor Necrosis Factor α Therapy

    Science.gov (United States)

    Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

    2013-01-01

    Objective Anti–tumor necrosis factor α (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. Methods A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (ΔDAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. Results Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the ΔDAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39–0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41–1.99). Conclusion Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections

  6. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Rheumatoid Arthritis: Additional Conditions Rheumatoid Arthritis: The Immune System Don’t have ... and Health-related Quality of Life Rehabilitation Management for Rheumatoid ...

  7. Long-term treatment of rheumatoid arthritis with adalimumab

    Directory of Open Access Journals (Sweden)

    Murdaca G

    2013-05-01

    Full Text Available Giuseppe Murdaca, Francesca Spanò, Francesco PuppoDepartment of Internal Medicine, Clinical Immunology Unit, University of Genoa, Genoa, ItalyAbstract: Rheumatoid arthritis (RA is a chronic inflammatory disease that is associated with joint damage and progressive disability, an increased risk of morbidity related to comorbid conditions and substantial socioeconomic costs. Tumor necrosis factor-alpha (TNF-α is a proinflammatory cytokine known to have a central role in the initial host response to infection and in the pathogenesis of various immune-mediated diseases, such as RA, ankylosing spondylitis, psoriasis and/or psoriatic arthritis, Crohn’s disease, and systemic lupus erythematosus. Five TNF-α inhibitors are available for the clinical use: infliximab; adalimumab; etanercept; golimumab; and certolizumab pegol. Infliximab is a chimeric human/murine IgG1 monoclonal antibody (mAb; adalimumab, and golimumab are human mAbs; certolizumab pegol is composed of the fragment antigen-binding anti-binding domain of a humanized anti-TNF-α mAb, combined with polyethylene glycol to increase its half-life in the body; etanercept is a fusion protein that acts as a “decoy receptor” for TNF-α. In this paper, we will briefly review the current data on efficacy and safety of adalimumab in patients with RA, its potential beneficial effects upon comorbid conditions, such as endothelial dysfunction and accelerated atherosclerosis in RA, and the immunogenicity.Keywords: adalimumab, efficacy, safety, rheumatoid arthritis, VEGF, immunogenicity, infections

  8. CD6 and syntaxin binding protein 6 variants and response to tumor necrosis factor alpha inhibitors in Danish patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Krintel, Sophine B; Essioux, Laurent; Wool, Assaf

    2012-01-01

    TNFα inhibitor therapy has greatly improved the treatment of patients with rheumatoid arthritis, however at least 30% do not respond. We aimed to investigate insertions and deletions (INDELS) associated with response to TNFα inhibitors in patients with rheumatoid arthritis (RA)....

  9. Urological comorbidities in Egyptian rheumatoid arthritis patients: Risk factors and relation to disease activity and functional status

    Directory of Open Access Journals (Sweden)

    Marwa Niazy

    2017-10-01

    Full Text Available Aim of the work: To assess the urological disorders in rheumatoid arthritis (RA patients, analyse the risk factors and to find their relation to disease activity and functional status. Patients and methods: 291 RA patients (253 females and 38 males; F:M 6.7:1 and 242 matched controls were included. Urological disorders in the form of urinary tract infections (UTI, urolithiasis and acute urine retention (AUR were assessed, risk factors were analysed. Disease activity score (DAS-28 and modified health assessment questionnaire (mHAQ were calculated. Results: RA patients had more frequent urological disorders (38.14% than controls (20.66%, more UTI (p < 0.001 and this difference persisted in females (p < 0.001. Urolithiasis tended to be more frequent in RA patients (p = 0.3; the difference was significant between the female patients and controls (p = 0.04. Urinary stones were comparable between the male patients and controls (p = 0.2. RA patients had more AUR (4.8% than the controls (2.1% (p = 0.07. Asthmatic patients particularly the females had more UTI (p = 0.001 and p < 0.001 respectively. UTIs were observed with higher steroid doses (p = 0.04 and urolithiasis were noticed more in hypertensive female patients (p = 0.03. Patients with higher DAS-28 and mHAQ developed more urological comorbidities (p0.49 and p = 0.82 respectively. UTI and urolithiasis were detected in patients with higher DAS 28 (p = 0.1 and p = 0.4 respectively. Conclusion: RA patients were found to have more urological disorders. Bronchial asthma, hypertension and higher steroid doses may increase risk for urinary comorbidities in RA. Patients with higher DAS28 and mHAQ had more urological comorbidities, however without statistically significant difference.

  10. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... is Happening to the Joints? Rheumatoid Arthritis: Gaining Control – Working with your Rheumatologist Rheumatoid Arthritis: Additional Conditions ... Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of Life Rehabilitation Management for Rheumatoid Arthritis Patients ...

  11. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Play Rheumatoid Arthritis: Symptoms and Diagnosis Rheumatoid Arthritis: What is Happening to the Joints? Rheumatoid Arthritis: Gaining Control – Working with your Rheumatologist Rheumatoid Arthritis: Additional Conditions ...

  12. IgM rheumatoid factor removal and performance of the FTA-ABS (IgM) test in congenital syphilis.

    Science.gov (United States)

    Meyer, M P; Roditi, D; Louw, S

    1992-08-01

    To determine the performance of the FTA-ABS (IgM) test in congenital syphilis after eliminating interference by IgM rheumatoid factor (RF) and preventing competitive inhibition by IgG. The FTA-ABS (IgM) test was carried out before and after RF removal (achieved by immunoprecipitation of the IgG) in infants with congenital syphilis and controls. Newborns delivered in the Peninsula Maternal and Neonatal Services in Cape Town and infants presenting at Red Cross War Memorial Children's Hospital. Infants with congenital syphilis aged 0-4 months were divided into those with clinical signs at presentation and those who were asymptomatic at delivery. In addition, patients without congenital syphilis but with similar clinical signs at presentation were investigated as were control infants. The diagnosis of congenital syphilis was based on the criteria suggested by Kaufman et al (1977). Amongst symptomatic infants with congenital syphilis the FTA-ABS (IgM) test was positive in 34 (92%) of 37 cases prior to abolishing the RF effect and in 29 (78.4%) of 37 cases afterwards (p = 0.19). In 12 cases of congenital syphilis who were asymptomatic at birth, 10 had positive FTA-ABS (IgM) tests before RF removal and only three had positive tests afterwards (p = 0.006). False positive tests were not found amongst 15 symptomatic infants whose clinical features mimicked those of the infants with congenital syphilis. Among 51 healthy infants the test had a false-positive rate of 2% in newborns and 13% in older infants. The false positive reactions were eradicated by IgG precipitation. Following IgG and RF removal there was an improvement in the specificity of the FTA-ABS (IgM) test but this was at the expense of a loss of sensitivity, particularly in asymptomatic newborns. For newborns, if the FTA-ABS (IgM) test was positive, the patient was likely to require treatment for congenital syphilis, regardless of whether the result was due to the presence of RF or specific IgM.

  13. α-transforming growth factor secreted by untransformed bovine anterior pituitary cells in culture. II. Identification using a sequence-specific monoclonal antibody

    International Nuclear Information System (INIS)

    Kobrin, M.S.; Samsoondar, J.; Kudlow, J.E.

    1986-01-01

    Untransformed bovine anterior pituitary cells cultured in serum-free defined medium secrete an epidermal growth factor (EGF)-like peptide with an amino acid composition similar to rat or human α-transforming growth factor (αTGF). To further characterize the bovine pituitary αTGF, it was compared to a human αTGF partially purified from the conditioned medium of a human melanoma cell line. An anti-αTGF monoclonal antibody, MF9, was produced from hybridomas derived from mice immunized with a 17-residue synthetic peptide corresponding to the carboxyl-terminal sequence of rat αTGF. The hybridoma supernatants were initially screened for the ability to immunoprecipitate 125 I-peptide and then tested for recognition of human αTGF. Only 2 of 36 antipeptide antibodies recognized the native αTGF. The binding of 125 I-peptide to MF9 was displaced by human αTGF but not by EGF. Bovine pituitary αTGF also displaced the binding of 125 I-peptide to MF9 in a similar manner to human αTGF. Both iodinated human and bovine pituitary αTGF were immunoprecipitated by MF9 whereas 125 I-EGF was not. Tryptic digests of both 125 I-αTGFs chromatographed to give a single, indistinguishable peak of iodinated material on a reverse-phase C 18 high performance liquid chromatography column when eluted with two different solvent systems, suggesting the generation of a single and identical tyrosine-containing tryptic peptide from both αTGFs. The comparisons of the bovine pituitary and human melanoma αTGF using a sequence-specific monoclonal antibody and peptide mapping suggest that these αTGFs are related and that αTGF production is not limited to transformed or fetal sources

  14. Lessons from the Crystal Structure of the S. aureus Surface Protein Clumping Factor A in Complex With Tefibazumab, an Inhibiting Monoclonal Antibody

    Directory of Open Access Journals (Sweden)

    Vannakambadi K. Ganesh

    2016-11-01

    Full Text Available The Staphylococcus aureus fibrinogen binding MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules, ClfA (clumping factor A is an important virulence factor in staphylococcal infections and a component of several vaccines currently under clinical evaluation. The mouse monoclonal antibody aurexis (also called 12-9, and the humanized version tefibazumab are therapeutic monoclonal antibodies targeting ClfA that in combination with conventional antibiotics were effective in animal models but showed less impressive efficacy in a limited Phase II clinical trial. We here report the crystal structure and a biochemical characterization of the ClfA/tefibazumab (Fab complex. The epitope for tefibazumab is located to the “top” of the N3 subdomain of ClfA and partially overlaps with a previously unidentified second binding site for fibrinogen. A high-affinity binding of ClfA to fibrinogen involves both an interaction at the N3 site and the previously identified docking of the C-terminal segment of the fibrinogen γ-chain in the N2N3 trench. Although tefibazumab binds ClfA with high affinity we observe a modest IC50 value for the inhibition of fibrinogen binding to the MSCRAMM. This observation, paired with a common natural occurring variant of ClfA that is not effectively recognized by the mAb, may partly explain the modest effect tefibazumab showed in the initial clinic trail. This information will provide guidance for the design of the next generation of therapeutic anti-staphylococcal mAbs targeting ClfA.

  15. Insulin-like growth factors (IGFs) as autocrine/paracrine regulators of granulosa cell differentiation and growth: Studies with a neutralizing monoclonal antibody to IGF-I

    International Nuclear Information System (INIS)

    Mondschein, J.S.; Canning, S.F.; Miller, D.Q.; Hammond, J.M.

    1989-01-01

    Evidence that granulosa cells secrete and respond to insulin-like growth factors (IGFs) suggests, but does not prove, the importance of IGFs as intraovarian regulators. To further assess the role of these peptides in ovarian function, a neutralizing monoclonal antibody to IGF-I was employed to block the actions of IGFs in porcine follicular fluid and in granulosa cell-conditioned medium. In one series of experiments, granulosa cells from immature porcine follicles were cultured in medium containing porcine follicular fluid that had been charcoal-treated to remove steroids. As noted before, fluid from large follicles (LFF) stimulated progesterone production in a dose-dependent manner. The stimulatory effect of LFF (30% v/v) could be inhibited by greater than 50% by the anti-IGF monoclonal antibody. This inhibitory action was specific for the anti-IGF antibody and could be overcome by the addition of excess exogenous IGFs. In another series of experiments, granulosa cells were made dependent on endogenously produced IGFs by culturing them in a serum-free medium without exogenous growth factors. The effects of follicle-stimulating hormone (FSH), estradiol (E2), growth hormone (GH), and combinations thereof on progesterone production were inhibited by approximately 50% by the anti-IGF antibody. The effects of IGFs on indices of cell growth (judged by the criterion of being inhibited by the anti-IGF antibody) were less dramatic. A modest 18% increase in cell number was observed with FSH and E2 treatment in serum-free medium; this effect was virtually abolished by the antibody

  16. Insulin-like growth factors (IGFs) as autocrine/paracrine regulators of granulosa cell differentiation and growth: Studies with a neutralizing monoclonal antibody to IGF-I

    Energy Technology Data Exchange (ETDEWEB)

    Mondschein, J.S.; Canning, S.F.; Miller, D.Q.; Hammond, J.M. (Pennsylvania State Univ., Hershey (USA))

    1989-07-01

    Evidence that granulosa cells secrete and respond to insulin-like growth factors (IGFs) suggests, but does not prove, the importance of IGFs as intraovarian regulators. To further assess the role of these peptides in ovarian function, a neutralizing monoclonal antibody to IGF-I was employed to block the actions of IGFs in porcine follicular fluid and in granulosa cell-conditioned medium. In one series of experiments, granulosa cells from immature porcine follicles were cultured in medium containing porcine follicular fluid that had been charcoal-treated to remove steroids. As noted before, fluid from large follicles (LFF) stimulated progesterone production in a dose-dependent manner. The stimulatory effect of LFF (30% v/v) could be inhibited by greater than 50% by the anti-IGF monoclonal antibody. This inhibitory action was specific for the anti-IGF antibody and could be overcome by the addition of excess exogenous IGFs. In another series of experiments, granulosa cells were made dependent on endogenously produced IGFs by culturing them in a serum-free medium without exogenous growth factors. The effects of follicle-stimulating hormone (FSH), estradiol (E2), growth hormone (GH), and combinations thereof on progesterone production were inhibited by approximately 50% by the anti-IGF antibody. The effects of IGFs on indices of cell growth (judged by the criterion of being inhibited by the anti-IGF antibody) were less dramatic. A modest 18% increase in cell number was observed with FSH and E2 treatment in serum-free medium; this effect was virtually abolished by the antibody.

  17. What factors influence the health status of patients with rheumatoid arthritis measured by the SF-12v2 Health Survey and the Health Assessment Questionnaire?

    DEFF Research Database (Denmark)

    Linde, Louise; Sørensen, Jan; Østergaard, Mikkel

    2009-01-01

    OBJECTIVE: The Health Assessment Questionnaire Disability Index (HAQ) is a widely used outcome measure in rheumatoid arthritis (RA), whereas the SF-12v2 Health Survey (SF-12) was introduced recently. We investigated how the HAQ and SF-12 were associated with socio-demographic, lifestyle, and dise...... to differences in demographic, lifestyle, and disease- and treatment-related factors than the SF-12. The established clinical value and feasibility of the HAQ highlights its advantages over the SF-12 in describing health status in RA.......OBJECTIVE: The Health Assessment Questionnaire Disability Index (HAQ) is a widely used outcome measure in rheumatoid arthritis (RA), whereas the SF-12v2 Health Survey (SF-12) was introduced recently. We investigated how the HAQ and SF-12 were associated with socio-demographic, lifestyle......, and disease- and treatment-related factors in patients with RA. METHODS: In RA patients from 11 Danish centers, clinical and patient-reported data, including the HAQ and SF-12, were collected. Three multiple linear regression models were estimated, with the HAQ, SF-12 physical component score (PCS), and SF-12...

  18. EFFECTIVENESS AND SAFETY OF INFLIXIMAB IN PATIENTS WITH EARLY AND LATE JUVENILE RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    Е.I. Alexeeva

    2010-01-01

    Full Text Available The article presents results of a study of effectiveness and safety of infliximab — monoclonal antibodies to the tumor necrotizing factor (TNF in treatment of 100 patients11 months — 17 years old with early and late articular types of juvenile rheumatoid arthritis. The duration of treatment was 3 months — 2 years. Infliximap was delivered intravenously by scheme: infusion on 0, 2nd, 6th weeks and then every 8th week. The single dose of infliximab in patients with early rheumatoid arthritis was 6.7 (5.5; 9.0 mg/kg, with late type — 6.0 (5.0; 7.0 mg/kg of body weight. 102 weeks of treatment with anti-TNF-agent provided development of clinical remission, decrease and normalization of laboratory tests of disease’s activity, total restoration of joint’s function, increase of quality of life (on 97% in patients with early type, and 72% 0 in ones with late type. The drug was abolished in 39 (39% of patients, 23% — due to the development of secondary inefficiency, and 11% — due to the development of unfavorable effects.Key words: children, early and late rheumatoid arthritis, treatment, infliximab.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(3:30-42

  19. Hearing status in patients with rheumatoid arthritis.

    Science.gov (United States)

    Ahmadzadeh, A; Daraei, M; Jalessi, M; Peyvandi, A A; Amini, E; Ranjbar, L A; Daneshi, A

    2017-10-01

    Rheumatoid arthritis is thought to induce conductive hearing loss and/or sensorineural hearing loss. This study evaluated the function of the middle ear and cochlea, and the related factors. Pure tone audiometry, speech reception thresholds, speech discrimination scores, tympanometry, acoustic reflexes, and distortion product otoacoustic emissions were assessed in rheumatoid arthritis patients and healthy volunteers. Pure tone audiometry results revealed a higher bone conduction threshold in the rheumatoid arthritis group, but there was no significant difference when evaluated according to the sensorineural hearing loss definition. Distortion product otoacoustic emissions related prevalence of conductive or mixed hearing loss, tympanometry values, acoustic reflexes, and speech discrimination scores were not significantly different between the two groups. Sensorineural hearing loss was significantly more prevalent in patients who used azathioprine, cyclosporine and etanercept. Higher bone conduction thresholds in some frequencies were detected in rheumatoid arthritis patients that were not clinically significant. Sensorineural hearing loss is significantly more prevalent in refractory rheumatoid arthritis patients.

  20. Orthopedic Surgery among Patients with Rheumatoid Arthritis: A Population-based study to Identify Risk factors, Sex differences, and Time trends.

    Science.gov (United States)

    Richter, Michael; Crowson, Cynthia S; Matteson, Eric L; Makol, Ashima

    2017-12-20

    To identify risk factors for large joint (LJS) versus small joint surgery (SJS) in rheumatoid arthritis (RA) and evaluate trends in surgery rates over time. A retrospective medical record review was performed of all orthopedic surgeries following first fulfillment of 1987 ACR criteria for adult-onset RA among residents of Olmsted County, Minnesota, USA in 1980-2013. Risk factors were examined using Cox models adjusted for age, sex and calendar year of RA incidence. Trends in incidence of joint surgeries were examined using Poisson regression models. A total of 1077 patients with RA (mean age 56 years, 69% female, 66% seropositive) were followed for a median of 10.7 years during which 112 (90 women) underwent at least one SJS and 204 (141 women) underwent at least one LJS. Risk factors included advanced age, rheumatoid factor and anti-CCP antibody positivity for both SJS and LJS, and BMI≥30 kg/m 2 for LJS. Risk factors for SJS and LJS at any time during follow-up included the presence of radiographic erosions, large joint swelling, and methotrexate use. SJS rates decreased by calendar year of incidence (hazard ratio 0.53; p=0.001), with significant decline in SJS after 1995. The cumulative incidence of SJS was higher in women than men (p=0.008). In recent years, there has been a significant decline in rates of SJS but not LJS in patients with RA. The incidence of SJS is higher among women. Traditional RA risk factors are strong predictors for SJS and LJS. Increasing age and obesity are predictive of LJS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. A variety of human monoclonal antibodies against epidermal growth factor receptor isolated from a phage antibody library.

    Science.gov (United States)

    Kurosawa, Gene; Kondo, Mariko; Kurosawa, Yoshikazu

    2016-11-04

    When the technology for constructing human antibody (Ab) libraries using a phage-display system was developed, many researchers in Ab-related fields anticipated that it would be widely applied to the development of pharmaceutical drugs against various diseases, including cancers. However, successful examples of such applications are very limited. Moreover, researchers who utilize phage-display technology now show divergent ways of thinking about phage Ab libraries. For example, there is debate about what should be the source of V H and V L genes for the construction of libraries to cover the whole repertoire of Abs present in the human body. In the immune system, the introduction of mutations into V genes followed by selection based on binding activity, termed Ab maturation, is required for the production of Abs exhibiting high affinity to the antigen (Ag). Therefore, introduction of mutations and selection are required for isolation of Abs with high affinity after isolation of clones from phage Ab libraries. We constructed a large human Ab library termed AIMS, developed a screening method termed ICOS, and succeeded in isolating many human monoclonal Abs (mAbs) that specifically and strongly bind to various tumor-associated Ags. Eight anti-EGFR mAbs were included, which we characterized. These mAbs showed various different activities against EGFR-expressing cancer cells. In this paper, we describe these data and discuss the possibility and necessity that the mAbs isolated from the AIMS library might be developed as therapeutic drugs against cancers without introduction of mutations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Inhibition of the alternative complement activation pathway in traumatic brain injury by a monoclonal anti-factor B antibody: a randomized placebo-controlled study in mice

    Directory of Open Access Journals (Sweden)

    Holers V Michael

    2007-05-01

    Full Text Available Abstract Background The posttraumatic response to traumatic brain injury (TBI is characterized, in part, by activation of the innate immune response, including the complement system. We have recently shown that mice devoid of a functional alternative pathway of complement activation (factor B-/- mice are protected from complement-mediated neuroinflammation and neuropathology after TBI. In the present study, we extrapolated this knowledge from studies in genetically engineered mice to a pharmacological approach using a monoclonal anti-factor B antibody. This neutralizing antibody represents a specific and potent inhibitor of the alternative complement pathway in mice. Methods A focal trauma was applied to the left hemisphere of C57BL/6 mice (n = 89 using a standardized electric weight-drop model. Animals were randomly assigned to two treatment groups: (1 Systemic injection of 1 mg monoclonal anti-factor B antibody (mAb 1379 in 400 μl phosphate-buffered saline (PBS at 1 hour and 24 hours after trauma; (2 Systemic injection of vehicle only (400 μl PBS, as placebo control, at identical time-points after trauma. Sham-operated and untreated mice served as additional negative controls. Evaluation of neurological scores and analysis of brain tissue specimens and serum samples was performed at defined time-points for up to 1 week. Complement activation in serum was assessed by zymosan assay and by murine C5a ELISA. Brain samples were analyzed by immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL histochemistry, and real-time RT-PCR. Results The mAb 1379 leads to a significant inhibition of alternative pathway complement activity and to significantly attenuated C5a levels in serum, as compared to head-injured placebo-treated control mice. TBI induced histomorphological signs of neuroinflammation and neuronal apoptosis in the injured brain hemisphere of placebo-treated control mice for up to 7 days. In contrast, the

  3. Increased Frequency of Peripheral B and T Cells Expressing Granulocyte Monocyte Colony-Stimulating Factor in Rheumatoid Arthritis Patients

    Directory of Open Access Journals (Sweden)

    Anastasia Makris

    2018-01-01

    Full Text Available ObjectivesGranulocyte monocyte colony-stimulating factor (GM-CSF is currently considered a crucial inflammatory mediator and a novel therapeutic target in rheumatoid arthritis (RA, despite the fact that its precise cellular sources remain uncertain. We studied the expression of GM-CSF in peripheral lymphocytes from RA patients and its change with antirheumatic therapies.MethodsIntracellular GM-CSF expression was assessed by flow cytometry in stimulated peripheral B (CD19+ and T (CD3+ cells from RA patients (n = 40, disease (n = 31 including osteoarthritis n = 15, psoriatic arthritis n = 10, and systemic rheumatic diseases n = 6 and healthy (n = 16 controls. The phenotype of GM-CSF+ B cells was assessed as well as longitudinal changes in GM-CSF+ lymphocytes during methotrexate (MTX, n = 10 or anti-tumor necrosis factor (anti-TNF, n = 10 therapy.ResultsAmong untreated RA patients with active disease (Disease Activity Score 28-C-reactive protein = 5.6 ± 0.89 an expanded population of peripheral GM-CSF+ B (4.1 ± 2.2% and T (3.4 ± 1.6% cells was detected compared with both disease (1.7 ± 0.9%, p < 0.0001 and 1.7 ± 1.3%, p < 0.0001, respectively and healthy (0.3 ± 0.2%, p < 0.0001 and 0.6 ± 0.6%, p < 0.0001 controls. RA GM-CSF+ B cells displayed more commonly a plasmablast or transitional phenotype (37.12 ± 18.34% vs. 14.26 ± 9.46%, p = 0.001 and 30.49 ± 15.04% vs. 2.45 ± 1.84%, p < 0.0001, respectively and less a memory phenotype (21.46 ± 20.71% vs. 66.99 ± 16.63%, p < 0.0001 compared to GM-CSF− cells. GM-CSF expression in RA patients did not correlate to disease duration, activity or serological status. Anti-TNF treatment led to a statistically significant decrease in GM-CSF+ B and T cells while MTX had no significant effect.DiscussionThis is the first study showing an expanded population of GM-CSF+ B and T lymphocytes

  4. Anticardiolipin antibodies in rheumatoid arthritis.

    Science.gov (United States)

    Keane, A; Woods, R; Dowding, V; Roden, D; Barry, C

    1987-10-01

    Anticardiolipin antibody (ACA) was present in the sera of 49% of 90 consecutive patients with rheumatoid arthritis (RA). The ACA was absent in 30 control patients with osteoarthritis. C-reactive protein levels equal to or exceeding 7 mg/dl were found in 10 patients all of whom were ACA positive. ACA was present in a larger proportion of rheumatoid factor (RF) positive than of RF negative patients. Male sex and extra-articular manifestations of RA were both more common in ACA positive than ACA negative patients. In the ACA positive group the lupus anticoagulant and VDRL tests were negative. However, a small number of patients had evidence of vascular events.

  5. Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren’s Syndrome

    Directory of Open Access Journals (Sweden)

    Yu-Ching Lee

    2013-01-01

    Full Text Available We have previously isolated several IgG rheumatoid factors (RFs from patients with both rheumatoid arthritis and idiopathic thrombocytopenia purpura using phage display system. To study IgG RFs in patients with other autoimmune diseases, phage display antibody libraries from a hepatitis C virus infected patient with Sjögren’s syndrome were constructed. After panning, a specific clone RFL11 was isolated for characterization in advance. The binding activity and specificity of RFL11 to IgG Fc fragment were comparable to those of RFs previously isolated. The analysis with existed RF-Fc complex structures indicated the homology model of RFL11 is similar to IgM RF61 complex with high binding affinity of about 6×10-8 M. This effect resulted from longer complementarity-determining region (CDR combining key somatic mutations. In the RFL11-Fc interfaces, the CDR-H3 loop forms a finger-like structure extending into the bottom of Fc pocket and resulting in strong ion and cation-pi interactions. Moreover, a process of antigen-driven maturation was proven by somatically mutated VH residues on H2 and H3 CDR loops in the interfaces. Taken together, these results suggested that high affinity IgG RFs can be generated in patients with Sjögren’s syndrome and may play an important role in the pathogenesis of this autoimmune disease.

  6. Factors that influence fatigue status in patients with severe rheumatoid arthritis (RA) and good disease outcome following 6 months of TNF inhibitor therapy: a comparative analysis.

    LENUS (Irish Health Repository)

    Minnock, Patricia

    2015-11-01

    The objective of the present study is to determine the factors associated with persistent fatigue in patients with severe rheumatoid arthritis (RA) and good disease response to 6 months of tumour necrosis factor inhibitor therapy. Eligible patients with either persistent (PF) or no fatigue (NF) were compared. Using validated questionnaires and bivariate analysis, this cross-sectional survey explored if clinical characteristics, pain, self-efficacy, sleep and mood\\/depression differed between groups. Patients with PF (PF; NF) (n = 28; 28) reported significantly more overall pain (11.3 ± 9.4 (0-33); 6.9 ± 8.9 (0-33)), more recent and current pain intensity (41.4 ± 26.6 (0-80) 24.4 ± 26.6 (0-100) and depression (11.8 ± 7.5 (1-35); 8.2 ± 6.6 (0-26)), than the NF group. There was no significant difference between groups in self-efficacy and both groups experienced poor sleep quality (Pittsburgh Sleep Quality Index >5). Despite having good disease response, the PF group had significantly higher rheumatoid factor incidence, disease activity score-28, early morning stiffness duration and lower incidence of ever-failing disease-modifying anti-rheumatic drugs than the NF group. These findings enhance the fatigue literature in patients with RA prescribed tumour necrosis factor (TNF) inhibition therapy, identifying the potentially modifiable factors of pain and depression, previously demonstrated to be strongly associated with fatigue in non-biologic populations. In addition, this study highlights the association between persistent fatigue and an on-going state of low disease activity. This infers that more judicious disease management could minimise the symptom burden of pain and depression and consequentially fatigue.

  7. Cytotoxic T lymphocyte-Associated Antigen +49G Variant Confers Risk for Anti-CCP- and Rheumatoid Factor-Positive Type of Rheumatoid Arthritis Only in Combination with CT60∗G Allele

    Directory of Open Access Journals (Sweden)

    Bernadett Farago

    2010-01-01

    Full Text Available Controversial observations have been published on the association of the cytotoxic T lymphocyte associated antigen gene's variants with rheumatoid arthritis (RA. After genotyping 428 patients and 230 matched controls, the prevalence of the CT60∗G allele was more frequent in RF- and/or anti-CCP-seropositive RApatients, compared to the healthy controls (P<.001. Regression analysis revealed that the CT60∗G allele is a possible predisposing factor for RA in these subgroups. No accumulation of the +49∗G allele was found among patients, and this variant was not found to correlate with RA. Assaying the possible genotype variations, the +49∗G-CT60∗G allelic combination was accumulated in seropositive RA-subtypes, and was associated with the risk of RA (OR=1.73, P=.001 for the whole RA-population. Although the +49∗G allele did not mean a predisposition to RA alone, in combination with CT60∗G it, also conferred risk, suggesting that the +49A/G variant is associated with the risk of RA only in certain haplotypes.

  8. Diagnostic Delay in Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Mølbaek, Karen; Hørslev-Petersen, Kim; Primdahl, Jette

    2016-01-01

    BACKGROUND: To prevent joint damage among patients with rheumatoid arthritis (RA), there is a need to minimize delays from the onset of symptoms until the initiation of appropriate therapy. The present study explored the factors that have an impact on the time it takes for Danish patients with RA...

  9. Rheumatoid arthritis (image)

    Science.gov (United States)

    Rheumatoid arthritis is an autoimmune disease in which the body's immune system attacks itself. The pattern of joints ... other joints and is worse in the morning. Rheumatoid arthritis is also a systemic disease, involving other body ...

  10. Juvenile rheumatoid arthritis

    Science.gov (United States)

    ... joints. This form of JIA may turn into rheumatoid arthritis. It may involve 5 or more large and ... no known prevention for JIA. Alternative Names Juvenile rheumatoid arthritis (JRA); Juvenile chronic polyarthritis; Still disease; Juvenile spondyloarthritis ...

  11. The reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent does not influence the effect of a second TNF blocking agent in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Blom, Marlies; Kievit, Wietske; Fransen, Jaap; Kuper, Ina H.; den Broeder, Alfons A.; De Gendt, Carla M.A.; Jansen, Tim L.; Brus, Herman L.M.; van de Laar, Mart A.F.J.; van Riel, Piet L.C.M.

    2009-01-01

    OBJECTIVE:To investigate whether the reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent influences the effect of a second TNF blocking agent. METHODS:Data were used from 2 Dutch registries including patients with rheumatoid arthritis (RA) treated with TNF blocking

  12. Golimumab in patients with active rheumatoid arthritis after treatment with tumor necrosis factor a inhibitors: findings with up to five years of treatment in the multicenter, randomized, double-blind, placebo-controlled, phase 3 GO-AFTER study

    NARCIS (Netherlands)

    Smolen, Josef S.; Kay, Jonathan; Doyle, Mittie; Landewé, Robert; Matteson, Eric L.; Gaylis, Norman; Wollenhaupt, Jürgen; Murphy, Frederick T.; Xu, Stephen; Zhou, Yiying; Hsia, Elizabeth C.

    2015-01-01

    Introduction: The aim of this study was to assess long-term golimumab therapy in rheumatoid arthritis (RA) patients who discontinued previous tumor necrosis factor-alpha (TNF)-inhibitor(s). Methods: Patients enrolled into this multicenter, randomized, double-blind, placebo-controlled study of active

  13. Golimumab in patients with active rheumatoid arthritis who have previous experience with tumour necrosis factor inhibitors: results of a long-term extension of the randomised, double-blind, placebo-controlled GO-AFTER study through week 160

    NARCIS (Netherlands)

    Smolen, Josef S.; Kay, Jonathan; Landewé, Robert B. M.; Matteson, Eric L.; Gaylis, Norman; Wollenhaupt, Jurgen; Murphy, Frederick T.; Zhou, Yiying; Hsia, Elizabeth C.; Doyle, Mittie K.

    2012-01-01

    The aim of this study was to assess long-term golimumab therapy in patients with rheumatoid arthritis (RA) who discontinued previous tumour necrosis factor alpha (TNFα) inhibitor(s) for any reason. Results through week 24 of this multicentre, randomised, double-blind, placebo-controlled study of

  14. Insights into the efficacy of golimumab plus methotrexate in patients with active rheumatoid arthritis who discontinued prior anti-tumour necrosis factor therapy: post-hoc analyses from the GO-AFTER study

    NARCIS (Netherlands)

    Smolen, Josef S.; Kay, Jonathan; Matteson, Eric L.; Landewé, Robert; Hsia, Elizabeth C.; Xu, Stephen; Zhou, Yiying; Doyle, Mittie K.

    2014-01-01

    Evaluate golimumab in patients with active rheumatoid arthritis (RA) and previous tumour necrosis factor-α (TNF) inhibitor use. Patients (n=461) previously receiving ≥1 TNF inhibitor were randomised to subcutaneous injections of placebo, golimumab 50 mg or golimumab 100 mg q4 weeks. Primary endpoint

  15. Circulating serum interleukin-6, serum chitinase-3-like protein-1, and plasma vascular endothelial growth factor are not predictive for remission and radiographic progression in patients with early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Brahe, C H; Dehlendorff, C; Østergaard, M

    2018-01-01

    OBJECTIVE: To investigate serum interleukin-6 (IL-6), serum chitinase-3-like protein-1 (YKL-40), and plasma vascular endothelial growth factor (VEGF) as measures of disease activity and predictors of clinical remission and radiographic progression in two early rheumatoid arthritis (RA) randomized...

  16. The reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent does not influence the effect of a second TNF blocking agent in patients with rheumatoid arthritis.

    NARCIS (Netherlands)

    Blom, M.; Kievit, W.; Fransen, J.; Kuper, I.H.; Broeder, A. den; Gendt, C.M. de; Jansen, T.L.Th.A.; Brus, H.L.; Laar, M.A. van der; Riel, P.L.C.M. van

    2009-01-01

    OBJECTIVE: To investigate whether the reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent influences the effect of a second TNF blocking agent. METHODS: Data were used from 2 Dutch registries including patients with rheumatoid arthritis (RA) treated with TNF blocking

  17. Prognosis in monoclonal proteinaemia

    NARCIS (Netherlands)

    Schaar, Cornelis Gerardus

    2006-01-01

    Monoclonal proteinaemia (M-proteinemia) is associated with multiple myeloma (MM) or other hematological malignancies. In the absence of these diseases the term MGUS (Monoclonal Gammopathy of Undetermined Significance) is used. During 1991-1993 1464 patients with newly diagnosed M-proteinemia in the

  18. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  19. Nuclear medicine: Monoclonal antibodies

    International Nuclear Information System (INIS)

    Endo, K.; Sakahara, H.; Koizumi, M.; Kawamura, Y.; Torizuka, K.; Yokoyama, A.

    1986-01-01

    Antitumor monoclonal antibody was successfully labeled with Tc-99m by using dithiosemicarbazone (DTS) as a bifunctional chelating agent. In the first step, DTS was coupled to antibody without loss of immunoreactivity; the compound then efficiently formed a neutral 1:1 chelate with pentavalent or tetravalent Tc-99m. Imaging with Tc-99m-labeled monoclonal antibody to human osteosarcoma (OST-7) clearly displayed a small tumor in nude mice at 6 and 24 hours after intravenous administration. The tumor-to-blood ratio of the Tc-99m-labeled monoclonal antibody was higher than that of a radioiodinated antibody and similar to that of an In-111-labeled antibody. Thus, conjugation of DTS to monoclonal antibody followed by radiometalation is a simple and efficient method of preparing Tc-99m-labeled monoclonal antibody

  20. Development of EMab-51, a Sensitive and Specific Anti-Epidermal Growth Factor Receptor Monoclonal Antibody in Flow Cytometry, Western Blot, and Immunohistochemistry.

    Science.gov (United States)

    Itai, Shunsuke; Kaneko, Mika K; Fujii, Yuki; Yamada, Shinji; Nakamura, Takuro; Yanaka, Miyuki; Saidoh, Noriko; Handa, Saori; Chang, Yao-Wen; Suzuki, Hiroyoshi; Harada, Hiroyuki; Kato, Yukinari

    2017-10-01

    The epidermal growth factor receptor (EGFR) is a member of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases and is involved in cell growth and differentiation. EGFR homodimers or heterodimers with other HER members, such as HER2 and HER3, activate downstream signaling cascades in many cancers. In this study, we developed novel anti-EGFR monoclonal antibodies (mAbs) and characterized their efficacy in flow cytometry, Western blot, and immunohistochemical analyses. First, we expressed the full-length or ectodomain of EGFR in LN229 glioblastoma cells and then immunized mice with LN229/EGFR or ectodomain of EGFR, and performed the first screening using enzyme-linked immunosorbent assays. Subsequently, we selected mAbs according to their efficacy in flow cytometry (second screening), Western blot (third screening), and immunohistochemical (fourth screening) analyses. Among 100 mAbs, only one clone EMab-51 (IgG 1 , kappa) reacted with EGFR in Western blot analysis. Finally, immunohistochemical analyses with EMab-51 showed sensitive and specific reactions against oral cancer cells, warranting the use of EMab-51 to detect EGFR in pathological analyses of EGFR-expressing cancers.

  1. Total shoulder replacement in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Sneppen, O; Fruensgaard, S; Johannsen, Hans Viggo

    1996-01-01

    A prospective study of 62 Neer mark II total shoulder arthroplasties performed during the period from 1981 to 1990 on 51 patients with rheumatoid arthritis was undertaken to evaluate factors associated with component loosening and proximal humeral migration. Thirty-two (51%) showed proximal......, range of movement, abduction force, or function. The risk of clinical asymptomatic loosening is a relatively late complication that is eventually followed by pronounced bone destruction related to the loose component. Long-term radiographic control of total shoulders with rheumatoid arthritis...... is recommended. Hemiarthroplasty with a cemented humeral prosthesis may be a better treatment in the end stage of rheumatoid arthritis of the shoulder....

  2. JUVENILE RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    I N Sartika

    2012-11-01

    Full Text Available Juvenile rheumatoid arthritis (JRA is the most common rheumatic condition in children. JRA is defined as persistent arthritis in 1 or more joints for at least 6 weeks, with the onset before age 16 years. The etiology of JRA is unknown. Antigen activated CD4+ T cell stimulate monocytes, macrophages, and synovial fibroblasts to produce the cytokines Interleukin-1 (IL-1, IL-6, and tumor necrosis factor ? (TNF-? and to secrete matrix metalloproteinases, which lead to chronic inflammation due to infiltration of inflammatory cell, angiogenesis, destruction of cartilage and bone with pannus formation. The 3 major subtypes of JRA are based on the symptoms at disease onset and are designated systemic onset, pauciarticular onset, and polyarticular onset. For all patients, the goals of therapy are to decrease chronic joint pain and suppress the inflammatory process. Poor prognostic have been observed in patients with polyarticular onset, rheumatoid factor, persistent morning stiffness, tenosynovitis, involvement of the small joints, rapid appearance of erosions, active late onset childhood, subcutaneous nodules, or antinuclear antibody.

  3. Smoking and Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Kathleen Chang

    2014-12-01

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease caused by both genetic and environmental factors. Smoking has been implicated as one of the most important extrinsic risk factors for its development and severity. Recent developments have shed light on the pathophysiology of RA in smokers, including oxidative stress, inflammation, autoantibody formation and epigenetic changes. The association of smoking and the development of RA have been demonstrated through epidemiologic studies, as well as through in vivo and animal models of RA. With increased use of biological agents in addition to standard disease-modifying antirheumatic drugs (DMARDs, there has been interest in how smoking affects drug response in RA treatment. Recent evidence suggests the response and drug survival in people treated with anti-tumour necrosis factor (anti-TNF therapy is poorer in heavy smokers, and possible immunological mechanisms for this effect are presented in the current paper.

  4. Generation of a C3c specific monoclonal antibody and assessment of C3c as a putative inflammatory marker derived from complement factor C3

    DEFF Research Database (Denmark)

    Palarasah, Yaseelan; Skjodt, Karsten; Brandt, Jette

    2010-01-01

    complex (C5b-C9) and quantification of complement split products by precipitation-in-gel techniques (e.g. C3d). We have developed a mouse monoclonal antibody (mAb) that is able to detect fluid phase C3c without interference from other products generated from the complement component C3. The C3c specific m....... The C3c mAb was confirmed to be C3c specific, as it showed no cross-reactivity with native (un-cleaved) C3, with C3b, iC3b, or with C3d. Also, no significant reaction was observed with C3 fragments in factor I deficient sera or plasma. This antibody forms the basis for the generation of a robust ELISA...... that allows for a quick and reliable evaluation of complement activation and consumption as a marker for inflammatory processes. We established the C3c plasma range in 100 healthy Danish blood donors with a mean of 3.47 μg/ml and a range of 2.12-4.92 μg/ml. We believe that such an antibody might...

  5. Tumour necrosis factor inhibitors versus combination intensive therapy with conventional disease modifying anti-rheumatic drugs in established rheumatoid arthritis: TACIT non-inferiority randomised controlled trial.

    Science.gov (United States)

    Scott, David L; Ibrahim, Fowzia; Farewell, Vern; O'Keeffe, Aidan G; Walker, David; Kelly, Clive; Birrell, Fraser; Chakravarty, Kuntal; Maddison, Peter; Heslin, Margaret; Patel, Anita; Kingsley, Gabrielle H

    2015-03-13

    To determine whether intensive combinations of synthetic disease modifying drugs can achieve similar clinical benefits at lower costs to high cost biologics such as tumour necrosis factor inhibitors in patients with active rheumatoid arthritis resistant to initial methotrexate and other synthetic disease modifying drugs. Open label pragmatic randomised multicentre two arm non-inferiority trial over 12 months. 24 rheumatology clinics in England. Patients with rheumatoid arthritis who were eligible for treatment with tumour necrosis factor inhibitors according to current English guidance were randomised to either the tumour necrosis factor inhibitor strategy or the combined disease modifying drug strategy. Biologic strategy: start tumour necrosis factor inhibitor; second biologic in six month for non-responders. Alternative strategy: start combination of disease modifying drugs; start tumour necrosis factor inhibitors after six months in non-responders. reduction in disability at 12 months measured with patient recorded heath assessment questionnaire (range 0.00-3.00) with a 0.22 non-inferiority margin for combination treatment versus the biologic strategy. quality of life, joint damage, disease activity, adverse events, and costs. Intention to treat analysis used multiple imputation methods for missing data. 432 patients were screened: 107 were randomised to tumour necrosis factor inhibitors and 101 started taking; 107 were randomised to the combined drug strategy and 104 started taking the drugs. Initial assessments were similar; 16 patients were lost to follow-up (seven with the tumour necrosis factor inhibitor strategy, nine with the combined drug strategy); 42 discontinued the intervention but were followed-up (19 and 23, respectively). The primary outcome showed mean falls in scores on the health assessment questionnaire of -0.30 with the tumour necrosis factor inhibitor strategy and -0.45 with the alternative combined drug strategy. The difference between

  6. Generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound B-cell activating factor

    Directory of Open Access Journals (Sweden)

    Manetta J

    2014-08-01

    Full Text Available Joseph Manetta, Holly Bina, Paul Ryan, Niles Fox, Derrick R Witcher, Kristine Kikly Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Abstract: B-cell activating factor (BAFF is a B-cell survival factor with a key role in B-cell homeostasis and tolerance. Dysregulated BAFF expression may contribute to autoimmune diseases or B-cell malignancies via effects on abnormal B-lymphocyte activation, proliferation, survival, and immunoglobulin secretion. Monoclonal antibodies were generated against human BAFF, characterized for species specificity and affinity, and screened for the ability to neutralize both membrane-bound and soluble BAFF. In addition, studies were undertaken to determine the relative potency of membrane-bound and soluble BAFF. Tabalumab has a high affinity for human, cynomolgus monkey, and rabbit BAFF. No binding to mouse BAFF was detected. Tabalumab was able to neutralize soluble human, cynomolgus monkey, or rabbit BAFF with equal potency. Our data demonstrate that membrane-bound BAFF can be a more potent stimulus for B-cells than soluble BAFF, and tabalumab also neutralized membrane-bound BAFF. Tabalumab prevented BAFF from binding to BAFF receptors and demonstrated pharmacodynamic effects in human BAFF transgenic mice. Tabalumab is a high-affinity human antibody with neutralizing activity against membrane-bound and soluble BAFF. Given our findings that membrane-bound BAFF can have greater in vitro potency than soluble BAFF, neutralization of both forms of BAFF is likely to be important for optimal therapeutic effect. Keywords: autoimmunity, B-cell malignancies, B-cell survival factor, BAFF

  7. Life stories of people with rheumatoid arthritis who retired early: how gender and other contextual factors shaped their everyday activities, including paid work.

    Science.gov (United States)

    Stamm, T A; Machold, K P; Smolen, J; Prodinger, B

    2010-06-01

    The aim of the present study was to explore how contextual factors affect the everyday activities of women and men with rheumatoid arthritis (RA), as evident in their life stories. Fifteen people with RA, who had retired early due to the disease, were interviewed up to three times, according to a narrative biographic interview style. The life stories of the participants, which were reconstructed from the biographical data and from the transcribed 'told story' were analysed from the perspective of contextual factors, including personal and environmental factors. The rigour and accuracy of the analysis were enhanced by reflexivity and peer-review of the results. The life stories of the participants in this study reflected how contextual factors (such as gender, the healthcare system, the support of families and social and cultural values) shaped their everyday activities. In a society such as in Austria, which is based on traditional patriarchal values, men were presented with difficulties in developing a non-paid-work-related role. For women, if paid work had to be given up, they were more likely to engage in alternative challenging activities which enabled them to develop reflective skills, which in turn contributed to a positive and enriching perspective on their life stories. Health professionals may thus use some of the women's strategies to help men. Interventions by health professionals in people with RA may benefit from an approach sensitive to personal and environmental factors.

  8. Rheumatoid factor testing in Spanish primary care: A population-based cohort study including 4.8 million subjects and almost half a million measurements.

    Science.gov (United States)

    Morsley, Klara; Miller, Anne; Luqmani, Raashid; Fina-Aviles, Francesc; Javaid, Muhammad Kassim; Edwards, Christopher J; Pinedo-Villanueva, Rafael; Medina, Manuel; Calero, Sebastian; Cooper, Cyrus; Arden, Nigel; Prieto-Alhambra, Daniel

    2018-02-26

    Rheumatoid factor (RF) testing is used in primary care in the diagnosis of rheumatoid arthritis (RA); however a positive RF may occur without RA. Incorrect use of RF testing may lead to increased costs and delayed diagnoses. The aim was to assess the performance of RF as a test for RA and to estimate the costs associated with its use in a primary care setting. A retrospective cohort study using the Information System for the Development of Research in Primary Care database (contains primary care records and laboratory results of >80% of the Catalonian population, Spain). Participants were patients ≥18 years with ≥1 RF test performed between 01/01/2006 and 31/12/2011, without a pre-existing diagnosis of RA. Outcome measures were an incident diagnosis of RA within 1 year of testing, and the cost of testing per case of RA. 495,434/4,796,498 (10.3%) patients were tested at least once. 107,362 (21.7%) of those tested were sero-positive of which 2768 (2.6%) were diagnosed with RA within 1 year as were 1141/388,072 (0.3%) sero-negative participants. The sensitivity of RF was 70.8% (95% CI 69.4-72.2), specificity 78.7% (78.6-78.8), and positive and negative predictive values 2.6% (2.5-2.7) and 99.7% (99.6-99.7) respectively. Approximately €3,963,472 was spent, with a cost of €1432 per true positive case. Although 10% of patients were tested for RF, most did not have RA. Limiting testing to patients with a higher pre-test probability would significantly reduce the cost of testing. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  9. Evaluation of rheumatoid factor and anti-citrullinated peptide antibodies in relation to rheumatological manifestations in patients with leprosy from Southern Brazil.

    Science.gov (United States)

    Dionello, Carla Fontoura; Rosa Utiyama, Shirley Ramos; Radominski, Sebastião Cézar; Stahlke, Ewalda; Stinghen, Servio Tulio; de Messias-Reason, Iara Jose

    2016-10-01

    Leprosy patients may present several osteoarticular complaints, which require further evaluation of inflammatory diseases, such as rheumatoid arthritis (RA). Therefore, an adequate clinical assessment in addition to testing for rheumatoid factors (RF) and anticyclic citrullinated peptide antibodies (anti-CCP), can be useful in order to establish the correct diagnosis. In this study, the relation of RF and anti-CCP with rheumatological manifestations was evaluated in 97 leprosy patients from Southern Brazil. The results were compared to RA patients and healthy controls from the same geographical area and ethnic background. Neuropathy was observed in 71.1% and arthritis in 35.1% of the leprosy patients. A high frequency of RF positivity was observed among the leprosy patients (41.2%, 40/97), with RF immunoglobulin A (IgA) significantly associated with arthritis (OR = 7.9, 95% CI = 1.5-40.6 P = 0.008). Anti-CCP was observed in 9.3% (9/97) of the patients, with anti-CCP2 being the most frequent subtype. Only 4.1% (4/97) of the patients were RF and anti-CCP concomitantly positive. RF IgM showed a significant association with leprosy when compared to healthy controls (P leprosy in patients from the same geographical area and ethnic background (anti-CCP2 OR = 38.6; 95% CI = 16.49-90.26; P leprosy with other inflammatory diseases, such as RA, clinical and laboratorial evaluation of affected patients must be carefully assessed in order to achieve proper diagnosis and treatment. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  10. The role of anti-cyclic citrullinated peptide antibodies in predicting rheumatoid arthritis.

    Science.gov (United States)

    Rexhepi, Sylejman; Rexhepi, Mjellma; Sahatçiu-Meka, Vjollca; Tafaj, Argjend; Izairi, Remzi; Rexhepi, Blerta

    2011-01-01

    The study presents the results of predicting role of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis, compared to rheumatoid factor. 32 patients with rheumatoid arthritis were identified from a retrospective chart review. The results of our study show that presence of the rheumatoid factor has less diagnostic and prognostic significance than the anti-cyclic citrullinated peptide, and suggests its superiority in predicting an erosive disease course.

  11. Rheumatoid arthritis associated interstitial lung disease: a review

    Directory of Open Access Journals (Sweden)

    Deborah Assayag

    2014-04-01

    Full Text Available Rheumatoid arthritis is a common inflammatory disease affecting about 1% of the population. Interstitial lung disease is a serious and frequent complication of rheumatoid arthritis. Rheumatoid arthritis associated interstitial lung disease (RA-ILD is characterized by several histopathologic subtypes. This article reviews the proposed pathogenesis and risk factors for RA-ILD. We also outline the important steps involved in the work-up of RA-ILD and review the evidence for treatment and prognosis.

  12. Rheumatoid Arthritis Educational Video Series

    Science.gov (United States)

    ... Corner / Patient Webcasts / Rheumatoid Arthritis Educational Video Series Rheumatoid Arthritis Educational Video Series This series of five videos ... Your Arthritis Managing Chronic Pain and Depression in Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of Life ...

  13. Genetics Home Reference: rheumatoid arthritis

    Science.gov (United States)

    ... Share: Email Facebook Twitter Home Health Conditions Rheumatoid arthritis Rheumatoid arthritis Printable PDF Open All Close All Enable ... in my area? Other Names for This Condition arthritis, rheumatoid RA Related Information How are genetic conditions and ...

  14. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Rheumatoid Arthritis (RA). You will learn how the diagnosis of RA is made, what happens to your ... Link Below To Play Rheumatoid Arthritis: Symptoms and Diagnosis Rheumatoid Arthritis: What is Happening to the Joints? ...

  15. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Happening to the Joints? Rheumatoid Arthritis: Gaining Control – Working with your Rheumatologist Rheumatoid Arthritis: Additional Conditions Rheumatoid Arthritis: The Immune System Don’t have ...

  16. A post-marketing safety and efficacy assessment of a monoclonal antibody purified high-purity factor VIII concentrate.

    Science.gov (United States)

    Hay, C R; Lee, C A; Savidge, G

    1996-01-01

    The identification of infrequent side-effects of clotting factor concentrates, undetected by clinical trials, is facilitated by post-marketing surveillance. We present a post-marketing surveillance study in which 97 patients with haemophilia A, attending three haemophilia centres, were treated over a median follow-up period of 284 days (range 1-1074), and a total follow-up period of 30,080 days, with a pasteurized immunoaffinity purified factor VIII concentrate (Monoclate-P, Armour, Collegeville, USA). 5216 infusions, using 10,527,000 units of Monoclate-P, were carried out, mostly for routine haemarthroses or prophylaxis. No new inhibitors were observed during the study. At the start of the study 60/97 were HIV seropositive, 67/97 HBs antibody positive, 12 HbsAb negative and the remainder HBsAb positive before the study period. 13/14 tested were HAV seropositive at the beginning of the study. One patient became HAV seropositive during the study period, an infection thought to be community acquired. No other seroconversions were observed. Only one mild transfusion reaction was observed. This study confirms the safety and efficacy of Monoclate-P. Post-marketing surveillance or nationally organized pharmaco-vigilance should be practiced more widely to enable identification of low-frequency side-effects of treatment.

  17. Management of osteoporosis in rheumatoid arthritis patients.

    Science.gov (United States)

    Hoes, Jos N; Bultink, Irene E M; Lems, Willem F

    2015-03-01

    In rheumatoid arthritis (RA) patients, the risk of both vertebral and non-vertebral fractures is roughly doubled, which is for an important part caused by inflammation-mediated amplification of bone loss and by immobilization. New treatments have become available in the last two decades to treat both RA and osteoporosis. Epidemiology and assessment of osteoporosis and fracture risk (including the influence of RA disease activity and bone-influencing medications such as glucocorticoids), the importance of vertebral fracture assessment in addition to bone density measurement in patients with RA, the use of disease-modifying antirheumatic drugs and their effects on generalized bone loss, and current and possible future anti-osteoporotic pharmacotherapeutic options are discussed with special focus on RA. Assessment of osteoporosis in RA patients should include evaluation of the effects of disease activity and bone-influencing medications such as (the dose of) glucocorticoids, above standard risk factors for fractures or osteoporosis as defined by the FRAX instrument. Disease-modifying antirheumatic drugs are now well able to control disease activity using treat to target strategies. This lowering of disease activity by antirheumatic medications such as anti-TNF-α results in hampering of generalized bone loss; however, no fracture data are currently available. When treating osteoporosis in RA patients, additional focus should be on calcium supplementation, particularly in glucocorticoid users, and also on sufficient vitamin D use. Several anti-osteoporotic medications are now on the market; oral bisphosphonates are most commonly used, but in recent years, more agents have entered the market such as the parenteral antiresorptives denosumab (twice yearly) and zoledronic acid (once yearly), and the anabolic agent parathyroid hormone analogues. New agents, such as odanacatib and monoclonal antibodies against sclerostin, are now being tested and will most likely enlarge the

  18. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available Appointments • Support Our Research Arthritis Information Disease Information Rheumatoid Arthritis Psoriatic Arthritis Ankylosing Spondylitis Osteoarthritis Gout Lyme Disease Osteoporosis News Rheumatoid Arthritis News ...

  19. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of Life Rehabilitation Management for Rheumatoid Arthritis Patients Rehabilitation of Older Adult ...

  20. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Depression in Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of Life Rehabilitation Management for Rheumatoid Arthritis Patients Rehabilitation of Older Adult ...

  1. Incidence rate of falls and its risk factors in patients with rheumatoid arthritis compared to controls: Four years of the TOMORROW study.

    Science.gov (United States)

    Mamoto, Kenji; Inui, Kentaro; Okano, Tadashi; Sugioka, Yuko; Tada, Masahiro; Koike, Tatsuya; Nakamura, Hiroaki

    2017-01-01

    Patients with rheumatoid arthritis (RA) have been recognized to experience falls frequently due to functional disabilities. The aim of this study was to prospectively investigate factors influencing falls in patients with RA compared to controls. We compared the frequency of falls in 208 RA patients and 205 age- and sex-matched volunteers for four years and analyzed risk factors for falls in RA patients using multivariate regression analysis. No significant difference in the incidence rate of falls (/person-year) between patients with RA (median [interquartile range]: 0 [0, 0.5]) and controls (0 [0, 0.5]) was evident during four years. Logistic regression analysis identified age, sex, body mass index, history of falls, and lower limb implant at baseline as significant risk factors for falls. The highest quartile of anti-CCP antibody level (>300.6 U/ml) was the strongest predictor for multiple falls (odds ratio, 2.97; 95% confidence interval, 1.12-7.91, p = 0.029) among RA patients. During four years we could not observe the higher incidence rate of falls in RA patients compared to controls in our cohort. Subjects with a higher titer of anti-CCP antibody might be at higher risk of frequent falls among RA patients.

  2. Nature of the bifunctional chelating agent used for radioimmunotherapy with yttrium-88 monoclonal antibodies: critical factors in determining in vivo survival and organ toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kozak, R.W.; Raubitschek, A.; Mirzadeh, S.; Brechbiel, M.W.; Junghaus, R.; Gansow, O.A.; Waldmann, T.A. (Center for Biologics Evaluation and Research, FDA, Bethesda, MD (USA))

    1989-05-15

    One factor that is critical to the potential effectiveness of radioimmunotherapy is the design of radiometal-chelated antibodies that will be stable in vivo. Stability in vivo depends on the condition that both the chelate linkage and radiolabeling procedures not alter antibody specificity and biodistribution. In addition, synthesis and selection of the chelating agent is critical for each radiometal in order to prevent inappropriate release of the radiometal in vivo. In the present study, we compare the in vivo stability of seven radioimmunoconjugates that use different polyaminocarboxylate chelating agents to complex yttrium-88 to the mouse anti-human interleukin-2 receptor monoclonal antibody, anti-Tac. Chelate linkage and radiolabeling procedures did not alter the immunospecificity of anti-Tac. In order to assess whether yttrium was inappropriately released from the chelate-coupled antibody in vivo, iodine-131-labeled and yttrium-88 chelate-coupled antibodies were simultaneously administered to the same animals to correlate the decline in yttrium and radioiodinated antibody activity. The four stable yttrium-88 chelate-coupled antibodies studied displayed similar iodine-131 and yttrium-88 activity, indicating minimal elution of yttrium-88 from the complex. In contrast, the unstable yttrium-88 chelate-coupled antibodies had serum yttrium-88 activities that declined much more rapidly than their iodine-131 activities, suggesting loss of the radiolabel yttrium-88 from the chelate. Furthermore, high rates of yttrium-88 elution correlated with deposition in bone. Four chelating agents emerged as promising immunotherapeutic reagents: isothiocyanate benzyl DTPA and its derivatives 1B3M, MX, and 1M3B.

  3. Establishment of EMab-134, a Sensitive and Specific Anti-Epidermal Growth Factor Receptor Monoclonal Antibody for Detecting Squamous Cell Carcinoma Cells of the Oral Cavity.

    Science.gov (United States)

    Itai, Shunsuke; Yamada, Shinji; Kaneko, Mika K; Chang, Yao-Wen; Harada, Hiroyuki; Kato, Yukinari

    2017-12-01

    Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, activates downstream signaling cascades in many tumors. In this study, we established novel anti-EGFR monoclonal antibodies (mAbs) and characterized their efficacy in flow cytometry, Western blot, and immunohistochemical analyses. We immunized mice with a combination of the extracellular domain of EGFR and EGFR-overexpressing LN229 glioblastoma cells (LN229/EGFR) and performed the first screening using enzyme-linked immunosorbent assay. Next, we selected mAbs using flow cytometry. Among 156 established clones, two mAbs, EMab-51 (IgG 1 , kappa) and EMab-134 (IgG 1 , kappa), reacted with EGFR in Western blot analysis; EMab-134 showed a much higher sensitivity compared with EMab-51. We compared the binding affinities of EMab-51 and EMab-134 using flow cytometry; the calculated K D values for EMab-51 and EMab-134 against SAS cells/HSC-2 cells were 9.2 × 10 -9 M/9.9 × 10 -9 M and 2.6 × 10 -9 M/8.3 × 10 -9 M, respectively, indicating that EMab-134 has a higher affinity to EGFR-expressing cells. Immunohistochemical analysis of EMab-51 and EMab-134 showed sensitive and specific reactions against oral cancer cells; EMab-134 demonstrated a much higher sensitivity (36/38 cases; 94.7%) to oral squamous cell carcinomas compared with EMab-51 (6/38 cases; 15.8%). This novel anti-EGFR mAb, EMab-134, could be advantageous for detecting EGFR in the pathological analysis of EGFR-expressing cancers.

  4. Pharmacokinetics, biodistribution and dosimetry of {sup 99m}Tc-labeled anti-human epidermal growth factor receptor humanized monoclonal antibody R3 in rats

    Energy Technology Data Exchange (ETDEWEB)

    Escobar, Normando Iznaga; Morales, Alejo Morales; Duconge, Jorge; Torres, Idania Caballero; Fernandez, Eduardo; Gomez, Jose A

    1998-01-01

    The pharmacokinetics, biodistribution and dosimetry of {sup 99m}Tc-labeled anti-human epidermal growth factor receptor (anti-hEGF-r) humanized monoclonal antibody (MAb) R3 was investigated following intravenous injection in normal Wistar rats. Serum disappearance curves were best fit by a two-compartment model having a mean distribution half-life (t{sub (1(2{alpha}}{sub ))}) of 0.250 h and a mean elimination (t{sub (1(2{beta}}{sub ))}) of 13.89 h. Among the various organs, a little accumulation of the radiolabeled antibody was found only in kidneys. Biodistribution and dosimetry studies in humans were performed by extrapolation of the animal data to humans. Absorbed dose to normal organs and the remainder of the whole body were estimated using the medical internal radiation dose formula, and dose contributions from radioactivity in transit through the gastrointestinal tract were estimated using a compartment model. Extrapolated values of radiation absorbed dose to normal organs in rads per millicurie administered were whole body, 0.0085; lower large intestine wall, 0.0898; small intestine, 0.0530; upper large intestine wall, 0.0731; and kidneys, 0.0455. The effective dose equivalent predicted was 0.0162 rem/mCi and the effective dose was found to be 0.015 rem/mCi. On the basis of the pharmacokinetics, biodistribution and internal radiation dosimetry information obtained in this study, a diagnostic phase I clinical trial with {sup 99m}Tc-labeled humanized MAb R3 conjugate in patients should be supported.

  5. Pharmacokinetics, biodistribution and dosimetry of 99mTc-labeled anti-human epidermal growth factor receptor humanized monoclonal antibody R3 in rats

    International Nuclear Information System (INIS)

    Escobar, Normando Iznaga; Morales, Alejo Morales; Duconge, Jorge; Torres, Idania Caballero; Fernandez, Eduardo; Gomez, Jose A.

    1998-01-01

    The pharmacokinetics, biodistribution and dosimetry of 99m Tc-labeled anti-human epidermal growth factor receptor (anti-hEGF-r) humanized monoclonal antibody (MAb) R3 was investigated following intravenous injection in normal Wistar rats. Serum disappearance curves were best fit by a two-compartment model having a mean distribution half-life (t (1(2α)) ) of 0.250 h and a mean elimination (t (1(2β)) ) of 13.89 h. Among the various organs, a little accumulation of the radiolabeled antibody was found only in kidneys. Biodistribution and dosimetry studies in humans were performed by extrapolation of the animal data to humans. Absorbed dose to normal organs and the remainder of the whole body were estimated using the medical internal radiation dose formula, and dose contributions from radioactivity in transit through the gastrointestinal tract were estimated using a compartment model. Extrapolated values of radiation absorbed dose to normal organs in rads per millicurie administered were whole body, 0.0085; lower large intestine wall, 0.0898; small intestine, 0.0530; upper large intestine wall, 0.0731; and kidneys, 0.0455. The effective dose equivalent predicted was 0.0162 rem/mCi and the effective dose was found to be 0.015 rem/mCi. On the basis of the pharmacokinetics, biodistribution and internal radiation dosimetry information obtained in this study, a diagnostic phase I clinical trial with 99m Tc-labeled humanized MAb R3 conjugate in patients should be supported

  6. Effectiveness of a web-based personalized rheumatoid arthritis risk tool with or without a health educator for knowledge of RA risk factors.

    Science.gov (United States)

    Prado, Maria G; Iversen, Maura D; Yu, Zhi; Miller Kroouze, Rachel; Triedman, Nellie A; Kalia, Sarah S; Lu, Bing; Green, Robert C; Karlson, Elizabeth W; Sparks, Jeffrey A

    2018-01-05

    To assess knowledge of rheumatoid arthritis (RA) risk factors among unaffected first-degree relatives (FDRs) and to study whether a personalized RA education tool increases risk factor knowledge. We performed a randomized controlled trial assessing RA educational interventions among 238 FDRs. The web-based Personalized Risk Estimator for RA (PRE-RA) tool displayed personalized RA risk results (genetics, autoantibodies, demographics, and behaviors) and educated about risk factors. Subjects were randomly assigned to: Comparison arm (standard RA education, n=80), PRE-RA arm (PRE-RA alone, n=78), or PRE-RA Plus arm (PRE-RA and a one-on-one session with a trained health educator, n=80). The RA Knowledge Score (RAKS, the number of 8 established RA risk factors identified as related to RA) was calculated at baseline and post-education (immediate/6 weeks/6 months/12 months). We compared RAKS and its components at each post-education point by randomization arm. At baseline before education, few FDRs identified behavioral RA risk factors (15.9% for dental health, 31.9% for smoking, 47.5% for overweight/obesity, and 54.2% for diet). After education, RAKS increased in all arms, higher in PRE-RA and PRE-RA Plus than Comparison at all post-education points (peducation (proportion agreeing smoking is a risk factor at 6 weeks: 83.1% in PRE-RA Plus arm, 71.8% in PRE-RA, and 43.1% in Comparison arms, peducation tool successfully increased RA risk factor knowledge. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Emerging immunotherapies for rheumatoid arthritis

    Science.gov (United States)

    Reynolds, Gary; Cooles, Faye AH; Isaacs, John D; Hilkens, Catharien MU

    2014-01-01

    Novel treatments in development for rheumatoid arthritis target 3 broad areas: cytokines, cells, and signaling pathways. Therapies from each domain share common advantages (for example previously demonstrated efficacy, potential long-term immunomodulation, and oral administration respectively) that have stimulated research in each area but also common obstacles to their development. In this review recent progress in each area will be discussed alongside the factors that have impeded their path to clinical use. PMID:24535556

  8. [Bone structure in rheumatoid arthritis].

    Science.gov (United States)

    Ono, Kumiko; Ohashi, Satoru; Tanaka, Sakae; Matsumoto, Takuya

    2013-07-01

    In rheumatoid arthritis (RA) , the osteoclast pathway is activated by abnormal immune conditions accompanied by chronic inflammation, resulting in periarticular osteoporosis and local bone destruction around joints. In addition, multiple factors, including reduced physical activity and pharmacotherapies such as steroids, lead to systemic osteoporosis. These conditions cause decreasing bone mineral density and deterioration of bone quality, and expose patients to increased risk of fracture. Understanding the bone structures of RA and evaluating fracture risk are central to the treatment of RA.

  9. LDL cholesterolemia as a novel risk factor for radiographic progression of rheumatoid arthritis: a single-center prospective study.

    Directory of Open Access Journals (Sweden)

    Yune-Jung Park

    Full Text Available Dyslipidemia has been implicated in various musculoskeletal diseases, including rheumatoid arthritis (RA. Evidence is emerging that there might be a pathogenic interaction among inflammation, dyslipidemia, and adipokines. We prospectively investigated the association of cumulative lipid levels with radiographic progression of RA. RA patients (n=242 underwent plasma cholesterol assessment at four visits. Disease activity parameters and X-rays of the hands and feet were also serially monitored in these patients. The cumulative inflammatory burden and lipid levels were estimated by time-integrated values. Serum leptin and adiponectin concentrations were determined by ELISA. When patients were divided into three groups according to time-integrated lipid levels, as expected, patients with LDL cholesterol and/or triglyceride levels in the third tertile had persistently higher ESR and CRP levels. In parallel, a more rapid radiographic progression over two years was observed in patients with higher LDL cholesterol and/or triglyceride levels. In multivariate analysis, time-integrated LDL cholesterol was independently associated with radiographic progression. Particularly, the risk of radiographic progression was 5.6-fold in a subgroup with both LDL cholesterol and triglyceride levels in the third tertile. Moreover, LDL cholesterol synergistically increased the adjusted probability of radiographic progression in patients with high serum leptin levels but not in those without. These results demonstrate that LDL cholesterolemia is a novel serum marker that can be used to predict radiographic progression of RA, which seems to be related to circulatory leptin levels. We suggest that personalized and more aggressive anti-rheumatic therapy is required for dyslipidemic subgroups in RA patients.

  10. Socioeconomic and therapy factor influence on self-reported fatigue, anxiety and depression in rheumatoid arthritis patients

    Directory of Open Access Journals (Sweden)

    Mirjana Lapčević

    Full Text Available Abstract Introduction: Fatigue, anxiety and depression are very frequent symptoms in patients with rheumatoid arthritis (RA. Goals: In this study we evaluated the influence of socioeconomic characteristics, therapy and comorbidities on the self-reported high fatigue, anxiety and depression in patients with RA. Method: Multicenter cross-sectional study was performed in 22 health institutions in Serbia during the period from April-August 2014 in population of older RA patients. Self-reported patients health status was measured by: Fatigue Assessment Scale, Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Treatment modalities were defined as: (1 non-steroidal anti-inflammatory drugs (NSAIDs and/or analgesics and/or corticosteroids; (2 synthetic disease-modifying antirheumatic drugs (DMARDs alone or in combination with corticosteroids and/or NSAIDs and (3 any RA treatment which includes biologic DMARDs. Results: There were significant predictors of high depression: synthetic DMARDs therapy in combination with corticosteroids and/or NSAIDs, physiotherapist self-payment, frequent taxi use, alternative treatment and employment status. The need for another person's assistance, supplemental calcium therapy and professional qualifications were the predictors of a high fatigue, whereas the age above 65 years had the protective effect on it. Anxiety was an independent high fatigue predictor. The predictors of a high anxiety were: gastroprotection with proton-pump inhibitors and patient occupation. Conclusion Socioeconomic predictors of self-reported high depression, anxiety or fatigue are different for each of the mentioned outcomes, while accompanied with the basic RA treatment they exclusively explain a high depression. The anxiety, jointed with the socioeconomic variables and supplemental therapy, is a significant fatigue predictor in RA patients.

  11. Disclosure of Personalized Rheumatoid Arthritis Risk Using Genetics, Biomarkers, and Lifestyle Factors to Motivate Health Behavior Improvements: A Randomized Controlled Trial.

    Science.gov (United States)

    Sparks, Jeffrey A; Iversen, Maura D; Yu, Zhi; Triedman, Nellie A; Prado, Maria G; Miller Kroouze, Rachel; Kalia, Sarah S; Atkinson, Michael L; Mody, Elinor A; Helfgott, Simon M; Todd, Derrick J; Dellaripa, Paul F; Bermas, Bonnie L; Costenbader, Karen H; Deane, Kevin D; Lu, Bing; Green, Robert C; Karlson, Elizabeth W

    2017-10-12

    To determine the effect of disclosure of rheumatoid arthritis (RA) risk personalized with genetics, biomarkers, and lifestyle factors on health behavior intentions. We performed a randomized controlled trial among first-degree relatives without RA. Subjects assigned to the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) group received the web-based PRE-RA tool for RA risk factor education and disclosure of personalized RA risk estimates, including genotype/autoantibody results and behaviors (n = 158). Subjects assigned to the comparison arm received standard RA education (n = 80). The primary outcome was readiness for change based on the trans-theoretical model, using validated contemplation ladder scales. Increased motivation to improve RA risk-related behaviors (smoking, diet, exercise, or dental hygiene) was defined as an increase in any ladder score compared to baseline, assessed immediately, 6 weeks, and 6 months post-intervention. Subjects reported behavior change at each visit. We performed intent-to-treat analyses using generalized estimating equations for the binary outcome. Subjects randomized to PRE-RA were more likely to increase ladder scores over post-intervention assessments (relative risk 1.23, 95% confidence interval [95% CI] 1.01, 1.51) than those randomized to nonpersonalized education. At 6 months, 63.9% of PRE-RA subjects and 50.0% of comparison subjects increased motivation to improve behaviors (age-adjusted difference 15.8%; 95% CI 2.8%, 28.8%). Compared to nonpersonalized education, more PRE-RA subjects increased fish intake (45.0% versus 22.1%; P = 0.005), brushed more frequently (40.7% versus 22.9%; P = 0.01), flossed more frequently (55.7% versus 34.8%; P = 0.004), and quit smoking (62.5% versus 0.0% among 11 smokers; P = 0.18). Disclosure of RA risk personalized with genotype/biomarker results and behaviors increased motivation to improve RA risk-related behaviors. Personalized medicine approaches may motivate health

  12. Link between rheumatoid arthritis and chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Tomasz Kaczyński

    2018-03-01

    Full Text Available Chronic periodontitis is an infectious disease associated with the progressive destruction of periodontal tissues. In recent years, more and more data indicate an existing relationship between periodontal disease and rheumatoid arthritis. The link between both diseases has been confirmed in multiple studies. Despite the fact that this association might be based on shared environmental and genetic risk factors, a possible causal relation was advocated by experimental, epidemiological and interventional studies, with the leading role of Porphyromonas gingivalis. Individuals with chronic periodontitis are at an increased risk of developing rheumatoid arthritis, as well as rheumatoid arthritis patients are at an increased risk of chronic periodontitis and more severe forms of periodontitis. Furthermore, there is a correlation between the activity in both diseases – patients with more severe periodontitis suffer from more active rheumatoid arthritis. Intervention attempts were also performed, which demonstrated that eliminating periodontal infection and inflammation can affect the severity of rheumatoid arthritis. In this paper, we review the current knowledge about the link between both diseases, focusing on its clinical implications. Will periodontal treatment become a part of standard therapy for rheumatoid arthritis?

  13. Why golimumab in the treatment of psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis?

    Directory of Open Access Journals (Sweden)

    M. Rossini

    2015-03-01

    Full Text Available Golimumab is an anti-TNF monoclonal antibody administred subcutaneously once a month and produced with an innovative technology that minimizes immunogenicity. This paper reviews and updates the main studies on the efficacy, safety and pharmacoeconomic aspects of treatment with golimumab of psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis.

  14. Monoclonal antibodies in oncology

    International Nuclear Information System (INIS)

    Chan, S.Y.T.; Sikora, K.

    1986-01-01

    Monoclonal antibodies (MCAs) can be used to differentiate between normal and neoplastic cells and thus exploited for diagnostic and, ultimately, therapeutic gain. The evidence for the existence of human tumour antigens is reviewed. Several areas of diagnosis are already benefiting from the application of the monoclonal technology. Immunohistology can help the pathologist with difficult diagnostic problems. New classifications of lymphoma and leukaemia can be based on specific surface molecules. Similarly, the detection of shed tumour antigens is already established as part of the routine assessment of many patients with common solid tumours. Isotopically labeled monoclonal antibodies have been used to localise primary and metastatic tumours. The use of antibodies in this way is not only a promising diagnostic tool but also the first step in studying the possibility of arming antibodies to provide therapeutic agents. Such trials are currently in progress. (Auth.)

  15. Location of Primary Tumor and Benefit From Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies in Patients With RAS and BRAF Wild-Type Metastatic Colorectal Cancer

    Science.gov (United States)

    Moretto, Roberto; Cremolini, Chiara; Rossini, Daniele; Pietrantonio, Filippo; Battaglin, Francesca; Mennitto, Alessia; Bergamo, Francesca; Loupakis, Fotios; Marmorino, Federica; Berenato, Rosa; Marsico, Valentina Angela; Caporale, Marta; Antoniotti, Carlotta; Masi, Gianluca; Salvatore, Lisa; Borelli, Beatrice; Fontanini, Gabriella; Lonardi, Sara; De Braud, Filippo

    2016-01-01

    Introduction. Right- and left-sided colorectal cancers (CRCs) differ in clinical and molecular characteristics. Some retrospective analyses suggested that patients with right-sided tumors derive less benefit from anti-epidermal growth factor receptor (EGFR) antibodies; however, molecular selection in those studies was not extensive. Patients and Methods. Patients with RAS and BRAF wild-type metastatic CRC (mCRC) who were treated with single-agent anti-EGFRs or with cetuximab-irinotecan (if refractory to previous irinotecan) were included in the study. Differences in outcome between patients with right- and left-sided tumors were investigated. Results. Of 75 patients, 14 and 61 had right- and left-sided tumors, respectively. None of the right-sided tumors responded according to RECIST, compared with 24 left-sided tumors (overall response rate: 0% vs. 41%; p = .0032), and only 2 patients with right-sided tumors (15%) versus 47 patients with left-sided tumors (80%) achieved disease control (p < .0001). The median duration of progression-free survival was 2.3 and 6.6 months in patients with right-sided and left-sided tumors, respectively (hazard ratio: 3.97; 95% confidence interval: 2.09–7.53; p < .0001). Conclusion. Patients with right-sided RAS and BRAF wild-type mCRC seemed to derive no benefit from single-agent anti-EGFRs. Implications for Practice: Right- and left-sided colorectal tumors have peculiar epidemiological and clinicopathological characteristics, distinct gene expression profiles and genetic alterations, and different prognoses. This study assessed the potential predictive impact of primary tumor site with regard to anti-epidermal growth factor receptor (EGFR) monoclonal antibody treatment in patients with RAS and BRAF wild-type metastatic colorectal cancer. The results demonstrated the lack of activity of anti-EGFRs in RAS and BRAF wild-type, right-sided tumors, thus suggesting a potential role for primary tumor location in driving treatment choices

  16. Fasinumab (REGN475, an antinerve growth factor monoclonal antibody, for the treatment of acute sciatic pain: results of a proof-of-concept study

    Directory of Open Access Journals (Sweden)

    Tiseo PJ

    2014-08-01

    .9%, and 64.8% in the placebo, fasinumab 0.1mg/kg, and fasinumab 0.3 mg/kg groups, respectively. The most commonly reported TEAEs included paresthesia, arthralgia, pain in extremity, and headache. Conclusion: Administration of fasinumab provided no significant clinical benefit compared with placebo for the pain or functional limitations associated with acute sciatica. Fasinumab was generally well tolerated and incidence of TEAEs appeared to be dose related. Keywords: fasinumab, monoclonal antibody, nerve growth factor, sciatica, lumbar radiculopathy

  17. Tyrosine kinases in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kobayashi Akiko

    2011-08-01

    Full Text Available Abstract Rheumatoid arthritis (RA is an inflammatory, polyarticular joint disease. A number of cellular responses are involved in the pathogenesis of rheumatoid arthritis, including activation of inflammatory cells and cytokine expression. The cellular responses involved in each of these processes depends on the specific signaling pathways that are activated; many of which include protein tyrosine kinases. These pathways include the mitogen-activated protein kinase pathway, Janus kinases/signal transducers and activators transcription pathway, spleen tyrosine kinase signaling, and the nuclear factor κ-light-chain-enhancer of activated B cells pathway. Many drugs are in development to target tyrosine kinases for the treatment of RA. Based on the number of recently published studies, this manuscript reviews the role of tyrosine kinases in the pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic strategies of RA.

  18. High titer of anti-citrullinated peptide antibody is a risk factor for severe carotid atherosclerotic plaque in patients with rheumatoid arthritis: the TOMORROW study.

    Science.gov (United States)

    Okano, Tadashi; Inui, Kentaro; Sugioka, Yuko; Sugioka, Kenichi; Matsumura, Yoshiki; Takahashi, Shinji; Tada, Masahiro; Mamoto, Kenji; Wakitani, Shigeyuki; Koike, Tatsuya; Nakamura, Hiroaki

    2017-08-01

    Cardiovascular disease is one of the complications of rheumatoid arthritis (RA). We researched the morbidity and severity of existing carotid atherosclerosis plaque and associated risk factors in patients with RA. This study included 413 participants, including 208 patients with RA and 205 age- and sex-matched healthy volunteers. Carotid ultrasound, clinical data collection and assessment of cardiovascular risk factors were performed. Atherosclerotic plaque was defined as an intima-media thickness ≥ 1.1 mm. Severity of plaque was assessed by plaque score, defined as the sum of the maximal thickness of all plaques in bilateral carotid arteries. Data were analyzed from 200 patients with RA and 202 controls. Carotid plaque was observed more frequently in patients with RA than controls (47.0 vs. 36.1%, P = 0.027). Moreover, plaque score was significantly higher in RA patients (P = 0.032). In logistic regression analysis, RA represented an independent risk factor for the presence of plaque (adjusted odds ratio, 1.68; 95% confidence interval, 1.03-2.74). Comparing RA patients with and without plaque, anti-cyclic citrullinated peptide (anti-CCP) antibodies titer was significantly higher in patients with plaque (315.8 ± 454.1 U/mL) than in patients without (165.7 ± 281.1 U/mL; P = 0.005). Moreover, multiple linear regression analysis clarified that anti-CCP antibody titer was associated with plaque score in patients with RA. High prevalence of any carotid plaques and severe carotid plaques were more frequent in patients with RA. High titer of anti-CCP antibodies represented a risk factor for severe carotid atherosclerotic plaque in patients with RA. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  19. Juvenile rheumatoid arthritis

    International Nuclear Information System (INIS)

    Naz, S.; Mushtaq, A.; Bari, A.; Maqsud, A.; Khan, M. Z.; Ahmad, T. M.; Saira Rehman

    2013-01-01

    Objective: To determine the spectrum of clinical presentation, laboratory parameters and drug therapy in patients with Juvenile Rheumatoid Arthritis (JRA). Study Design: Case series. Place and Duration of Study: The Children's Hospital and The Institute of Child Health, Lahore, from October 2008 to October 2011. Methodology: All patients who fulfilled the American College of Rheumatology criteria for JRA were enrolled. Their clinical features, investigations done and treatment received for JRA were noted. Statistical analysis of data was done on SPSS version 16.0 for obtaining descriptive statistics. Results: Out of 185 patients, 50.3% (n = 93) were females; 54% (n = 100) were between 10 - 15 years of age. Polyarthritis was found in 71.9% (n = 133) followed by oligoarthritis (22.7%, n = 42) and systemic onset disease (5.4%, n = 10). Morning stiffness (78%) and fever (68%) were the most common clinical presentations. All patients with systemic onset disease had fever (n = 10) followed by skin rash, hepatosplenomegaly and lymphadenopathy. Uveitis was found in 2 patients, and both belonged to the oligoarticular group. Rheumatoid factor was found in 10.27% (n = 19) of all patients. All patients were given non-steroidal anti-inflammatory drugs (NSAIDs). Disease modifying agents (methotrexate) were given to 43.8% (n = 81). Steroids were used in 61% (n = 113) of patients either with NSAIDs alone or NSAIDs plus methotrexate. Conclusion: Disease profile of JRA at the study centre showed that polyarthritis is the commonest type. Recognition of subtypes will help in planning the management of these patients. (author)

  20. Single Cell Chemical Cytometry of Akt Activity in Rheumatoid Arthritis and Normal Fibroblast-like Synoviocytes in Response to Tumor Necrosis Factor α.

    Science.gov (United States)

    Mainz, Emilie R; Serafin, D Stephen; Nguyen, Tuong T; Tarrant, Teresa K; Sims, Christopher E; Allbritton, Nancy L

    2016-08-02

    The etiology of rheumatoid arthritis (RA) is poorly understood, and 30% of patients are unresponsive to established treatments targeting tumor necrosis factor α (TNFα). Akt kinase is implicated in TNFα signaling and may act as a barometer of patient responses to biologic therapies. Fluorescent peptide sensors and chemical cytometry were employed to directly measure Akt activity as well as proteolytic activity in individual fibroblast-like synoviocytes (FLS) from RA and normal subjects. The specificity of the peptide reporter was evaluated and shown to be a valid measure of Akt activity in single cells. The effect of TNFα treatment on Akt activity was highly heterogeneous between normal and RA subjects, which was not observable in bulk analyses. In 2 RA subjects, a bimodal distribution of Akt activity was observed, primarily due to a subpopulation (21.7%: RA Subject 5; 23.8%: RA Subject 6) of cells in which >60% of the reporter was phosphorylated. These subjects also possessed statistically elevated proteolytic cleavage of the reporter relative to normal subjects, suggesting heterogeneity in Akt and protease activity that may play a role in the RA-affected joint. We expect that chemical cytometry studies pairing peptide reporters with capillary electrophoresis will provide valuable data regarding aberrant kinase activity from small samples of clinical interest.

  1. Long-term survival of subcutaneous anti-tumor necrosis factor biological drugs administered between 2008 and 2012 in a cohort of rheumatoid arthritis patients.

    Science.gov (United States)

    Alvarez Rivas, Noelia; Vazquez Rodriguez, Tomas R; Miranda Filloy, Jose A; Garcia-Porrua, Carlos; Sanchez-Andrade Fernández, Amalia

    2017-05-25

    To compare the survival of subcutaneous anti-tumor necrosis factor (TNF) drugs used between 2008 and 2012 prescribed in accordance with clinical practice. Retrospective, observational study of the patients in our center diagnosed with rheumatoid arthritis (RA). We included patients who had received a subcutaneous anti-TNF agent for at least 6 months. The data were analyzed using the SPSS V17.0 statistical package. Forty-nine RA patients started subcutaneous biological treatment with an anti-TNF agent (32 with etanercept and 17 with adalimumab). The mean age was 45.94 years (75.5% female). The mean disease duration prior to starting anti-TNF administration was 2.67 years. The mean age at the start of treatment was 51.84 years, and the average Disease Activity Score 28 was 4.93. The median survival of the anti-TNF treatment was 8.40 years; the survival of etanercept was the longer of the two. The main reason for discontinuation was secondary failure (90.9%). In routine clinical practice, the survival of subcutaneous anti-TNF treatment was extensive and was independent of whether or not the patients received concomitant immunosuppressive therapy. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  2. Use of anti-tumor necrosis factor biologics in the treatment of rheumatoid arthritis does not change human T-lymphotropic virus type 1 markers: a case series.

    Science.gov (United States)

    Umekita, Kunihiko; Umeki, Kazumi; Miyauchi, Shunichi; Ueno, Shiro; Kubo, Kazuyoshi; Kusumoto, Norio; Takajo, Ichiro; Nagatomo, Yasuhiro; Okayama, Akihiko

    2015-09-01

    Anti-tumor necrosis factor (anti-TNF) biologics are effective in the treatment of rheumatoid arthritis (RA); however, it is still not clear whether this treatment promotes the development of malignancies such as lymphoma. Human T-lymphotropic virus type 1 (HTLV-1), which is a causative agent of adult T-cell lymphoma (ATL), is prevalent in Japan. Many HTLV-1-positive patients with RA are assumed to exist; however, there have thus far been no reports on the effect of anti-TNF biologics on HTLV-1-positive patients. We analyzed the response to treatment with anti-TNF biologics and change of HTLV-1 markers in two cases of RA. The two cases showed no response based on the European League Against of Rheumatism response criteria 60-96 weeks after administration of anti-TNF biologics (infliximab and etanercept). No signs of ATL were observed and HTLV-1 markers, such as proviral load and clonality of HTLV-1-infected cells, showed no significant change in either of two cases. Therefore, treatment with anti-TNF biologics did not induce activation of HTLV-1, although the effect on RA was not as effective as in HTLV-1-negative patients in this limited study. Further long-term study with a greater number of patients is necessary to clarify the safety and efficacy of anti-TNF biologics in HTLV-1-positive patients with RA.

  3. Pro region engineering of nerve growth factor by deep mutational scanning enables a yeast platform for conformational epitope mapping of anti-NGF monoclonal antibodies.

    Science.gov (United States)

    Medina-Cucurella, Angélica V; Zhu, Yaqi; Bowen, Scott J; Bergeron, Lisa M; Whitehead, Timothy A

    2018-04-12

    Nerve growth factor (NGF) plays a central role in multiple chronic pain conditions. As such, anti-NGF monoclonal antibodies (mAbs) that function by antagonizing NGF downstream signaling are leading drug candidates for non-opioid pain relief. To evaluate anti-canine NGF (cNGF) mAbs we sought a yeast surface display platform of cNGF. Both mature cNGF and pro-cNGF displayed on the yeast surface but bound conformationally sensitive mAbs at most 2.5-fold in mean fluorescence intensity above background, suggesting that cNGF was mostly misfolded. To improve the amount of folded, displayed cNGF, we used comprehensive mutagenesis, FACS, and deep sequencing to identify point mutants in the pro-region of canine NGF that properly enhance the folded protein displayed on the yeast surface. Out of 1,737 tested single point mutants in the pro region, 49 increased the amount of NGF recognized by conformationally sensitive mAbs. These gain-of-function mutations cluster around residues A-61-P-26. Gain-of-function mutants were additive, and a construct containing three mutations increased amount of folded cNGF to 23- fold above background. Using this new cNGF construct, fine conformational epitopes for tanezumab and three anti-cNGF mAbs were evaluated. The epitope revealed by the yeast experiments largely overlapped with the tanezumab epitope previously determined by X-ray crystallography. The other mAbs showed site-specific differences with tanezumab. As the number of binding epitopes of functionally neutralizing anti-NGF mAbs on NGF are limited, subtle differences in the individual interacting residues on NGF that bind each mAb contribute to the understanding of each antibody and variations in its neutralizing activity. These results demonstrate the potential of deep sequencing-guided protein engineering to improve the production of folded surface-displayed protein, and the resulting cNGF construct provides a platform to map conformational epitopes for other anti-neurotrophin m

  4. Monoclonal antibodies in myeloma

    DEFF Research Database (Denmark)

    Sondergeld, P.; van de Donk, N. W. C. J.; Richardson, P. G.

    2015-01-01

    The development of monoclonal antibodies (mAbs) for the treatment of disease goes back to the vision of Paul Ehrlich in the late 19th century; however, the first successful treatment with a mAb was not until 1982, in a lymphoma patient. In multiple myeloma, mAbs are a very recent and exciting add...

  5. Transforming growth factor (TGF)-β signalling is increased in rheumatoid synovium but TGF-β blockade does not modify experimental arthritis.

    Science.gov (United States)

    Gonzalo-Gil, E; Criado, G; Santiago, B; Dotor, J; Pablos, J L; Galindo, M

    2013-11-01

    The aim of this study was to analyse the distribution of regulatory and inhibitory mothers against decapentaplegic homologue (Smad) proteins as markers of active transforming growth factor (TGF)-β signalling in rheumatoid arthritis (RA) synovial tissue and to investigate the effect of TGF-β blockade in the development and progression of collagen-induced arthritis. The expression of Smad proteins in synovial tissues from RA, osteoarthritic and healthy controls was analysed by immunohistochemistry. Arthritis was induced in DBA/1 mice by immunization with chicken type-II collagen (CII). TGF-β was blocked in vivo with the specific peptide p17 starting at the time of immunization or on the day of arthritis onset. T cell population frequencies and specific responses to CII were analysed. The expression of cytokines and transcription factors was quantified in spleen and joint samples. Statistical differences between groups were compared using the Mann-Whitney U-test or one-way analysis of variance (anova) using the Kruskal-Wallis test. p-Smad-2/3 and inhibitory Smad-7 expression were detected in RA and control tissues. In RA, most lymphoid infiltrating cells showed nuclear p-Smad-2/3 without Smad-7 expression. Treatment with TGF-β antagonist did not affect clinical severity, joint inflammation and cartilage damage in collagen-induced arthritis. Frequency of T cell subsets, mRNA levels of cytokines and transcription factors, specific proliferation to CII, serum interleukin (IL)-6 and anti-CII antibodies were comparable in p17 and phosphate-buffered saline (PBS)-treated groups. The pattern of Smad proteins expression demonstrates active TGF-β signalling in RA synovium. However, specific TGF-β blockade does not have a significant effect in the mice model of collagen-induced arthritis. © 2013 British Society for Immunology.

  6. Rheumatoid cachexia revisited: a metabolic co-morbidity in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kayo eMasuko

    2014-11-01

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease in which pro-inflammatory cytokines, including tumor necrosis factor (TNF-alpha, play a crucial role. The chronic inflammation, combined with reduced physical activity, leads to muscle wasting whereas fat mass would be maintained; the resulting abnormal metabolic state is described as rheumatoid cachexia. Since the loss of muscle volume would be compensated by the increased fat mass, body mass index (BMI is reported not to reflect the nutritional status in RA patients. The implication of rheumatoid cachexia for cardiovascular risk and clinical prognosis is not clearly understood, however, adequate control of disease activity in combination with appropriate physical exercise could be the most important strategy to control rheumatoid cachexia and related metabolic problems.

  7. Infusion Reactions Associated with the Medical Application of Monoclonal Antibodies: The Role of Complement Activation and Possibility of Inhibition by Factor H

    OpenAIRE

    Tamás Fülöp; Tamás Mészáros; Gergely Tibor Kozma; János Szebeni; Mihály Józsi

    2018-01-01

    Human application of monoclonal antibodies (mAbs), enzymes, as well as contrast media and many other particulate drugs and agents referred to as “nanomedicines”, can initiate pseudoallergic hypersensitivity reactions, also known as infusion reactions. These may in part be mediated by the activation of the complement system, a major humoral defense system of innate immunity. In this review, we provide a brief outline of complement activation-related pseudoallergy (CARPA) in general, and then f...

  8. Rheumatoid arthritis and bacterial infections

    Directory of Open Access Journals (Sweden)

    N L Prokopjeva

    2008-01-01

    Full Text Available To study features of bacterial infections course in pts with rheumatoid arthritis (RA and changes of laboratory measures after focus of infection sanation. Material and methods. 46 pts with definite rheumatoid arthritis were examined at the time of comorbid infection (Cl detection and after infection focus sanation. Bacteriological test with evaluation of flora sensitivity to antibiotics by disco-diffusion method was performed at baseline and after the course of antibacterial therapy to assess its efficacy. Hemogram, serum fibrinogen, rheumatoid factor, circulating immune complexes (CIC, C-reactive protein levels were assessed. Serum interleukin (IL 1(3, IL6 and neopterin concentrations were examined by immune-enzyme assay in a part of pts. Typical clinical features of Cl were present in only 28 (60,9% pts. 13 (28,3% pts had fever, 12 (26,0% — leukocytosis, 15 (32,6% — changes of leucocyte populations. Some laboratory measures (thrombocytes, fibrinogen, CIC, neopterin levels significantly decreased (p<0,05 after infection focus sanation without correction of disease modifying therapy. Cl quite often develop as asymptomatic processes most often in pts with high activity and can induce disturbances promoting appearance of endothelial dysfunction, atherothrombosis and reduction of life duration. So timely detection and proper sanation of infection focuses should be performed in pts with RA

  9. Rheumatoid Arthritis: Can It Affect the Lungs?

    Science.gov (United States)

    Rheumatoid arthritis: Can it affect the lungs? Can rheumatoid arthritis affect your lungs? Answers from April Chang-Miller, ... know. Arthritis Foundation. http://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/articles/lung-disease-rheumatoid-arthritis.php. Accessed ...

  10. Association of Cardiovascular Risk Factors with Carotid Intima Media Thickness in Patients with Rheumatoid Arthritis with Low Disease Activity Compared to Controls: A Cross-Sectional Study.

    Directory of Open Access Journals (Sweden)

    Deborah F van Breukelen-van der Stoep

    Full Text Available Rheumatoid arthritis (RA has been identified as an independent cardiovascular risk factor. The importance of risk factors such as hypertension and hyperlipidemia in the generation of atherosclerosis in RA patients is unclear. This study analyzed clinical parameters associated with carotid intima media thickness (cIMT in patients with RA.Subjects with RA and healthy controls without RA, both without known cardiovascular disease, were included. Participants underwent a standard physical examination and laboratory measurements including a lipid profile. cIMT was measured semi-automatically by ultrasound.In total 243 RA patients and 117 controls were included. The median RA disease duration was 7 years (IQR 2-14 years. The median DAS28 was 2.4 (IQR 1.6-3.2 and 114 (50.4% of the RA patients were in remission. The presence of RA and cIMT were not associated (univariate analysis. Multivariable regression analysis showed that cIMT in RA patients was associated with age (B = 0.006, P<0.001 and systolic blood pressure (B = 0.003, P = 0.003. In controls, cIMT was associated with age (B = 0.006, P<0.001 and smoking (B = 0.097, P = 0.001.cIMT values were similar between RA patients and controls. Hypertension was strongly associated with cIMT in RA patients. After adjustment, no association between cIMT and specific RA disease characteristics was found in this well treated RA cohort.

  11. COMORBIDITY IN RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    T. A. Panafidina

    2014-01-01

    Full Text Available The peak onset of rheumatoid arthritis (RA is at 30-55 years of age. At this age, the patients have also other concomi- tant diseases (comorbidities that affect the course and prognosis of RA, the choice of its treatment policy, quality of life of the patients. Objective: to identify the most important and common comorbidities in patients with RA. Subjects and methods. Two hundred patients (median age 55 [46; 61] years were enrolled; there was a preponderance of women (82.5% with median disease duration 5 [1; 10] years, seropositive for IgM rheumatoid factor (83.0% and anti-cyclic citrullinated peptide antibodies (81.6% with moderate and high disease activity (median DAS28 value 3.9 [3.1; 4.9]. Varying degrees of destructive changes in hand and foot joints were radiologically detected in 71.2% of the patients; 64.5% of the patients had Functional Class II. Methotrexate was given to 69.5% of the patients; therapy with biological agents was used in 21.0% of the cases. 15.5% of the patients did not receive DMARD or biologics. 43.0% of the patients with RA received glucocorticoids. Results. Comorbidities were present in 72.0% of the patients with RA. The most common diseases were hypertension (60.0%, dyslipidemia (45.0%, fractures at various sites (29.5%, and coronary heart disease (21.0%. Myocardial infarction and stroke were observed in 1.5 and 1.0% of cases, respectively. There was diabetes mellitus (DM in 7.5% of the cases and osteoporosis in 15.5% of the patients. 81.7% of the patients with RA and hypertension and 80.0% of those with RA and DM received antihypertensive and sugar-lowering therapy, respectively. At the same time the RA patients with dyslipidemia and osteoporosis received specific drugs far less frequently (30.0 and 29.0%, respectively. Conclusion. Comorbidities are frequently encountered in RA. By taking into account the fact that cardiovascular dis- eases are a main cause of death in RA; it is necessary to adequately and timely

  12. Individualized monitoring of drug bioavailability and immunogenicity in rheumatoid arthritis patients treated with the tumor necrosis factor alpha inhibitor infliximab

    DEFF Research Database (Denmark)

    Bendtzen, Klaus; Geborek, Pierre; Svenson, Morten

    2006-01-01

    Infliximab, an anti-tumor necrosis factor alpha (anti-TNFalpha) antibody, is effective in the treatment of several immunoinflammatory diseases. However, many patients experience primary or secondary response failure, suggesting that individualization of treatment regimens may be beneficial...

  13. Contribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoter.

    Science.gov (United States)

    Fonseca, João Eurico; Cavaleiro, João; Teles, José; Sousa, Elsa; Andreozzi, Valeska L; Antunes, Marília; Amaral-Turkman, Maria A; Canhão, Helena; Mourão, Ana F; Lopes, Joana; Caetano-Lopes, Joana; Weinmann, Pamela; Sobral, Marta; Nero, Patrícia; Saavedra, Maria J; Malcata, Armando; Cruz, Margarida; Melo, Rui; Braña, Araceli; Miranda, Luis; Patto, José V; Barcelos, Anabela; da Silva, José Canas; Santos, Luís M; Figueiredo, Guilherme; Rodrigues, Mário; Jesus, Herberto; Quintal, Alberto; Carvalho, Teresa; da Silva, José A Pereira; Branco, Jaime; Queiroz, Mário Viana

    2007-01-01

    The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-alpha) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-alpha gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-alpha promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.

  14. Effect of Anticitrullinated Protein Antibody Status on Response to Abatacept or Antitumor Necrosis Factor-α Therapy in Patients with Rheumatoid Arthritis: A US National Observational Study.

    Science.gov (United States)

    Harrold, Leslie R; Litman, Heather J; Connolly, Sean E; Kelly, Sheila; Hua, Winnie; Alemao, Evo; Rosenblatt, Lisa; Rebello, Sabrina; Kremer, Joel M

    2018-01-01

    Assess whether baseline anticyclic citrullinated peptide antibodies (anti-CCP) status is associated with treatment response in patients with rheumatoid arthritis (RA) initiating abatacept (ABA) or a tumor necrosis factor-α inhibitor (TNFi). Using the Corrona RA registry, patients were identified who initiated ABA or a TNFi (June 2004-January 2015), had a followup visit 6 months (± 3 mos) after initiation, and anti-CCP measured at or prior to initiation. Primary outcome was mean change in Clinical Disease Activity Index (CDAI) from initiation to 6 months. Treatment response was evaluated based on a typical patient profile (female, aged 57 yrs, body mass index of 30 kg/m 2 , baseline CDAI of 20, 1 prior biologic, and no comorbidities other than RA). Secondary outcomes included remission and low disease activity. There were 566 ABA initiators [anti-CCP+ (≥ 20 units/ml): n = 362; anti-CCP- (< 20 units/ml): n = 204] and 1715 TNFi initiators (anti-CCP+: n = 1113; anti-CCP-: n = 602). Differences between treatment groups included baseline disease duration, CDAI, and prior biologic use. At 6 months, anti-CCP+ ABA initiators were associated with significantly greater CDAI response versus anti-CCP- ABA initiators; no significant difference was observed for TNFi initiators. When considering a typical RA patient profile, CDAI response was greater in anti-CCP+ versus anti-CCP- ABA initiators; anti-CCP+ versus anti-CCP- TNFi initiators were similar. Secondary outcome responses were also greater in anti-CCP+ versus anti-CCP- ABA initiators; TNFi initiators did not differ by anti-CCP status. In a US-based clinical practice setting, anti-CCP status was associated with a differential treatment response to ABA, but not TNFi.

  15. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.

    Science.gov (United States)

    Gómez-Reino, Juan J; Carmona, Loreto; Valverde, Vicente Rodríguez; Mola, Emilio Martín; Montero, Maria Dolores

    2003-08-01

    The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.

  16. Predictors of Flare Following Etanercept Withdrawal in Patients with Rheumatoid Factor-negative Juvenile Idiopathic Arthritis Who Reached Remission while Taking Medication.

    Science.gov (United States)

    Aquilani, Angela; Pires Marafon, Denise; Marasco, Emiliano; Nicolai, Rebecca; Messia, Virginia; Perfetti, Francesca; Magni-Manzoni, Silvia; De Benedetti, Fabrizio

    2018-05-01

    To evaluate the rate of flare after etanercept (ETN) withdrawal in patients with juvenile idiopathic arthritis (JIA) who attained clinical remission while taking medication, and to identify predictors of flare. Patients were included with oligo- (oJIA) and rheumatoid factor-negative polyarticular JIA (pJIA) who received a first course of ETN for at least 18 months, maintained clinically inactive disease (CID) for at least 6 months during treatment, and were followed for 12 months after ETN withdrawal. Demographic and clinical features were collected at onset, at baseline (initiation of ETN), and at time of disease flare. After ETN withdrawal, 66 of the 110 patients enrolled (60%) flared with arthritis (of whom 7 flared with concurrent anterior uveitis; none with uveitis alone). The median time to flare was 4.3 months (interquartile range 2.5-6.4) with no evident differences between oJIA and pJIA. The number and type of joints involved at baseline and characteristics of ETN treatment/discontinuation were not associated with flare. Patients who flared were more frequently males (p = 0.034), positive for antinuclear antibody (ANA; p = 0.047), and had higher values of C-reactive protein (CRP; p = 0.012) at baseline. These variables remained significantly associated with flare in a multivariate logistic analysis, a model accounting for only 14% of the variability of the occurrence of the flare. Our results show that a significant proportion of patients with JIA who maintain CID for at least 6 months experience a relapse after ETN withdrawal. Male sex, presence of ANA, and elevated CRP at baseline were associated with higher risk of flare.

  17. Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis—a proof of principle and exploratory trial: is dose tapering practical in good responders?

    Science.gov (United States)

    Lorente-Cánovas, Beatriz; Doré, Caroline J; Bosworth, Ailsa; Ma, Margaret H; Galloway, James B; Cope, Andrew P; Pande, Ira; Walker, David; Scott, David L

    2017-01-01

    Abstract Objectives RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response. Methods We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0–6) patients were randomized to control (constant TNFi) or two experimental groups (tapering TNFi by 33 or 66%). Subsequently (months 6–12) control subjects were randomized to taper TNFi by 33 or 66%. Disease flares (DAS28 increasing ⩾0.6 with at least one additional swollen joint) were the primary outcome. Results Two hundred and forty-four patients were screened, 103 randomized and 97 treated. In months 0–6 there were 8/50 (16%) flares in controls, 3/26 (12%) with 33% tapering and 6/21 (29%) with 66% tapering. Multivariate Cox analysis showed time to flare was unchanged with 33% tapering but was reduced with 66% tapering compared with controls (adjusted hazard ratio 2.81, 95% CI: 0.99, 7.94; P = 0.051). Analysing all tapered patients after controls were re-randomized (months 6–12) showed differences between groups: there were 6/48 (13%) flares with 33% tapering and 14/39 (36%) with 66% tapering. Multivariate Cox analysis showed 66% tapering reduced time to flare (adjusted hazard ratio 3.47, 95% CI: 1.26, 9.58; P = 0.016). Conclusion Tapering TNFi by 33% has no impact on disease flares and appears practical in patients in sustained remission and low disease activity states. Trail registration EudraCT, https://www.clinicaltrialsregister.eu, 2010-020738-24; ISRCTN registry, https://www.isrctn.com, 28955701 PMID:28968858

  18. Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis-a proof of principle and exploratory trial: is dose tapering practical in good responders?

    Science.gov (United States)

    Ibrahim, Fowzia; Lorente-Cánovas, Beatriz; Doré, Caroline J; Bosworth, Ailsa; Ma, Margaret H; Galloway, James B; Cope, Andrew P; Pande, Ira; Walker, David; Scott, David L

    2017-11-01

    RA patients receiving TNF inhibitors (TNFi) usually maintain their initial doses. The aim of the Optimizing Treatment with Tumour Necrosis Factor Inhibitors in Rheumatoid Arthritis trial was to evaluate whether tapering TNFi doses causes loss of clinical response. We enrolled RA patients receiving etanercept or adalimumab and a DMARD with DAS28 under 3.2 for over 3 months. Initially (months 0-6) patients were randomized to control (constant TNFi) or two experimental groups (tapering TNFi by 33 or 66%). Subsequently (months 6-12) control subjects were randomized to taper TNFi by 33 or 66%. Disease flares (DAS28 increasing ⩾0.6 with at least one additional swollen joint) were the primary outcome. Two hundred and forty-four patients were screened, 103 randomized and 97 treated. In months 0-6 there were 8/50 (16%) flares in controls, 3/26 (12%) with 33% tapering and 6/21 (29%) with 66% tapering. Multivariate Cox analysis showed time to flare was unchanged with 33% tapering but was reduced with 66% tapering compared with controls (adjusted hazard ratio 2.81, 95% CI: 0.99, 7.94; P = 0.051). Analysing all tapered patients after controls were re-randomized (months 6-12) showed differences between groups: there were 6/48 (13%) flares with 33% tapering and 14/39 (36%) with 66% tapering. Multivariate Cox analysis showed 66% tapering reduced time to flare (adjusted hazard ratio 3.47, 95% CI: 1.26, 9.58; P = 0.016). Tapering TNFi by 33% has no impact on disease flares and appears practical in patients in sustained remission and low disease activity states. EudraCT, https://www.clinicaltrialsregister.eu, 2010-020738-24; ISRCTN registry, https://www.isrctn.com, 28955701. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  19. Use of exploratory factor analysis to ascertain the correlation between the activities of rheumatoid arthritis and infection by human parvovirus B19.

    Science.gov (United States)

    Kakurina, Natalja; Kadisa, Anda; Lejnieks, Aivars; Mikazane, Helena; Kozireva, Svetlana; Murovska, Modra

    2015-01-01

    We evaluated a possible correlation between the clinical activities of rheumatoid arthritis (RA) and human parvovirus B19 (B19) infection using exploratory factor analysis (EFA). RA patients were organized into two groups: 100 patients in the main group and 97 in the RA(DAS28) group. Four subgroups were defined from the main group according to the presence or absence of certain infection-specific markers: group I comprised 43 patients who had IgG antibodies against B19; group II, 25 patients with active B19 infection (B19-specific IgM antibodies and/or plasma viremia); group III, 19 patients with latent/persistent B19 infection (virus-specific sequences in peripheral blood leukocytes' DNA with or without B19-specific IgG antibodies), and group IV, 13 patients without infection markers. The RA(DAS28) group was divided into four subgroups similarly to the main group: group I, 35; group II, 31; group III, 19; and group IV, 12 patients. Disease-specific clinical values in both groups were analyzed employing EFA, and the RA(DAS28) group was additionally assessed using Disease Activity Score (DAS)28. RA activity was higher in patients who had markers of B19 infection. The highest activity of RA in both study groups was in patients with latent/persistent infection. In the RA(DAS28) group, according to DAS28, the highest activity of RA was in patients with active B19 infection. Using EFA and DAS28, a correlation between the clinical activity of RA and B19 infection was confirmed. These data suggest that EFA is applicable for medico-biological studies. Copyright © 2015 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  20. Influence of route of administration/drug formulation and other factors on adherence to treatment in rheumatoid arthritis (pain related) and dyslipidemia (non-pain related).

    Science.gov (United States)

    Fautrel, Bruno; Balsa, Alejandro; Van Riel, Piet; Casillas, Marta; Capron, Jean-Philippe; Cueille, Carine; de la Torre, Inmaculada

    2017-07-01

    A comprehensive review was performed to investigate the effect of route of administration on medication adherence and persistence in rheumatoid arthritis (RA) and to compare adherence/persistence with oral medications between RA and a non-painful disease (dyslipidemia). Comprehensive database searches were performed to identify studies investigating medication adherence and/or persistence in adults with RA receiving conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidemia receiving statins. Studies had to be published after 1998 in English and involve ≥6 months' follow up. Adherence and persistence were compared between the different routes of drug administration in RA, and between the two diseases for oral medications. A total of 35 and 28 papers underwent data extraction for RA and dyslipidemia, respectively. Within the constraints of the analysis, adherence and persistence rates appeared broadly similar for the different routes of drug administration in RA. Adherence to oral medications was also broadly similar across the two diseases, but persistence was lower in dyslipidemia. Poor adherence has clinical consequences in both diseases: greater disease activity and risk of flare in RA, and increased serum cholesterol levels and risk of heart and cerebrovascular disease in dyslipidemia. Over 1-3 years, poor adherence to biologic RA medications led to increased resource use and medical costs but lower total direct costs due to reduced biologic drug costs. Conversely, poor adherence to dyslipidemia medications resulted in increased total direct costs. In both diseases, adherence improved with patient education/support. The route of drug administration and the symptomatic (pain) nature of the disease do not appear to be dominant factors for drug adherence or persistence in RA. The wide range of adherence and persistence values and definitions across studies made comparisons between drug formulations and

  1. Monoclonal antibody 6E4 against human GAPDHS protein

    Czech Academy of Sciences Publication Activity Database

    Dorosh, Andriy

    2011-01-01

    Roč. 30, č. 3 (2011), s. 321-321 ISSN 1554-0014 Institutional research plan: CEZ:AV0Z50520701 Keywords : Monoclonal antibody * GAPDHS Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.417, year: 2011

  2. Connective tissue markers of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Møller, H J

    1998-01-01

    Rheumatoid arthritis (RA) is a common systemic autoimmune disorder of unknown aetiology. The most common outcome of RA is a progressive development of joint destruction and deformity. Early introduction of disease-modifying antirheumatic drugs seems important for prevention of the long term...... of rheumatoid factor contributes to the classification of arthritis as RA, and acute phase reactants are useful for quantifying and comparing the level of inflammatory activity in the course of a given patient. There is, however, a lack of sensitive and specific biochemical markers for RA, and frontline...

  3. Sleep Disturbances in Patients with Rheumatoid Arthritis | Abbasi ...

    African Journals Online (AJOL)

    Sleep Disturbances in Patients with Rheumatoid Arthritis. ... that insomnia, pain and disease intensity were the most important factors that ... that sleep disturbances are frequent in patients with RA and may contribute to disease severity.

  4. Adherence to methotrexate in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Bliddal, Henning; Eriksen, Stine A; Christensen, Robin

    2015-01-01

    Objectives. To study adherence to methotrexate (MTX) and factors of importance thereof in patients with rheumatoid arthritis (RA). Methods. Patients with a hospital diagnosis of RA (ICD10 codes M05.X or M06.X) after January 1, 1997, and aged ≥18 years at the date of first diagnosis...

  5. Prostaglandins and Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Mohammad Javad Fattahi

    2012-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic, autoimmune, and complex inflammatory disease leading to bone and cartilage destruction, whose cause remains obscure. Accumulation of genetic susceptibility, environmental factors, and dysregulated immune responses are necessary for mounting this self-reacting disease. Inflamed joints are infiltrated by a heterogeneous population of cellular and soluble mediators of the immune system, such as T cells, B cells, macrophages, cytokines, and prostaglandins (PGs. Prostaglandins are lipid inflammatory mediators derived from the arachidonic acid by multienzymatic reactions. They both sustain homeostatic mechanisms and mediate pathogenic processes, including the inflammatory reaction. They play both beneficial and harmful roles during inflammation, according to their site of action and the etiology of the inflammatory response. With respect to the role of PGs in inflammation, they can be effective mediators in the pathophysiology of RA. Thus the use of agonists or antagonists of PG receptors may be considered as a new therapeutic protocol in RA. In this paper, we try to elucidate the role of PGs in the immunopathology of RA.

  6. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... is Happening to the Joints? Rheumatoid Arthritis: Gaining Control – Working with your Rheumatologist Rheumatoid Arthritis: Additional Conditions ... for Patients Arthritis Drug Information Sheets Benefits and Risks of Opioids in Arthritis Management How to Give ...

  7. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... are available, what is happening in the immune system and what other conditions are associated with RA. ... Rheumatoid Arthritis: Additional Conditions Rheumatoid Arthritis: The Immune System Don’t have SilverLight? Get it here. Updated: ...

  8. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Patient Webcasts / Rheumatoid Arthritis Educational Video Series Rheumatoid Arthritis Educational Video Series This series of five videos ... member of our patient care team. Managing Your Arthritis Managing Your Arthritis Managing Chronic Pain and Depression ...

  9. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Managing Your Arthritis Managing Your Arthritis Managing Chronic Pain and Depression in Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of Life Rehabilitation Management for Rheumatoid Arthritis Patients Rehabilitation of Older Adult ...

  10. Interleukin-6-receptor polymorphisms rs12083537, rs2228145, and rs4329505 as predictors of response to tocilizumab in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Enevold, Christian; Baslund, Bo; Linde, Louise

    2014-01-01

    Tocilizumab (TCZ), a monoclonal antibody targeting the human interleukin-6-receptor (IL-6R), is indicated for the treatment of rheumatoid arthritis (RA). We examined whether three IL6R single-nucleotide polymorphisms rs12083537, rs2228145 (formerly rs8192284), and rs4329505 with previously report...

  11. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Corner / Patient Webcasts / Rheumatoid Arthritis Educational Video Series Rheumatoid Arthritis Educational Video Series This series of five videos ... Your Arthritis Managing Chronic Pain and Depression in Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of Life ...

  12. Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case-control study.

    Science.gov (United States)

    Traylor, Matthew; Curtis, Charles; Patel, Hamel; Breen, Gerome; Hyuck Lee, Sang; Xu, Xiaohui; Newhouse, Stephen; Dobson, Richard; Steer, Sophia; Cope, Andrew P; Markus, Hugh S; Lewis, Cathryn M; Scott, Ian C

    2017-08-01

    To evaluate whether genetic and environmental factors associated with RA in European and Asian ancestry populations are also associated with RA in African ancestry individuals. A case-control study was undertaken in 197 RA cases and 868 controls of African ancestry (Black African, Black Caribbean or Black British ethnicity) from South London. Smoking and alcohol consumption data at RA diagnosis was captured. Genotyping was undertaken (Multi-Ethnic Genotyping Array) and human leukocyte antigen (HLA) alleles imputed. The following European/Asian RA susceptibility factors were tested: 99 genome-wide loci combined into a genetic risk score; HLA region [20 haplotypes; shared epitope (SE)]; smoking; and alcohol consumption. The SE was tested for its association with radiological erosions. Logistic regression models were used, including ancestry-informative principal components, to control for admixture. European/Asian susceptibility loci were associated with RA in African ancestry individuals. The genetic risk score provided an odds ratio (OR) for RA of 1.53 (95% CI: 1.31, 1.79; P = 1.3 × 10 - 7 ). HLA haplotype ORs in European and African ancestry individuals were highly correlated ( r = 0.83, 95% CI: 0.56, 0.94; P = 1.1 × 10 - 4 ). Ever-smoking increased (OR = 2.36, 95% CI: 1.46, 3.82; P = 4.6 × 10 - 4 ) and drinking alcohol reduced (OR = 0.34, 95% CI: 0.20, 0.56; P = 2.7 × 10 - 5 ) RA risk in African ancestry individuals. The SE was associated with erosions (OR = 2.61, 95% CI: 1.36, 5.01; P = 3.9 × 10 - 3 ). Gene-environment RA risk factors identified in European/Asian ancestry populations are relevant in African ancestry individuals. As modern statistical methods facilitate analysing ancestrally diverse populations, future genetic studies should incorporate African ancestry individuals to ensure their implications for precision medicine are universally applicable. © The Author 2017. Published by Oxford University Press on behalf of the British Society for

  13. Sacroiliac joint involvement in classical or definite rheumatoid arthritis

    International Nuclear Information System (INIS)

    Carvalho, A. de; Graudal, H.

    1980-01-01

    In 188 patients with rheumatoid arthritis 564 radiologic examinations of the sacroiliac joints were performed. Severe blurring of the joint space or ankylosis were uncommon. The involvement was related to an age > 40 years at the onset, high values of the ESR and involvement of most joint groups in the limbs and cervical spine. Sex, presence or high titres of the rheumatoid factor and antinuclear antibodies were unrelated to lesions of the sacroiliac joints. A relation to the severity of rheumatoid arthritis rather than to the immunologic condition is suggested. (Auth.)

  14. Liver enlargement demonstrated by scintigraphy in rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Tiger, L.H.; Gordon, M.H.; Ehrlich, G.E.; Shapiro, B.

    1976-03-01

    Scintigraphic scanning employing technetium-99m sulfur colloid was used to assess the size of the liver and spleen in 32 consecutive patients with rheumatoid arthritis. The data were correlated with clinical and laboratory assessment. Seven patients had enlarged livers, three enlarged spleens. An expected correlation of liver enlargement with Sjogren's syndrome did not materialize. Splenic enlargement and liver enlargement were discordant. Liver enlargement correlation best with elevations of rheumatoid factor as measured by latex fixation. As liver enlargement is not an appreciated feature of rheumatoid arthritis, these findings suggest that hepatomegaly need not necessarily imply adverse treatment results or the development of lymphoproliferative disorders.

  15. Incidence and management of infusion reactions to infliximab in 186 italian patient’s with rheumatoid arthritis: the Padua experience

    Directory of Open Access Journals (Sweden)

    S. Todesco

    2011-09-01

    Full Text Available Objective: We report the incidence and treatment of infusion reactions to infliximab, a chimeric monoclonal IgG1 antibody against tumor necrosis factor a, in a large cohort of patients with rheumatoid arthritis. Patients and methods: One hundred eighty six patients with rheumatoid arthritis treated with infliximab for a total of 216.6 patient years were retrospectively evaluated. Patients received 2160 infliximab infusions at the Division of Rheumatology at the University Hospital of Padua from May, 2000 to April, 2004. Specific treatment protocols for initial and subsequent acute infusion reactions were followed and the outcomes documented. Results: The overall incidence of infusion reactions to infliximab was 0.8% (19 out of 2160 of infusions, affecting 10.2% of patients (19 out of 186. Mild, moderate, or severe acute reactions occurred in 0.1% (3 of 2160, 0.6% (13 of 2160, and 0.04% (1 of 2160 of infliximab infusions, respectively. Delayed infusion reactions occurred in 0.09% (2 of 2160 of infusions. Use of specific treatment protocols resulted in rapid resolution of all acute reactions to infliximab. With a prophylaxis protocol, all patients who experienced an initial mild acute reaction were able to receive additional infusions. Conclusions: Using appropriate treatment protocols, infliximab infusion reactions were effectively treated and prevented in patients with mild acute reactions upon retreatment. In the case of moderate to severe infusion reactions, the risks and the benefits of the continuation of infliximab therapy need to be carefully considered.

  16. Monoclonal antibodies to Pneumocystis carinii

    DEFF Research Database (Denmark)

    Kovacs, J A; Halpern, J L; Lundgren, B

    1989-01-01

    To increase understanding of the antigenic structure of Pneumocystis carinii, we developed monoclonal antibodies to rat and human P. carinii. The specificity of the antibodies was demonstrated by immunofluorescence and immunoblot studies. Only one of five monoclonal antibodies to rat P. carinii r...

  17. CHANGES IN THE LEVELS OF ANGIOTENSIN II, ALDOSTERONE, AND FIBROBLAST GROWTH FACTOR IN PATIENTS WITH RHEUMATOID ARTHRITIS IN RELATION TO CLINICAL FEATURES

    Directory of Open Access Journals (Sweden)

    E. B. Komarova

    2016-01-01

    Full Text Available Angiotensin II, aldosterone, and fibroblast growth factor (FGF stimulate neoangiogenesis, fibroblast proliferation, and elaboration of proinflammatory cytokines, which in turn contributes to increased pannus mass and the development of joint tissue destruction in rheumatoid arthritis (RA.Objective: to establish the specific features of changes in the blood levels of angiotensin II, aldosterone, and FGF in patients with RA in relation to the duration and severity of the disease.Subjects and methods. Examinations were made in 194 patients diagnosed with RA without comorbidity; the patients’ mean age was 47.7±10.2 years; the disease duration was 3.82±3.43 years. DAS28 scores for RA were calculated based on C-reactive protein levels. An enzyme immunoassay was used to determine the serum levels of anti-cyclic citrullinated peptide antibodies (ACCPA, angiotensin II, aldosterone, and FGF.Results and discussion. All the examinees were ascertained to have increases in the concentration of angiotensin II and aldosterone in blood by twice and in that of FGF by 2.5 times compared to the controls (p < 0.05. In patients with a RA duration of < 2 years, the blood level of angiotensin II was 25% higher than in those with a RA duration of > 5 years and the concentrations of aldosterone and FGF in patients with long-term RA were twice as high as in those with early RA. In patients with high RA activity, the blood level of angiotensin II was 1.5-fold higher than in those with low and moderate disease activity (p < 0.05. In patients with a high blood ACCPA level, the concentrations of angiotensin II, aldosterone, and FGF were 20, 30, and 25%, respectively, higher than in those with low ACCPA levels. The correlation of DAS28 with blood angiotensin II levels increased with enhanced RA activity. The high aldosterone and FGF values in RA patients are associated with the progression of joint radiographic changes.

  18. Tofacitinib Versus Biologic Treatments in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor Inhibitors: Results From a Network Meta-analysis.

    Science.gov (United States)

    Vieira, Maria-Cecilia; Zwillich, Samuel H; Jansen, Jeroen P; Smiechowski, Brielan; Spurden, Dean; Wallenstein, Gene V

    2016-12-01

    Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This analysis compared the efficacy and safety of tofacitinib with biologic disease-modifying antirheumatic drugs in patients with RA and a prior inadequate response (IR) to tumor necrosis factor inhibitors (TNFi). A systematic literature review identified 5 randomized placebo-controlled trials that evaluated tofacitinib or biologic disease-modifying antirheumatic drugs (bDMARDs) against placebo in patient populations with RA with a prior IR to TNFi. The definition of TNFi-IR varied across studies, and included patients with an IR or who had failed treatment with TNFi for any reason. A network meta-analysis was conducted comparing study data with regard to American College of Rheumatology response rates and Health Assessment Questionnaire-Disability Index improvement at weeks 12 and 24, rates of treatment withdrawal due to all causes; adverse events (AEs) and lack of efficacy; and rates of AEs, serious AEs, and serious infections. The 5 trials included a total of 2136 patients. Tofacitinib 5 mg twice daily combined with methotrexate was found to have relative risk estimates of American College of Rheumatology responses and change from baseline in Health Assessment Questionnaire-Disability Index score comparable with abatacept, golimumab, rituximab, and tocilizumab combined with conventional synthetic disease-modifying antirheumatic drugs. Withdrawal rates from trials due to all causes and AEs were comparable between treatments, and tofacitinib had a lower rate of withdrawals due to lack of efficacy. Rates of AEs and HAQ-DI were comparable between tofacitinib, other active treatments, and placebo. No serious infections were reported with tofacitinib during the placebo-controlled period (up to week 12) in this study population; rates of serious infection with other active treatments were generally low and similar to placebo. During a 24-week period, tofacitinib had efficacy

  19. Thoracic complications of rheumatoid disease

    International Nuclear Information System (INIS)

    Massey, H.; Darby, M.; Edey, A.

    2013-01-01

    Rheumatoid arthritis is a relatively common multisystem disease associated with significant mortality and morbidity. Thoracic disease, both pleural and pulmonary, is a frequent extra-articular manifestation of rheumatoid arthritis and responsible for approximately 20% of rheumatoid-associated mortality. Rheumatoid disease and its associated therapies can affect all compartments of the lung inciting a range of stereotyped pathological responses and it is not infrequent for multiple disease entities to co-exist. In some instances, development of pulmonary complications may precede typical rheumatological presentation of the disease and be the first indication of an underlying connective tissue disease. The spectrum of thoracic disease related to rheumatoid arthritis is reviewed

  20. New monoclonal antibody to human apolipoprotein J

    Czech Academy of Sciences Publication Activity Database

    Čapková, Jana; Geussová, Gizela; Pěknicová, Jana

    2002-01-01

    Roč. 2002, č. 48 (2002), s. 40-42 ISSN 0015-5500 R&D Projects: GA ČR GV524/96/K162 Grant - others:NFDK-MAOB(XE) 1985-NFDK-MAOB Institutional research plan: CEZ:AV0Z5052915 Keywords : apo J * human spermatoza * monoclonal antibody Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.615, year: 2002

  1. Tocilizumab in the treatment of rheumatoid arthritis and beyond

    Directory of Open Access Journals (Sweden)

    Shetty A

    2014-03-01

    Full Text Available Anjali Shetty,1 Rebekah Hanson,1 Peter Korsten,2 Munir Shawagfeh,3 Shiva Arami,1 Suncica Volkov,1 Olga Vila1 William Swedler,1 Abdel Naser Shunaigat,4 Sameer Smadi,4 Ray Sawaqed,5 David Perkins,1 Shiva Shahrara,1 Nadera J Sweiss11Department of Rheumatology, Pharmacy, Transplant, University of Illinois at Chicago, Chicago, IL, USA; 2Department of Nephrology and Rheumatology, University Medicine Göttingen, Göttingen, Germany; 3Anesthesia and Pain Management, King Hussein Cancer Center, Amman, Jordan; 4Liver Transplant, Kidney Transplant Royal Medical Services, Jordan; 5Cardiac Surgery Methodist Hospitals, Merrillville, IN, USAAbstract: Rheumatoid arthritis (RA is a systemic inflammatory disease characterized by joint pain, swelling, stiffness, and progressive destruction of the small joints of the hands and feet. Treatment of RA has improved over the past decade. With multiple cytokines well-known now to play a role in the pathogenesis of RA, including tumor necrosis factor alpha, interleukin (IL-1β, and IL-6, many targeted biological treatments against these cytokines have emerged, changing the treatment of this disease. Tocilizumab (TCZ is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs (DMARDs or cannot tolerate other approved drug classes for RA. The aim of this review is to discuss the role of IL-6 in RA, and to provide an overview of the mode of action, pharmacokinetics, and safety of TCZ. Furthermore, efficacy studies of TCZ as both monotherapy and combination therapy will be evaluated. There have been several important clinical trials evaluating the efficacy and safety of TCZ in RA patients; this review summarizes this data from 14 key trials with emphasis on Phase III trials. Review of these trials

  2. Paradoxical Reaction to Golimumab: Tumor Necrosis Factor α Inhibitor Inducing Psoriasis Pustulosa

    Directory of Open Access Journals (Sweden)

    Marien Siqueira Soto Lopes

    2013-11-01

    Full Text Available Importance: Golimumab is a human monoclonal antibody, used for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Adverse reactions are increasing with this class of medication (tumor necrosis factor α inhibitors. Observations: The authors present a case of a female patient who presented with psoriasis pustulosa after the use of golimumab for rheumatoid arthritis. Conclusions and Relevance: Paradoxically, in this case, golimumab, which is used for psoriasis, induced the pustular form of this disease. We are observing an increasing number of patients who develop collateral effects with tumor necrosis factor α inhibitors, and the understanding of the mechanism of action and how these adverse reactions occur may contribute to avoid these sometimes severe situations.

  3. [Management of rheumatoid arthritis].

    Science.gov (United States)

    Fiehn, C; Krüger, K

    2016-11-01

    Rheumatoid arthritis is the most common inflammatory rheumatic disease. Due to the destruction of joints in the course of the disease it leads to significant morbidity in affected patients. The quality of life and even life expectancy can be severely impaired. Early diagnosis and early initiation of treatment is a decisive step towards a more benign course of the disease. New classification criteria have been published in order to help in early diagnosis. Methods of imaging, such as ultrasound and magnetic resonance imaging help in the detection of synovitis, which is the major pathomorphological manifestation of arthritis and should be identified without any doubt. Treatment follows the rule of treat to target with the aim of achieving remission or if this is not realistic, at least the lowest possible level of disease activity. The first and perhaps most important step in therapy is the initiation of methotrexate or if contraindications are present, another disease-modifying antirheumatic drug (DMARD) as soon as the diagnosis is made. Initial addition of glucocorticoids is recommended, which should be reduced in dose and terminated as soon as possible. Furthermore, either the combination of different DMARDs or the start of biologic DMARDs, such as tumor necrosis factor alpha (TNF-alpha) inhibitors or second generation biologic DMARDs is possible as a treatment option. The treatment follows the rule of shared decision-making and is the standard to treat comorbidities, the use an interdisciplinary approach and to treat functional deficits by rehabilitation measures, such as physiotherapy.

  4. Factor structure of the arthritis body experience scale (ABES) in a U.S. population of people with osteoarthritis (OA), rheumatoid arthritis (RA), fibromyalgia (FM) and other rheumatic conditions.

    Science.gov (United States)

    Boyington, J E A; Devellis, R; Shreffler, J; Schoster, B; Callahan, L F

    2008-01-01

    To examine the psychometric properties of the Arthritis Body Experience Scale (ABES) in a US sample of people with osteoarthritis, rheumatoid arthritis, fibromyalgia and other rheumatic conditions. The ABES, with the scoring direction modified, was phone-administered to 937 individuals who self-identified as having one or more arthritis conditions based on a validated, US, national survey assessment tool. Descriptive statistics of demographic variables and factor analysis of scale items were conducted. Scale dimensionality was assessed using principal component analysis (PCA) with oblique rotation. Criteria for assessing factors were eigenvalues > 1, visual assessment of scree plot, and structure and pattern matrices. The predominantly female (74.2%) and Caucasian (79.9%) sample had a mean age of 61.0 ± 13.1 years, and a mean BMI of 30.2 ± 7.1. Major arthritis conditions reported were rheumatoid arthritis, osteoarthritis and fibromyalgia. A three-factor structure with cronbach alpha values of .84, .85 and .53 was elicited, and accounted for 72% of the variance. Compared to the two-factor structure evidenced by the original ABES scale in a sample of UK adults, the data from this sample evidenced a three-factor structure with higher variance. The third factor's cronbach alpha of .53 was low and could be improved by the addition of salient questions derived from further qualitative interviews with patients with arthritis and other rheumatic conditions and from current literature findings. The observed psychometrics indicate the scale usefully assesses body image in populations with arthritis and related conditions. However, further testing and refinement is needed to determine its utility in clinical and other settings.

  5. Study on serum TNF-α level, B-cell count and T-cell subsets distribution in peripheral blood in patients with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Shi Buqing

    2006-01-01

    Objective: To study the changes of serum TNF-α levels, B-cell count and T-cell subsets distribution in peripheral blood in patients with rheumatoid arthritis. Methods: Serum TNF-α levels (with RIA), B cell as well as T cell subsets distribution type (with monoclonal antibody technique) were examined in 37 patients with rheumatoid arthritis and 30 controls. Results Serum TNF-α levels and B lymphocytes count were significantly higher in the patients than those in controls (P 3 , CD 4 and CD 4 /CD 8 were obviously lower (P<0.01). Conclusion: Rheumatoid arthritis is an autoimmune disease with abnormal immunoregulation. (authors)

  6. Biodistribution mechanisms of therapeutic monoclonal antibodies in health and disease.

    Science.gov (United States)

    Tabrizi, Mohammad; Bornstein, Gadi Gazit; Suria, Hamza

    2010-03-01

    The monoclonal antibody market continues to witness an impressive rate of growth and has become the leading source of expansion in the biologic segment within the pharmaceutical industry. Currently marketed monoclonal antibodies target a diverse array of antigens. These antigens are distributed in a variety of tissues such as tumors, lungs, synovial fluid, psoriatic plaques, and lymph nodes. As the concentration of drug at the proximity of the biological receptor determines the magnitude of the observed pharmacological responses, a significant consideration in effective therapeutic application of monoclonal antibodies is a thorough understanding of the processes that regulate antibody biodistribution. Monoclonal antibody distribution is affected by factors such as molecular weight, blood flow, tissue and tumor heterogeneity, structure and porosity, target antigen density, turnover rate, and the target antigen expression profile.

  7. Disease modifying and antiangiogenic activity of 2-Methoxyestradiol in a murine model of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Moore Elizabeth G

    2009-05-01

    Full Text Available Abstract Background A critical component of disease progression in rheumatoid arthritis (RA involves neovascularization associated with pannus formation. 2-methoxyestradiol (2ME2 is a naturally occurring molecule with no known physiologic function, although at pharmacologic concentrations it has antiproliferative and antiangiogenic activities. We investigated the impact of orally administered 2ME2 on the initiation and development of proliferative synovitis using the anti-collagen monoclonal antibodies (CAIA model. Methods Severe polyarticular arthritis was induced in Balb/c female mice by administration of 2 mg of a monoclonal antibody cocktail intravenously into the tail vein of mice. Twenty-four hours following monoclonal antibody administration, mice were injected with 25 μg of LPS (E. coli strain 0111:B4 via the intraperitoneal route. Treatment with 2ME2 (100, 75, 50, 25, 10, 1 mg/kg, p.o., daily, or vehicle control began 24 hrs following LPS challenge and continued to day 21. Hind limbs were harvested, sectioned and evaluated for DMARD activity and general histopathology by histomorphometric analysis and immunohistochemistry (vWF staining. In a separate study, different dosing regimens of 2ME2 (100 mg/kg; q.d. vs q.w. vs q.w. × 2 were evaluated. The effect of treatment with 2ME2 on gene expression of inflammatory cytokines and angiogenic growth factors in the joint space was evaluated 5 and 14 days after the induction of arthritis. Results Mice treated with 2ME2 beginning 24 hours post anti-collagen monoclonal antibody injection, showed a dose-dependent inhibition in mean arthritic scores. At study termination (day 21, blinded histomorphometric assessments of sectioned hind limbs demonstrated decreases in synovial inflammation, articular cartilage degradation, pannus formation, osteoclast activity and bone resorption. At the maximal efficacious dosing regimen (100 mg/kg/day, administration of 2ME2 resulted in total inhibition of the

  8. Outcome after 40 years with rheumatoid arthritis : a prospective study of function, disease activity and mortality

    NARCIS (Netherlands)

    Minaur, Nicola J.; Jacoby, Richard K.; Cosh, John A.; Taylor, Gordon; Rasker, Johannes J.

    2004-01-01

    In an inception cohort of 100 patients with rheumatoid arthritis (RA) we studied course and outcome after 40 years, regarding function, disease activity, cause and age of death, and prognostic factors. Function, joint count, erythrocyte sedimentation rate (ESR), hemoglobin (Hb), rheumatoid factor

  9. Rheumatoid Arthritis: "You Are Not Alone."

    Science.gov (United States)

    ... page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Rheumatoid Arthritis: "You Are Not Alone." Past Issues / Summer 2014 ... Alternative Medicine http://nccam.nih.gov NIHSeniorHealth.gov—Rheumatoid Arthritis ... ...

  10. Rheumatoid Arthritis: Can It Affect the Eyes?

    Science.gov (United States)

    Rheumatoid arthritis: Can it affect the eyes? Can rheumatoid arthritis affect the eyes? Answers from April Chang-Miller, M.D. Rheumatoid arthritis is a chronic inflammatory disease that primarily affects the ...

  11. Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis.

    OpenAIRE

    Gerards, A.H.; Lathouder, de, S; Groot, E.R.; Dijkmans, B.A.C.; Aarden, L.A.

    2003-01-01

    OBJECTIVES: To analyse whether the beneficial effects of methotrexate in rheumatoid arthritis (RA) could be due to inhibition of inflammatory cytokine production. METHODS: Cytokine production was studied using whole blood (WB) and mononuclear cells (MNC) of healthy volunteers and RA patients. Cultures were stimulated with either bacterial products such as lipo-oligosaccharide (LOS) or Staphylococcus aureus Cowan I (SAC) to activate monocytes or with monoclonal antibodies to CD3 and CD28 to in...

  12. Targeting interleukin-15 in patients with rheumatoid arthritis: a proof-of-concept study

    DEFF Research Database (Denmark)

    Baslund, Bo; Tvede, Niels; Danneskiold-Samsøe, Bente

    2005-01-01

    Interleukin-15 (IL-15) is a proinflammatory, innate response cytokine that mediates pleiotropic effector function in rheumatoid arthritis (RA) inflammatory synovitis. Our objective was to study the ability of HuMax-IL15, a human IgG1 anti-IL-15 monoclonal antibody, to neutralize exogenous...... and endogenous IL-15 activity in vitro and to perform a phase I-II dose-escalation trial with HuMax-IL15 in patients with active RA....

  13. Nuclear Factor κB is required for tumor growth inhibition mediated by enavatuzumab (PDL192, a humanized monoclonal antibody to TweakR

    Directory of Open Access Journals (Sweden)

    James W. Purcell

    2014-01-01

    Full Text Available TweakR is a TNF receptor family member, whose natural ligand is the multifunctional cytokine TWEAK. The growth inhibitory activity observed following TweakR stimulation in certain cancer cell lines and the overexpression of TweakR in many solid tumor types led to the development of enavatuzumab (PDL192, a humanized IgG1 monoclonal antibody to TweakR. The purpose of this study was to determine the mechanism of action of enavatuzumab’s tumor growth inhibition and to provide insight into the biology behind TweakR as a cancer therapeutic target. A panel of 105 cancer lines was treated with enavatuzumab in vitro; and 29 cell lines of varying solid tumor backgrounds had >25% growth inhibition in response to the antibody. Treatment of sensitive cell lines with enavatuzumab resulted in the in vitro and in vivo (xenograft activation of both classical (p50, p65 and non-classical (p52, RelB NFκB pathways. Using NFκB DNA binding functional ELISAs and microarray analysis, we observed increased activation of NFκB subunits and NFκB regulated genes in sensitive cells over that observed in resistant cell lines. Inhibiting NFκB subunits (p50, p65, RelB, p52 and upstream kinases (IKK1, IKK2 with siRNA and chemical inhibitors consistently blocked enavatuzumab’s activity. Furthermore, enavatuzumab treatment resulted in NFκB-dependent reduction in cell-division as seen by the activation of the cell cycle inhibitor p21 both in vitro and in vivo. The finding that NFκB drives the growth inhibitory activity of enavatuzumab suggests that targeting TweakR with enavatuzumab may represent a novel cancer treatment strategy.

  14. Dissecting Immunogenicity of Monoclonal Antibodies

    National Research Council Canada - National Science Library

    Snyder, Christopher

    2003-01-01

    The potential of monoclonal antibodies, (mAbs), for use in therapeutic and diagnostic applications has not been fully realized in part due to counter-immune responses that often arise in patient recipients of mAb...

  15. Including adverse drug events in economic evaluations of anti-tumour necrosis factor-α drugs for adult rheumatoid arthritis: a systematic review of economic decision analytic models.

    Science.gov (United States)

    Heather, Eleanor M; Payne, Katherine; Harrison, Mark; Symmons, Deborah P M

    2014-02-01

    Anti-tumour necrosis factor-α drugs (anti-TNFs) have revolutionised the treatment of rheumatoid arthritis (RA). More effective than standard non-biological disease-modifying anti-rheumatic drugs (nbDMARDs), anti-TNFs are also substantially more expensive. Consequently, a number of model-based economic evaluations have been conducted to establish the relative cost-effectiveness of anti-TNFs. However, anti-TNFs are associated with an increased risk of adverse drug events (ADEs) such as serious infections relative to nbDMARDs. Such ADEs will likely impact on both the costs and consequences of anti-TNFs, for example, through hospitalisations and forced withdrawal from treatment. The aim of this review was to identify and critically appraise if, and how, ADEs have been incorporated into model-based cost-effectiveness analyses of anti-TNFs for adult patients with RA. A systematic literature review was performed. Electronic databases (Ovid MEDLINE; Ovid EMBASE; Web of Science; NHS Economic Evaluations Database) were searched for literature published between January 1990 and October 2013 using electronic search strategies. The reference lists of retrieved studies were also hand searched. In addition, the National Institute for Health and Care Excellence technology appraisals were searched to identify economic models used to inform UK healthcare decision making. Only full economic evaluations that had used an economic model to evaluate biological DMARDs (bDMARDs) (including anti-TNFs) for adult patients with RA and had incorporated the direct costs and/or consequences of ADEs were critically appraised. To be included, studies also had to be available as a full text in English. Data extracted included general study characteristics and information concerning the methods used to incorporate ADEs and any associated assumptions made. The extracted data were synthesised using a tabular and narrative format. A total of 43 model-based economic evaluations of bDMARDs for adult RA

  16. Rheumatoid arthritis: Radiological changes in the cervical spine

    International Nuclear Information System (INIS)

    Al-Boukai, Ahmad A.; Al-Arfaj, Abdurahman S.

    2003-01-01

    Objective was to describe the radiographic cervical spine changes in rheumatoid arthritis patients.Forty-nine patients (37 females and 12 males ) diagnosed with rheumatoid arthritis at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between June 1998 and December 2000, were studied for their radiographic cervical spine changes . Their mean age at disease onset was 41.4 + 13.4 years (range of 18-73)and mean duration of disease was 9.1+-6.28 years (range of 2-34). Their demographic data including rheumatoid factor status was obtained. Standard conventional radiographs cervical spine were obtained to study the cervical spine changes. Cervical radiographic changes were found in 34 patients (27 females and 7 males) 10 had subluxation (7 with atlanto-axial subluxation,2 with sub-axial subluxation,and one with lateral subluxation ). No vertical impaction was seen. Erosion of odontoid process was seen in one patient .All were rheumatoid seropositive Cervical spine changes in patients with rheumatoid arthritis are common, in particular subluxation in the upper cervical spine. Our study showed somewhat lesser prevalence of these changes. These were clinically correlated with disease duration, female sex, and rheumatoid factor, but were not clinically significant. (author)

  17. Tocilizumab: A Review of Its Safety and Efficacy in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Graeme Jones

    2010-01-01

    Full Text Available Recent years have seen many exciting developments in the treatment of rheumatoid arthritis. Tocilizumab (TCZ is a monoclonal antibody which inhibits the interleukin-6 receptor. After initial studies in Japan, it has been extensively studied in five multicentre clinical trials. This report summarises the key efficacy and toxicity findings from the major clinical trials. TCZ works quickly and effectively in rheumatoid arthritis either as monotherapy or in combination with other agents in early disease, DMARD inadequate responders, seronegative disease and after anti-TNF failure. The toxicity profile is manageable but includes infections (most notably skin and soft tissue, increases in serum cholesterol, transient decreases in neutrophil count and abnormal liver function tests (especially in combination with methotrexate. In summary, there is sufficient evidence to make TCZ a first line biologic therapy for rheumatoid arthritis especially for those who are unable to take methotrexate or who fail anti-TNF therapy.

  18. Biologic interventions for fatigue in rheumatoid arthritis.

    Science.gov (United States)

    Almeida, Celia; Choy, Ernest H S; Hewlett, Sarah; Kirwan, John R; Cramp, Fiona; Chalder, Trudie; Pollock, Jon; Christensen, Robin

    2016-06-06

    Fatigue is a common and potentially distressing symptom for patients with rheumatoid arthritis (RA), with no accepted evidence-based management guidelines. Evidence suggests that biologic interventions improve symptoms and signs in RA as well as reducing joint damage. To evaluate the effect of biologic interventions on fatigue in rheumatoid arthritis. We searched the following electronic databases up to 1 April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Controlled Trials Register, the National Research Register Archive, The UKCRN Portfolio Database, AMED, CINAHL, PsycINFO, Social Science Citation Index, Web of Science, and Dissertation Abstracts International. In addition, we checked the reference lists of articles identified for inclusion for additional studies and contacted key authors. We included randomised controlled trials if they evaluated a biologic intervention in people with rheumatoid arthritis and had self reported fatigue as an outcome measure. Two reviewers selected relevant trials, assessed methodological quality and extracted data. Where appropriate, we pooled data in meta-analyses using a random-effects model. We identified 32 studies for inclusion in this current review. Twenty studies evaluated five anti-tumour necrosis factor (anti-TNF) biologic agents (adalimumab, certolizumab, etanercept, golimumab and infliximab), and 12 studies focused on five non-anti-TNF biologic agents (abatacept, canakinumab, rituximab, tocilizumab and an anti-interferon gamma monoclonal antibody). All but two of the studies were double-blind randomised placebo-controlled trials. In some trials, patients could receive concomitant disease-modifying anti-rheumatic drugs (DMARDs). These studies added either biologics or placebo to DMARDs. Investigators did not change the dose of the latter from baseline. In total, these studies included 9946 participants in the intervention groups and

  19. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Arthritis and Health-related Quality of Life Rehabilitation Management for Rheumatoid Arthritis Patients Rehabilitation of Older Adult Patients with Arthritis Complementary ...

  20. Preclinical pharmacokinetics, interspecies scaling, and pharmacokinetics of a Phase I clinical trial of TTAC-0001, a fully human monoclonal antibody against vascular endothelial growth factor 2

    Directory of Open Access Journals (Sweden)

    Lee WS

    2018-03-01

    Full Text Available Weon Sup Lee,1 Sang Ryeol Shim,1 Seon Young Lee,1 Jin San Yoo,1 Sung Kweon Cho2 1PharmAbcine, Inc., Daejeon, Republic of Korea; 2Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea Background: VEGF is a highly selective mitogen that serves as the central regulator of tumor angiogenesis by mediating endothelial proliferation, permeability, and survival. Tanibirumab (TTAC-0001 is a fully human IgG1 monoclonal antibody derived from a fully human naïve single-chain variable fragment (ScFv phage library that was developed to inhibit the effects of VEGF in the treatment of solid tumors, especially those of the brain. Methods: In the present study, we conducted intravenous pharmacokinetic studies of TTAC-0001 in mice, rats, and cynomolgus monkeys. At the doses studied (3 mg/kg, 10 mg/kg, 30 mg/kg, TTAC-0001 exhibited dose proportionality in mice and monkeys. At a dose of ~10 mg/kg, the clearance of TTAC-0001 from serum was 0.017 mL/h in mice, 0.35 mL/h in rats, and 2.19 mL/h in cynomolgus monkeys, and the terminal half-life ranged from 20–30 h among the three species. Pharmacokinetic data in mice, rats, and cynomolgus monkeys were used to predict the pharmacokinetics of TTAC-0001 in humans using allometric scaling. The predicted serum clearance of TTAC-0001 in humans was 102.45 mL/h and the terminal half-life was 27.52 h. Results: The maximum life span-corrected clearance value was 72.92 mL/h. The observed clearance in humans was more similar to the predicted scaled clearance. Conclusion: We investigated the pharmacokinetics of TTAC-0001 in mice, rats, and cynomolgus monkeys after intravenous administration. At the doses studied, TTAC-0001 exhibited dose proportionality in mice and monkeys. The scaled pharmacokinetics of TTAC-0001 reported here was useful for designing first-in-human studies. Allometric scaling in the therapeutic antibody is feasible. Keywords: VEGF2, tanibirumab, pharmacokinetics

  1. Neutron capture therapy of epidermal growth factor receptor (EGFR)vIII positive gliomas using boronated monoclonal antibody L8A4

    International Nuclear Information System (INIS)

    Yang, Weilian; Barth, Rolf F.; Wu, Gong

    2006-01-01

    The purpose of the present study was to evaluate the EGFRvIII specific monoclonal antibody, L8A4 as a boron delivery agent for NCT of the receptor (+) rat glioma, F98 npEGFRvIII . A heavily boronated polyamidoamine (PAMAM) dendrimer (BD) was linked to L8A4 by means of heterobifunctional reagents. Wild type (F98 WT ) receptor(-) or EGFRvIII human gene transfected receptor(+) F98 npEGFRvIII glioma cells were implanted into the brains of Fischer rats. Biodistribution studies were initiated 14 d later. Animals received 125 I-labeled BD-L8A4 by either convection enhanced delivery (CED) or intratumoral(i.t.) injection and were euthanized 6, 12, 24 or 48 h later. At 6 h following CED, equivalent amounts of the bioconjugate were detected in receptor(+) and (-) tumors, but by 24 h the amounts retained by receptor(+) gliomas were 60.1% following CED and 43.7% following i.t. injection, compared to 14.6% ID/g by receptor(-) tumors. Tumor boron concentrations were 32.7 and 44.5 μg/g, respectively, for BD-L8A4 alone or in combination with i.v. BPA. BNCT was carried out at the MITR-II Reactor 24 h after CED of BD-L8A4 (∼40 μg 10 B/∼750 μg protein) and 2.5 h after i.v. injection of BPA (500 mg/kg). Rats that received BD-L8A4 alone or in combination with BPA had mean survival times of 70.4 and 85d, respectively, with 20% and 10% long term survivors, respectively, compared to 40.1 d for i.v. BPA and 30.3 and 26.3 d for irradiated and untreated controls, respectively. These data convincingly demonstrate the therapeutic efficacy of molecular targeting of EGFRvIII and should provide a platform for the future development of combinations of high and low molecular weight delivery agents for BNCT of brain tumors. (author)

  2. [New therapies for rheumatoid arthritis].

    Science.gov (United States)

    Salgado, Eva; Maneiro, José Ramón

    2014-11-18

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammation of the synovial membrane and progressive destruction of the articular cartilage and bone. Advances in the knowledge of disease pathogenesis allowed the identification of novel therapeutic targets such as tumor necrosis factor (TNF), interleukin (IL)-1, IL-6 or the system JAK/STAT phosphorylation. At present there are 5 TNF antagonists approved for RA. Tocilizumab blocks the pathway of IL-6 and is the only biological with proven efficacy in monotherapy. Rituximab modulates B cell response in RA. Abatacept provided new data on T cell involvement in the pathogenesis of RA. Tofacitinib is the first kinase inhibitor approved for this disease. Biologic drugs have proven efficacy, almost always in combination with methotrexate, and even halt radiographic progression. Monitoring infection is the main precaution in handling these patients. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  3. Profile of sarilumab and its potential in the treatment of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Raimondo MG

    2017-05-01

    Full Text Available Maria Gabriella Raimondo,1 Martina Biggioggero,1 Chiara Crotti,1 Andrea Becciolini,2 Ennio Giulio Favalli2 1Department of Clinical Sciences and Health Community, Division of Rheumatology, University of Milan, 2Department of Rheumatology, Gaetano Pini Institute, Milan, Italy Abstract: In recent years the use of biotechnological agents has drastically revolutionized the therapeutic approach and the progression of rheumatoid arthritis (RA. In particular, interleukin-6 (IL-6 has been demonstrated as a pivotal cytokine in the pathogenesis of the disease by contributing to both the innate and the adaptive immune system perturbation, and to the production of acute-phase proteins involved in the systemic expression of the disorder. The first marketed IL-6 blocker was tocilizumab, a humanized anti-IL-6 receptor (anti-IL-6R monoclonal antibody. The successful use of tocilizumab in RA has encouraged the development of other biologic agents specifically targeting the IL-6 pathway, either directed against IL-6 cytokine (sirukumab, olokizumab, and clazakizumab or IL-6 receptor (sarilumab. One Phase II and six Phase III randomized controlled trials demonstrated a broad efficacy of sarilumab across all RA patient subtypes, ranging from methotrexate (MTX to tumor necrosis factor inhibitor insufficient responders. In particular, sarilumab as monotherapy demonstrated a clear head-to-head superiority over adalimumab in MTX-intolerant subjects. In addition, compared with tocilizumab, sarilumab showed a similar safety profile with significantly higher affinity and longer half-life, responsible for a reduction of the frequency of administration (every other week instead weekly. All these aspects may be important in defining the strategy for positioning sarilumab in the treatment algorithm of RA. Indeed, observational data coming from post-marketing real-life studies may provide crucial additional information for better understanding the role of sarilumab in the

  4. Tracheobronchomegaly and rheumatoid arthritis

    International Nuclear Information System (INIS)

    Rua Marin, Catalina; Diaz Betancur, James Samir; Cardona, Alejandro; Ramirez Gomez, Luis Alberto

    2008-01-01

    Tracheobronchomegaly is a rare condition of unknown etiology that has been described in association with connective tissue diseases. We present a case of tracheomegaly in a patient with a long evolution rheumatoid arthritis. This is the second case reported in the medical literature until now. Association between these pathologies is uncertain and we can not establish a clear pathophysiological link due to the rarity of its occurrence and the late onset of symptoms

  5. Obtenção e caracterização de anticorpo monoclonal murino anti-fator VIII da coagulação sangüínea Attainment and characterization of murine monoclonal anti-factor VIII antibodies

    Directory of Open Access Journals (Sweden)

    Rosana Rossi-Ferreira

    2006-06-01

    Full Text Available Entre os avanços da engenharia celular e biotecnologia nas últimas décadas, destaca-se a produção de anticorpos monoclonais murinos (AcMm utilizados no aprimoramento diagnóstico nas rotinas laboratoriais. A produção de fator VIII de alta pureza sempre foi o desejo e a preocupação das indústrias de hemoderivados para tratamento de pacientes portadores de hemofilia A, porém este produto inexiste no Brasil, sendo necessária sua obtenção no mercado internacional a custos elevados. O trabalho tem por objetivo a produção de AcMm anti-fator VIII humano (FVIII H através da expansão dos clones e caracterização imunoquímica do anticorpo. Camundongos Balb/c foram imunizados com FVIII H purificado como também proveniente de crioprecipitado e as células esplênicas dos animais foram fusionadas com células mielomatosas murinas segundo o método descrito por Kohler e Milstein para produção de híbridos em cultura. Foram testados 1.983 híbridos dos quais 105 foram submetidos à clonagem. Destes, 39 obtiveram monoclonalidade e 7 destes clones foram caracterizados através de técnicas de immunoblotting. Foram submetidas à purificação por cromatografia três imunoglobulinas de diferentes classes pertencentes aos clones LAMB1-10A1A4, LAMB1-17A1A1 e LAMB1-24A2A1. A imunoglobulina purificada pertencente ao clone LAMB1-10A1A4 foi adsorvida em coluna de imunoafinidade para purificação de concentrado de FVIII proveniente de crioprecipitado plasmático.Among the advances in cellular engineering and biotechnology over the last decades, the production of murine monoclonal antibodies (AcMm, used to improve laboratory diagnoses, stands out. The production of very pure factor VIII has always been a concern of suppliers of blood products to treat patients with hemophilia A and this product is still not produced in Brazil. Hence, it can only be attained on the international market at a high cost. The aim of this work was to produce AcMm anti-factor

  6. The marked and rapid therapeutic effect of tofacitinib in combination with subcutaneous methotrexate in a rheumatoid arthritis patient with poor prognostic factors who is resistant to standard disease-modifying antirheumatic drugs and biologicals: A clinical case

    Directory of Open Access Journals (Sweden)

    N. V. Demidova

    2016-01-01

    Full Text Available Today, it is generally accepted that it is necessary to achieve clinical remission in rheumatoid arthritis (RA or as minimum a low disease activity. The paper describes a clinical case of a female patient diagnosed with RA who was observed to have inefficiency of standard disease-modifying antirheumatic therapy with methotrexate 25 mg/week, secondary inefficiency of tumor necrosis factor-α inhibitors (adalimumab, and inefficiency/poor tolerance of the interlukin-6 receptor antagonist tocilizumab. This determined the need to use fofacitinib (TOFA, a drug with another mechanism of action. TOFA is the first agent from a new group of immunomodulatory and anti-inflammatory drugs, intracellular kinase inhibitors. Disease remission could be achieved during therapy with TOFA, which enables one to consider this synthetic drug as a therapy option that potentially competes with therapy with biologicals.

  7. Leflunomide in the treatment of rheumatoid arthritis. An analysis of predictors for treatment continuation

    NARCIS (Netherlands)

    van Roon, EN; Hoekstra, M; Tobi, H; Jansen, TLTA; Bernelot Moens, HJ; Brouwers, JRBJ; van de Laar, MAFJ

    Aims To determine factors predictive for leflunomide drug survival in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. Methods A standard dataset was collected from medical records of consecutive outpatients on leflunomide treatment for rheumatoid arthritis between

  8. What employees with rheumatoid arthritis, diabetes mellitus and hearing loss need to cope at work

    NARCIS (Netherlands)

    Detaille, Sarah I.; Haafkens, Joke A.; van Dijk, Frank J. H.

    2003-01-01

    Objectives This study attempted to determine factors that help currently employed people with rheumatoid arthritis, diabetes mellitus or hearing loss to continue working. Methods This was a qualitative study that used three concept-mapping sessions. Sixty-nine participants (rheumatoid arthritis 21,

  9. Coexisting ankylosing spondylitis and rheumatoid arthritis: a case report with literature review.

    Science.gov (United States)

    Guo, Ying-Ying; Yang, Li-Li; Cui, Hua-Dong; Zhao, Shuai; Zhang, Ning

    2011-10-01

    A 30-year-old female patient with coexisting ankylosing spondylitis and rheumatoid arthritis was diagnosed and treated. The human leukocyte antigen (HLA)-B27 is a predisposing factor of ankylosing spondylitis and HLA-DR4 is a predisposing factor of rheumatoid arthritis. This patient was HLA-B27 and HLA-DR4 positive, and ankylosing spondylitis manifested before rheumatoid arthritis. After disease modifying anti-rheumatic drugs successfully arrested ankylosing spondylitis activity the patient conceived and delivered a healthy baby. One year later, she developed peripheral polyarthritis and was diagnosed with rheumatoid arthritis. We hypothesized that pregnancy may be one of the environmental factors that can activate rheumatoid arthritis, and that disease modifying anti-rheumatic drugs play an important role in keeping the disease under control.

  10. Rheumatoid Arthritis Educational Video Series

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    Full Text Available ... treatments are available, what is happening in the immune system and what other conditions are associated with RA. ... Rheumatologist Rheumatoid Arthritis: Additional Conditions Rheumatoid Arthritis: The Immune System Don’t have SilverLight? Get it here. Updated: ...

  11. The impact of using musculoskeletal ultrasound imaging and other influencing factors on medication adherence in patients with rheumatoid arthritis: a qualitative study

    Directory of Open Access Journals (Sweden)

    Kumar K

    2016-06-01

    Full Text Available Kanta Kumar,1,2 Karim Raza,3,4 Paramjit Gill,1 Sheila Greenfield1 1Primary Care Clinical Sciences, University of Birmingham, Birmingham, 2Faculty of Medical and Human Sciences, University of Manchester, Manchester, 3Institute of Inflammation and Ageing, University of Birmingham, 4Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK Background: Medication can ease symptoms and limit disease progression in rheumatoid arthritis (RA. Despite this, nonadherence to medication is common in RA. We explored the determinants of high and low adherence to disease-modifying antirheumatic drugs (DMARDs in patients with RA and provide suggestions on approaches to improving adherence to DMARDs.Methods: Patients with RA were identified from those who had previously participated in a questionnaire measuring levels of medication adherence. Twenty patients participated (ten high and ten low adherers, as determined by responses to the Medication Adherence Report Scale. In-depth individual semistructured interviews were undertaken until data saturation was reached. Interviews were transcribed and analyzed using a constant comparative method.Results: Four main themes related to adherence were identified: 1 symptom severity; 2 illness perception; 3 perceived benefits and risks of DMARDs; and 4 the quality and quantity of information about RA and DMARDs. In addition, patients’ suggestions about strategies to optimize adherence to DMARDs were captured and they fell within the following themes: 1 musculoskeletal ultrasound to explain the disease process and to provide objective feedback about the extent to which their disease activity is being effectively controlled; 2 better explanations of the consequences of poorly controlled RA; and 3 a good relationship with the health professional.Conclusion: Patients’ beliefs about medicines, perceptions about RA, and level of satisfaction with information about DMARDs influenced their adherence to DMARDs. The use

  12. Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis

    Science.gov (United States)

    Burska, Agata N.; Hunt, Laura; Strollo, Rocky; Ryan, Brent J.; Vital, Ed; Nissim, Ahuva; Winyard, Paul G.; Emery, Paul; Ponchel, Frederique

    2014-01-01

    Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described. Such PTM introduce neoepitopes in proteins that can generate novel autoantibody specificities. The recent recognition of these novel specificities in RA provides a unique opportunity to understand human B-cell development in vivo. In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation. With the advancement of research methodologies it should be expected that other autoantibodies against PTM proteins could be discovered in patients with autoimmune diseases. Many of such autoantibodies may provide significant biomarker potential. PMID:24782594

  13. High titers of both rheumatoid factor and anti-CCP antibodies at baseline in patients with rheumatoid arthritis are associated with increased circulating baseline TNF level, low drug levels, and reduced clinical responses: a post hoc analysis of the RISING study.

    Science.gov (United States)

    Takeuchi, Tsutomu; Miyasaka, Nobuyuki; Inui, Takashi; Yano, Toshiro; Yoshinari, Toru; Abe, Tohru; Koike, Takao

    2017-09-02

    Although both rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) are useful for diagnosing rheumatoid arthritis (RA), the impact of these autoantibodies on the efficacy of tumor necrosis factor (TNF) inhibitors has been controversial. The aim of this post hoc analysis of a randomized double-blind study (the RISING study) was to investigate the influences of RF and anti-CCP on the clinical response to infliximab in patients with RA. Methotrexate-refractory patients with RA received 3 mg/kg of infliximab from weeks 0 to 6 and then 3, 6, or 10 mg/kg every 8 weeks from weeks 14 to 46. In this post hoc analysis, patients were stratified into three classes on the basis of baseline RF/anti-CCP titers: "low/low-C" (RF < 55 IU/ml, anti-CCP < 42 U/ml), "high/high-C" (RF ≥ 160 IU/ml, anti-CCP ≥ 100 U/ml), and "middle-C" (neither low/low-C nor high/high-C). Baseline plasma TNF level, serum infliximab level, and disease activity were compared between the three classes. Baseline RF and anti-CCP titers showed significant correlations with baseline TNF and infliximab levels in weeks 2-14. Comparison of the three classes showed that baseline TNF level was lowest in the low/low-C group and highest in the high/high-C group (median 0.73 versus 1.15 pg/ml), that infliximab levels at week 14 were highest in the low/low-C group and lowest in the high/high-C group (median 1.0 versus 0.1 μg/ml), and that Disease Activity Score in 28 joints based on C-reactive protein at week 14 was lowest in the low/low-C group and highest in the high/high-C group (median 3.17 versus 3.82). A similar correlation was observed at week 54 in the 3 mg/kg dosing group, but not in the 6 or 10 mg/kg group. Significant decreases in both RF and anti-CCP were observed during infliximab treatment. RF/anti-CCP titers correlated with TNF level. This might explain the association of RF/anti-CCP with infliximab level and clinical response in patients with RA

  14. Uses of monoclonal antibody 8H9

    Science.gov (United States)

    Cheung, Nai-Kong V.

    2013-04-09

    This invention provides a composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a suitable carrier. This invention provides a pharmaceutical composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a pharmaceutically acceptable carrier. This invention also provides an antibody other than the monoclonal antibody 8H9 comprising the complementary determining regions of monoclonal antibody 8H9 or a derivative thereof, capable of binding to the same antigen as the monoclonal antibody 8H9. This invention provides a substance capable of competitively inhibiting the binding of monoclonal antibody 8H9. This invention also provides an isolated scFv of monoclonal antibody 8H9 or a derivative thereof. This invention also provides the 8H9 antigen. This invention also provides different uses of the monoclonal antibody 8H9 or its derivative.

  15. Biodistribution of 99mTc-labeled anti-human epidermal growth factor receptor (EGF-R) humanized monoclonal antibody h-R3 in a xenograft model of human lung adenocarcinoma

    International Nuclear Information System (INIS)

    Morales-Morales, Alejo; Duconge, Jorge; Caballero-Torres, Idania; Nunez-Gandolff, Gilda; Fernandez, Eduardo; Iznaga-Escobar, Normando

    1999-01-01

    The anti-human epidermal growth factor receptor (EGF-R) humanized monoclonal antibody (MAb) h-R3 is an (IgG 1 ), which binds to an extracellular domain of EGF-R. It was used to evaluate the biodistribution on nude mice xenografted with H-125 human lung adenocarcinoma cell line. Results were compared with its murine version of the MAb ior-egf/r3. Twenty-one athymic female 4NMRI nu/nu mice were injected intraperitoneally with 10 μg/100 μCi of 99m Tc-labeled MAbs. Immunoreactivity of 99m Tc-labeled MAbs were measured by enzyme-linked immunosorbent assay (ELISA) on H-125 cell line and the immunoreactive fractions was determined by the Lindmo method. Among all organs, significant accumulation was found in serum (27.05 ± 2.08 %ID/g) and tumor (3.903 ± 0.89 %ID/g) at 4 h after injection. These values decreased to 5.03 ± 0.50 %ID/g and 2.19 ± 0.56 %ID/g for serum and tumor, respectively. The immunoreactive fraction was found to be 0.70, with a correlation coefficient r=0.9984. With the good biodistribution and tumor uptake of the 99m Tc-labeled humanized antibody h-R3, a phase I diagnostic clinical trial of tumor with epithelial origin should be pursued

  16. Biodistribution of {sup 99m}Tc-labeled anti-human epidermal growth factor receptor (EGF-R) humanized monoclonal antibody h-R3 in a xenograft model of human lung adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Morales-Morales, Alejo; Duconge, Jorge; Caballero-Torres, Idania; Nunez-Gandolff, Gilda; Fernandez, Eduardo; Iznaga-Escobar, Normando E-mail: normando@ict.cim.sld.cu

    1999-04-01

    The anti-human epidermal growth factor receptor (EGF-R) humanized monoclonal antibody (MAb) h-R3 is an (IgG{sub 1}), which binds to an extracellular domain of EGF-R. It was used to evaluate the biodistribution on nude mice xenografted with H-125 human lung adenocarcinoma cell line. Results were compared with its murine version of the MAb ior-egf/r3. Twenty-one athymic female 4NMRI nu/nu mice were injected intraperitoneally with 10 {mu}g/100 {mu}Ci of {sup 99m}Tc-labeled MAbs. Immunoreactivity of {sup 99m}Tc-labeled MAbs were measured by enzyme-linked immunosorbent assay (ELISA) on H-125 cell line and the immunoreactive fractions was determined by the Lindmo method. Among all organs, significant accumulation was found in serum (27.05 {+-} 2.08 %ID/g) and tumor (3.903 {+-} 0.89 %ID/g) at 4 h after injection. These values decreased to 5.03 {+-} 0.50 %ID/g and 2.19 {+-} 0.56 %ID/g for serum and tumor, respectively. The immunoreactive fraction was found to be 0.70, with a correlation coefficient r=0.9984. With the good biodistribution and tumor uptake of the {sup 99m}Tc-labeled humanized antibody h-R3, a phase I diagnostic clinical trial of tumor with epithelial origin should be pursued.

  17. Down-titration and discontinuation strategies of tumor necrosis factor-blocking agents for rheumatoid arthritis in patients with low disease activity.

    Science.gov (United States)

    van Herwaarden, Noortje; den Broeder, Alfons A; Jacobs, Wilco; van der Maas, Aatke; Bijlsma, Johannes W J; van Vollenhoven, Ronald F; van den Bemt, Bart J F

    2014-09-29

    Anti-tumor necrosis factor (TNF) agents are effective in treating patients with rheumatoid arthritis (RA), but they are associated with (dose-dependent) adverse effects and high costs. To prevent overtreatment, several trials have assessed the effectiveness of down-titration compared with continuation of the standard dose. To evaluate the benefits and harms of down-titration (dose reduction, discontinuation or disease activity guided dose tapering) of anti-TNF agents (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) on disease activity, functioning, costs, safety and radiographic damage compared with usual care in patients with RA and low disease activity. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 8, 2013; Ovid MEDLINE (1946 to 8 September 2013); EMBASE (1947 to 8 September 2013); Science Citation Index (Web of Science); and conference proceedings of the American College of Rheumatology (2005 to 2012) and European League against Rheumatism (2005 to 2013). We contacted authors of the seven included studies to ask for additional information on their study; five responded. Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing down-titration (dose reduction, discontinuation, disease activity-guided dose tapering) of anti-TNF agents (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab) to usual care/no down-titration in patients with RA and a low disease activity state. Two review authors independently selected studies, assessed risk of bias and extracted data. Six RCTs and one CCT (total 1203 participants), reporting anti-TNF down-titration, were included. Three studies (559 participants) reported anti-TNF dose reduction compared with anti-TNF continuation. Five studies (732 participants) reported anti-TNF discontinuation compared with anti-TNF continuation (two studies assessed both anti-TNF discontinuation and dose reduction), and one study assessed disease activity

  18. Treatment of therapy-resistant perineal metastatic Crohn's disease after proctectomy using anti-tumor necrosis factor chimeric monoclonal antibody, cA2 - Report of two cases

    NARCIS (Netherlands)

    van Dullemen, HM; de Jong, E; Slors, F; Tytgat, GNJ; van Denventer, SJH

    PURPOSE: Two young females with well-documented Crohn's disease and nonhealing perineal wounds following proctectomy compatible with "metastatic Crohn's disease" are described, We hypothesized that metastatic Crohn's disease would be a tumor necrosis factor-dependent inflammatory-reaction and have

  19. Tumor imaging with monoclonal antibodies

    International Nuclear Information System (INIS)

    Haisma, H.; Hilgers, J.

    1987-01-01

    Many monoclonal antibodies directed against tumor-associated antigens have been identified, but so far none of these are tumor specific. Polyclonal and monoclonal antibodies have been used for imaging of a wide variety of tumors with success. Radiolabeling of antibody is usually done with iodine isotopes of which 123 I is the best candidate for radioimmunodetection purposes. The labeling of antibodies through chelates makes it possible to use metal radioisotopes like 111 In, which is the best radioisotope for imaging with monoclonal antibodies due to its favorable half-life of 2.5 days. Usually imaging cannot be performed within 24 h after injection, but clearance of antibody can be increased by using F(ab) 2 of Fab. Another approach is to clear non-bound antibody by a second antibody, directed against the first. The detection limit of immunoimaging is about 2 cm, but will be improved by tomography or SPECT. There is still a high false positive and false negative rate, which makes it impossible to use radioimmunodetection as the only technique for diagnosis of tumors. In combination with other detection techniques, tumor imaging with monoclonal antibodies can improve diagnosis. 44 refs.; 3 tabs

  20. Radiolabeled monoclonal antibodies: a review

    International Nuclear Information System (INIS)

    Toledo e Souza, I.T. de; Okada, H.

    1990-05-01

    Since the description by Kohler and Milstein 1975 of their technique for producing monoclonal antibodies of predefined specificity, it has become a mainstay in most laboratories that utilize immunochemical techniques to study problems in basic, applied or clinical research. Paradoxically, the very success of monoclonal antibodies has generated a literature which is now so vast and scattered that it has become difficult to obtain a perspective. This brief review represents the distillation of many publications relating to the production and use of monoclonaal antibodies as radiopharmaceuticals. Significant advances were made possible in the last few years by combined developments in the fields of tumor-associated antigens and of monoclonal antibodies. In fact monoclonal antibodies against some well defined tumor-associated antigens, has led to significantly greater practical possibilities for producing highly specific radiolabeled antibodies as radiopharmaceuticals for diagnosis and therapy of human tumors. One of the main requirements of this methodology is the availability of stable radiopharmaceutical reagents which after labeling in vivo injection retain the capacity of specific interaction with the defined antigen and their molecular integrity. Since injection into human is the objetive of this kind of study all the specifications of radiopharmaceutical have to be fulfilled e.g. sterility, apirogenicity and absence of toxicity. (author) [pt

  1. Shoulder arthography in rheumatoid arthritis

    International Nuclear Information System (INIS)

    Reinbold, W.D.; Hehne, H.J.; Rau, W.S.; Freiburg Univ.

    1983-01-01

    Shoulder arthrography in a patient with rheumatoid arthritis is performed to differentiate between a rheumatoid flare and limitation of motion secondary to tear in the rotator cuff. Accurate diagnosis is important because of the therapeutic implications. The arthrographic findings characteristic of rheumatoid involvement of the shoulder joint are nodular filling defects of the joint, the subacromial and subdeltoideal bursa in case of rotator cuff tear, irregular capsular attachment, contracted joint space and visualized lymphatic drainage. A dilatation of the biceps tendon sheath has not been shown. (orig.) [de

  2. Cervical Myelopathy in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    N. Mukerji

    2011-01-01

    Full Text Available Involvement of the cervical spine is common in rheumatoid arthritis. Clinical presentation can be variable, and symptoms may be due to neck pain or compressive myeloradiculopathy. We discuss the pathology, grading systems, clinical presentation, indications for surgery and surgical management of cervical myelopathy related to rheumatoid arthritis in this paper. We describe our surgical technique and results. We recommend early consultation for surgical management when involvement of the cervical spine is suspected in rheumatoid arthritis. Even patients with advanced cervical myelopathy should be discussed for surgical treatment, since in our experience improvement in function after surgery is common.

  3. Obesity is the main determinant of insulin resistance more than the circulating pro-inflammatory cytokines levels in rheumatoid arthritis patients.

    Science.gov (United States)

    Castillo-Hernandez, Jesus; Maldonado-Cervantes, Martha Imelda; Reyes, Juan Pablo; Patiño-Marin, Nuria; Maldonado-Cervantes, Enrique; Solorzano-Rodriguez, Claudia; de la Cruz Mendoza, Esperanza; Alvarado-Sanchez, Brenda

    Systemic blockade of TNF-α in Rheumatoid arthritis with insulin resistance seems to produce more improvement in insulin sensitivity in normal weight patients with Rheumatoid arthritis than in obese patients with Rheumatoid arthritis, suggesting that systemic-inflammation and obesity are independent risk factors for insulin resistance in Rheumatoid arthritis patients. To evaluate the insulin resistance in: normal weight patients with Rheumatoid arthritis, overweight patients with Rheumatoid arthritis, obese Rheumatoid arthritis patients, and matched control subjects with normal weight and obesity; and its association with major cytokines involved in the pathogenesis of the disease. Assessments included: body mass index, insulin resistance by Homeostasis Model Assessment, ELISA method, and enzymatic colorimetric assay. Outstanding results from these studies include: (1) In Rheumatoid arthritis patients, insulin resistance was well correlated with body mass index, but not with levels of serum cytokines. In fact, levels of cytokines were similar in all Rheumatoid arthritis patients, regardless of being obese, overweight or normal weight (2) Insulin resistance was significantly higher in Rheumatoid arthritis with normal weight than in normal weight (3) No significant difference was observed between insulin resistances of Rheumatoid arthritis with obesity and obesity (4) As expected, levels of circulating cytokines were significantly higher in Rheumatoid arthritis patients than in obesity. Obesity appears to be a dominant condition above inflammation to produce IR in RA patients. The dissociation of the inflammation and obesity components to produce IR suggests the need of an independent therapeutic strategy in obese patients with RA. Copyright © 2017. Published by Elsevier Editora Ltda.

  4. A randomized, phase II study of the anti-insulin-like growth factor receptor type 1 (IGF-1R) monoclonal antibody robatumumab (SCH 717454) in patients with advanced colorectal cancer

    International Nuclear Information System (INIS)

    Lin, Edward H; Lenz, Heinz-Josef; Saleh, Mansoor N; Mackenzie, Mary J; Knost, James A; Pathiraja, Kumudu; Langdon, Ronald B; Yao, Siu-Long; Lu, Brian D

    2014-01-01

    Overexpression of insulin-like growth factor receptor type 1 (IGF-1R) may promote tumor development and progression in some cancer patients. Our objective was to assess tumor uptake of fluorodeoxyglucose by positron-emission tomography in patients with chemotherapy-refractory colorectal cancer treated with an anti-insulin-like growth factor receptor type 1 (anti-IGF-1R) monoclonal antibody, robatumumab. This was a randomized, open-label study with two periods (P1 and P2). Patients were randomized 3:1 into treatment arms R/R and C/R that received, respectively, one cycle of 0.3 mg/kg robatumumab or one or more cycles of second-line chemotherapy in P1, followed in either case by 10 mg/kg robatumumab biweekly in P2. The primary measure of fluorodeoxyglucose uptake was maximum standardized uptake value (SUV max ). The primary endpoint was the proportion of patients in the R/R arm having a mean percent decrease from baseline in SUV max (DiSUV) greater than 20% 12–14 days postdose in P2. Secondary endpoints included Response Evaluation Criteria in Solid Tumors (RECIST)-defined tumor response and pharmacodynamic measures of target engagement. Among 41 patients who were evaluable for the primary endpoint, seven (17%, 95% CI 7%–32%) had DiSUV greater than 20%. Fifty robatumumab-treated patients were evaluable for RECIST-defined tumor response and six (12%) had stable disease lasting greater than or equal to 7 weeks in P2. Pharmacodynamic endpoints indicated target engagement after dosing with 10 mg/kg robatumumab, but not 0.3 mg/kg. The most frequently reported adverse events were fatigue/asthenia, nausea, anorexia, and gastrointestinal disturbances. In this study, few patients with chemotherapy-refractory colorectal cancer appeared to benefit from treatment with the IGF-1R antagonist robatumumab

  5. Monoclonal antibodies technology. Protocols

    International Nuclear Information System (INIS)

    Acevado Castro, B.E.

    1997-01-01

    Full text: Immunization. The first step in preparing useful monoclonal antibodies (MAbs) is to immunize an animal (Balb/c for example) with an appropriate antigen. Methods (only for soluble antigen): Solubilize selected antigen in Phosphate buffer solution (PBS) at pH 7.2-7.4, ideally at a final concentration per animal between 10 to 50 μg/ml. It is recommended that the antigen under consideration be incorporated into the emulsion adjuvants in 1:1 volumetric relation. We commonly use Frend's adjuvant (FA) to prepared immunized solution. The first immunization should be prepared with complete FA, and the another could be prepared with incomplete FA. It is recommended to inject mice with 0.2 ml intraperitoneal (ip) or subcutaneous (sc). Our experience suggests the sc route is the preferred route. A minimum protocol for immunizing mice to generate cells for preparing hybridomas is s follows: immunize sc on day 0, boost sc on day 21, take a trial bleeding on day 26; if antibody titters are satisfactory, boost ip on day 35 with antigen only, and remove the spleen to obtain cells for fusion on day 38. Fusion protocol. The myeloma cell line we are using is X63 Ag8.653. At the moment of fusion myeloma cells need a good viability (at least a 95%). 1. Remove the spleen cells from immunized mice using sterile conditions. An immune spleen should yield between 7 a 10x10 7 nucleated cells. 2. Place the spleen in 20 ml of serum-free RPMI 1640 in a Petri dish. Using a needle and syringe, inject the spleen with medium to distend and disrupt the spleen stroma and free the nucleated cells. 3. Flush the cell suspension with a Pasteur pipet to disperse clumps of cells. 4. Centrifuge the spleen cell suspension at 250g for 10 min. Resuspend the pellet in serum-free RPMI 1640. Determine cell concentration using Neuhabuer chamber. 5. Mix the myeloma cells and spleen cells in a conical 50-ml tube in serum-free RPMI 1640, 1 x10 7 spleen cells to 1x10 6 myeloma cells (ratio 10:1). Centrifuge

  6. Rheumatoid Arthritis Educational Video Series

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    Full Text Available ... Arthritis and Health-related Quality of Life Rehabilitation Management for Rheumatoid Arthritis Patients Rehabilitation of Older Adult ... Sheets Benefits and Risks of Opioids in Arthritis Management How to Give a Subcutaneous Injection Connect With ...

  7. Rheumatoid Arthritis Educational Video Series

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    Full Text Available ... and what other conditions are associated with RA. Learning more about your condition will allow you to ... Older Adult Patients with Arthritis Complementary and Alternative Medicine for Patients with Rheumatoid Arthritis Yoga for Arthritis ...

  8. Rheumatoid Arthritis Educational Video Series

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    Full Text Available ... Arthritis Managing Your Arthritis Managing Chronic Pain and Depression in Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health- ... on this website. Copyright Johns Hopkins Arthritis Center © 2018 Patient Privacy Johns Hopkins Rheumatology

  9. Rheumatoid Arthritis Educational Video Series

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    Full Text Available ... you learn more about Rheumatoid Arthritis (RA). You will learn how the diagnosis of RA is made, ... associated with RA. Learning more about your condition will allow you to take a more active role ...

  10. Rheumatoid arthritis and hand surgery

    DEFF Research Database (Denmark)

    Peretz, Anne Sofie Rosenborg; Madsen, Ole Rintek; Brogren, Elisabeth

    2017-01-01

    Rheumatoid arthritis results in characteristic deformities of the hand. Medical treatment has undergone a remarkable development. However, not all patients achieve remission or tolerate the treatment. Patients who suffer from deformities and persistent synovitis may be candidates for hand surgery...

  11. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Management for Rheumatoid Arthritis Patients Rehabilitation of Older Adult Patients with Arthritis Complementary and Alternative Medicine for ... Patient Update Transitioning the JRA Patient to an Adult Rheumatologist Drug Information for Patients Arthritis Drug Information ...

  12. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Arthritis Managing Chronic Pain and Depression in Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health-related Quality of ... Hopkins Rheumatology Arthritis Center Lupus Center Lyme Disease Clinical Research Center Myositis Center Scleroderma Center Sjogren’s Syndrome ...

  13. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... She is a critical member of our patient care team. Managing Your Arthritis Managing Your Arthritis Managing Chronic Pain and Depression in Arthritis Nutrition & Rheumatoid Arthritis Arthritis and Health- ...

  14. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... of Body Weight in Osteoarthritis Educational Videos for Patients Rheumatoid Arthritis Educational Video Series Psoriatic Arthritis 101 ... Patient to an Adult Rheumatologist Drug Information for Patients Arthritis Drug Information Sheets Benefits and Risks of ...

  15. Fetal Programming in Rheumatoid Arthritis

    NARCIS (Netherlands)

    F.D.O. de Steenwinkel (Florentien)

    2013-01-01

    markdownabstract__Abstract__ Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory, autoimmune disease mainly affecting synovial tissues, which can lead to severe morbidity and progressive joint destruction resulting in deformations and disability. Other important outcomes include

  16. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Arthritis and Health-related Quality of Life Rehabilitation Management for Rheumatoid Arthritis Patients Rehabilitation of Older Adult ... Sheets Benefits and Risks of Opioids in Arthritis Management How to Give a Subcutaneous Injection Rheumatology Course ...

  17. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... a more active role in your care. The information in these videos should not take the place of any advice you ... Management for Rheumatoid Arthritis Patients Rehabilitation of Older Adult ...

  18. Generation of monoclonal antibodies against peptidylarginine deiminase 2 (PAD2) and development of a PAD2-specific enzyme-linked immunosorbent assay

    DEFF Research Database (Denmark)

    Damgaard, Dres; Palarasah, Yaseelan; Skjødt, Karsten

    2014-01-01

    The enzyme peptidylarginine deiminase 2 (PAD2) has been associated with inflammatory diseases, such as rheumatoid arthritis and neurodegenerative diseases including multiple sclerosis. To investigate the association of various diseases with extracellular PAD2, we raised monoclonal antibodies (m......Abs) against rabbit PAD2 and evaluated their cross-reactivity with human PAD2 by indirect enzyme-linked immunosorbent assay (ELISA), western blotting and immunohistological staining of inflamed synovial tissue. Moreover, we established a sandwich ELISA detecting human PAD2, based on two different monoclonal...... diseases....

  19. Self-efficacy for exercise, more than disease-related factors, is associated with objectively assessed exercise time and sedentary behaviour in rheumatoid arthritis.

    Science.gov (United States)

    Huffman, K M; Pieper, C F; Hall, K S; St Clair, E W; Kraus, W E

    2015-01-01

    Until recently, reports of physical activity in rheumatoid arthritis (RA) were limited to self-report methods and/or leisure-time physical activity. Our objectives were to assess, determine correlates of, and compare to well-matched controls both exercise and sedentary time in a typical clinical cohort of RA. Persons with established RA (seropositive or radiographic erosions; n = 41) without diabetes or cardiovascular disease underwent assessments of traditional and disease-specific correlates of physical activity and 7 days of triaxial accelerometry. Twenty-seven age, gender, and body mass index (BMI)-matched controls were assessed. For persons with RA, objectively measured median (25th-75th percentile) exercise time was 3 (1-11) min/day; only 10% (n = 4) of participants exercised for ≥ 30 min/day. Time spent in sedentary activities was 92% (89-95%). Exercise time was not related to pain but was inversely related to disease activity (r = -0.3, p self-efficacy for endurance activity (r = 0.4, p self-efficacy for endurance activity (r = -0.4, p self-efficacy for physical activity but similar amounts of exercise and sedentary time. For persons with RA and without diabetes or cardiovascular disease, time spent in exercise was well below established guidelines and activity patterns were predominantly sedentary. For optimal care in RA, in addition to promoting exercise, clinicians should consider assessing sedentary behaviour and self-efficacy for exercise. Future interventions might determine whether increased self-efficacy can increase physical activity in RA.

  20. [Effects of grain-sized moxibustion from 7 am to 9 am on circadian rhythm of inflammatory factor IL-6 in rats with rheumatoid arthritis].

    Science.gov (United States)

    Ma, Wenbin; Liu, Xuguang; Qin, Yong; Zhou, Haiyan; Yang, Xin

    2016-04-01

    To explore the rhythm regulatory mechanism of interleukin-6 (IL-6) in the process of moxibustion for rheumatoid arthritis (RA). A total of 144 Sprague-Dawley (SD) rats were randomly divided into a blank group, a model group, a moxibustion group, a sham operation group, an operation group, an operation+moxibustion group, 24 rats in each one. Each group was divided into 4 time points (0:00 am, 6:00' am, 12:00 am, 6:00 pm), 6 rats in each time point. The Light-Dark 12 : 12 was given in all rats for light-dark cycle. Except the blank group, rats in the remaining groups were treated with intracutaneous injection of freund's complete adjuvant at right-side foot to establish the model of RA. After the model establishment, bilateral adrenal, glands were removed in the operation group and operation + moxibustion group, while those in the sham operation group were not removed with identical operation procedure. Rats in the moxibustion group and operation + moxibustion group were treated with grain-sized moxibustion from 7:00 am to 9:00 am at "Shenshu" (BL 23) and "Zusanli" (ST 36) once everyday, 6 times were taken as one session and 3 sessions were required tatclly, while rats in the remaining groups received identical fixation without moxibustion. The general health state and foot volume of rats were measured before model establishment, after establishment and after treatment. After treatment, rats were sacrificed at each time point to collect the blood sample and measure the content of IL-6 by using enzymne-immunoassay method. Compared with the blank group, the foot swelling in the model group was obviously increased (Pcircadian rhythm (Pcircadian. rhythm (Pcircadian rhythm (P circadian rhythm in RA rats; with the complete hypothalamic-pituitary-adrenal axis, moxibustion is likely to regulate the circadian rhythm of IL-6 to play an important role of anti-inflammatory effect in RA rats.

  1. Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-alpha, Oncostatin M and response to biologic therapies.

    LENUS (Irish Health Repository)

    Moran, Ellen M

    2009-01-01

    INTRODUCTION: The aim of this study was to examine IL-17A in patients, following anti-TNF-alpha therapy and the effect of IL-17A on matrix turnover and cartilage degradation. METHODS: IL-17A expression was examined by ELISA and immunohistology in the rheumatoid arthritis (RA) joints. RA whole synovial tissue explant (RA ST), primary synovial fibroblasts (RASFC), human cartilage and chondrocyte cultures were stimulated with IL-17A +\\/- TNF-alpha and Oncostatin M (OSM). Matrix metalloproteinase (MMP) and tissue inhibitor (TIMP-1) were assessed by ELISA and zymography. Cartilage proteoglycan release was assessed histologically by Safranin-O staining. Clinical parameters, IL-17A, MMP\\/TIMP were assessed in patients pre\\/post biologic therapy. RESULTS: IL-17A levels were higher in RA vs osteoarthritis (OA)\\/normal joints (P < 0.05). IL-17A up-regulated MMP-1, -2, -9, and -13 in RA ST, RASFC, cartilage and chondrocyte cultures (P < 0.05). In combination with TNF-alpha and OSM, IL-17A shifted the MMP:TIMP-1 ratio in favor of matrix degradation (all P < 0.05). Cartilage proteoglycan depletion in response to IL-17A was mild; however, in combination with TNF-alpha or OSM showed almost complete proteoglycan depletion. Serum IL-17A was detected in 28% of patients commencing biologic therapy. IL-17A negative patients demonstrated reductions post therapy in serum MMP1\\/TIMP4, MMP3\\/TIMP1 and MMP3\\/TIMP4 ratios and an increase in CS846 (all P < 0.05). No significant changes were observed in IL-17A positive patients. CONCLUSIONS: IL-17A is produced locally in the inflamed RA joint. IL-17A promotes matrix turnover and cartilage destruction, especially in the presence of other cytokines, mimicking the joint environment. IL-17A levels are modulated in vivo, following anti-TNF therapy, and may reflect changes in matrix turnover.

  2. Combined anti-tumor necrosis factor-α therapy and DMARD therapy in rheumatoid arthritis patients reduces inflammatory gene expression in whole blood compared to DMARD therapy alone

    Directory of Open Access Journals (Sweden)

    Carl K Edwards

    2012-12-01

    Full Text Available Periodic assessment of gene expression for diagnosis and monitoring in rheumatoid arthritis (RA may provide a readily available and useful method to detect subclinical disease progression and follow responses to therapy with disease modifying anti-rheumatic agents (DMARDs or anti-TNF-α therapy. We used quantitative real-time PCR to compare peripheral blood gene expression profiles in active ("unstable" RA patients on DMARDs, stable RA patients on DMARDs, and stable RA patients treated with a combination of a DMARD and an anti-TNF-α agent (infliximab or etanercept to healthy human controls. The expression of 48 inflammatory genes were compared between healthy controls (N=122, unstable DMARD patients (N=18, stable DMARD patients (N=26, and stable patients on combination therapy (N=20. Expression of 13 genes was very low or undetectable in all study groups. Compared to healthy controls, patients with unstable RA on DMARDs exhibited increased expression of 25 genes, stable DMARD patients exhibited increased expression of 14 genes and decreased expression of five genes, and combined therapy patients exhibited increased expression of six genes and decreased expression of 10 genes. These findings demonstrate that active RA is associated with increased expression of circulating inflammatory markers whereas increases in inflammatory gene expression are diminished in patients with stable disease on either DMARD or anti-TNF-α therapy. Furthermore, combination DMARD and anti-TNF-α therapy is associated with greater reductions in circulating inflammatory gene expression compared to DMARD therapy alone. These results suggest that assessment of peripheral blood gene expression may prove useful to monitor disease progression and response to therapy.

  3. Polymorphisms in STAT-4, IL-10, PSORS1C1, PTPN2 and MIR146A genes are associated differently with prognostic factors in Italian patients affected by rheumatoid arthritis.

    Science.gov (United States)

    Ciccacci, C; Conigliaro, P; Perricone, C; Rufini, S; Triggianese, P; Politi, C; Novelli, G; Perricone, R; Borgiani, P

    2016-11-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease resulting in chronic inflammation of the synovium and consequent cartilage and bone erosion. RA is associated strongly with the presence of rheumatoid factor (RF), and consists of clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and -negative patients. This study was designed to evaluate whether relevant single nucleotide polymorphisms (SNPs) associated with RA and other autoimmune disorders are related to RF, ACPA and clinical phenotype in a cohort of biologic drugs naive Italian RA patients; 192 RA patients and 278 age-matched healthy controls were included. Clinical and laboratory data were registered. We analysed a total of 12 single nucleotide polymorphisms (SNPs) in signal transducer and activator of transcription-4 (STAT-4), interleukin (IL)-10, psoriasis susceptibility 1 candidate 1 (PSORS1C1), protein tyrosine phosphatase, non-receptor type 2 (PTPN2), endoplasmic reticulum aminopeptidase 1 (ERAP1), tumour necrosis factor receptor-associated 3 interacting protein 2 (TRAF3IP2) and microRNA 146a (MIR146A) genes by allelic discrimination assays. Case-control association studies and genotype/phenotype correlation analyses were performed. A higher risk to develop RA was observed for rs7574865 in the STAT-4 gene, while the rs1800872 in the IL-10 gene showed a protective effect. The presence of RF was associated significantly with rs1800872 variant in IL-10, while rs2910164 in MIR146A was protective. ACPA were associated significantly with rs7574865 in STAT-4. The SNP rs2233945 in the PSORS1C1 gene was protective regarding the presence of bone erosions, while rs2542151 in PTPN2 gene was associated with joint damage. Our results confirm that polymorphisms in STAT-4 and IL-10 genes confer susceptibility to RA. For the first time, we described that SNPs in PSORS1C1, PTPN2 and MIR146A genes were associated differently with a severe disease phenotype in terms of autoantibody status and

  4. Polymorphisms in STAT‐4, IL‐10, PSORS1C1, PTPN2 and MIR146A genes are associated differently with prognostic factors in Italian patients affected by rheumatoid arthritis

    Science.gov (United States)

    Ciccacci, C.; Conigliaro, P.; Rufini, S.; Triggianese, P.; Politi, C.; Novelli, G.; Perricone, R.; Borgiani, P.

    2016-01-01

    Summary Rheumatoid arthritis (RA) is a systemic autoimmune disease resulting in chronic inflammation of the synovium and consequent cartilage and bone erosion. RA is associated strongly with the presence of rheumatoid factor (RF), and consists of clinical subsets of anti‐citrullinated protein antibody (ACPA)‐positive and ‐negative patients. This study was designed to evaluate whether relevant single nucleotide polymorphisms (SNPs) associated with RA and other autoimmune disorders are related to RF, ACPA and clinical phenotype in a cohort of biologic drugs naive Italian RA patients; 192 RA patients and 278 age‐matched healthy controls were included. Clinical and laboratory data were registered. We analysed a total of 12 single nucleotide polymorphisms (SNPs) in signal transducer and activator of transcription‐4 (STAT‐4), interleukin (IL)‐10, psoriasis susceptibility 1 candidate 1 (PSORS1C1), protein tyrosine phosphatase, non‐receptor type 2 (PTPN2), endoplasmic reticulum aminopeptidase 1 (ERAP1), tumour necrosis factor receptor‐associated 3 interacting protein 2 (TRAF3IP2) and microRNA 146a (MIR146A) genes by allelic discrimination assays. Case‐control association studies and genotype/phenotype correlation analyses were performed. A higher risk to develop RA was observed for rs7574865 in the STAT‐4 gene, while the rs1800872 in the IL‐10 gene showed a protective effect. The presence of RF was associated significantly with rs1800872 variant in IL‐10, while rs2910164 in MIR146A was protective. ACPA were associated significantly with rs7574865 in STAT‐4. The SNP rs2233945 in the PSORS1C1 gene was protective regarding the presence of bone erosions, while rs2542151 in PTPN2 gene was associated with joint damage. Our results confirm that polymorphisms in STAT‐4 and IL‐10 genes confer susceptibility to RA. For the first time, we described that SNPs in PSORS1C1, PTPN2 and MIR146A genes were associated differently with a severe disease

  5. Platelet-activating factor stimulation of tyrosine kinase and its relationship to phospholipase C in rabbit platelets: Studies with genistein and monoclonal antibody to phosphotyrosine

    International Nuclear Information System (INIS)

    Dhar, A.; Paul, A.K.; Shukla, S.D.

    1990-01-01

    Platelet-activating factor (PAF) is a proinflammatory lipid that has platelet-stimulating property. PAF receptor-coupled activation of phosphoinositide-specific phospholipase C (PLC) and phosphorylation of several proteins has already been established in our laboratory. To investigate further the molecular mechanism and relationship between activation of PLC and protein phosphorylation, we have used Genistein (a putative inhibitor of tyrosine-specific protein kinases), phosphotyrosine antibody, and phosphoamino acid analysis to probe the involvement of tyrosine kinase in this process. Washed rabbit platelets were loaded with myo-[2-3H]inositol and challenged with PAF (100 nM) after pretreatment with Genistein. PLC-mediated production of radioactive inositol monophosphate, inositol diphosphate, and inositol triphosphate was monitored. PAF alone caused stimulation of PLC activity [( 3H]inositol triphosphate production), whereas pretreatment with Genistein (0.5 mM) diminished PAF-stimulated PLC activity to basal level. Genistein also blocked PAF-stimulated platelet aggregation at this dose. In contrast to Genistein, staurosporine which inhibits protein kinase C, potentiated PAF-stimulated [3H]inositol triphosphate production. Genistein substantially inhibited the combined effects of staurosporine and PAF on inositol triphosphate production. Genistein also reduced PAF-induced phosphorylation of Mr 20,000 and 50,000 proteins. Phorbol 12-myristate 13-acetate-induced Mr 40,000 protein phosphorylation was also affected by Genistein. The above results suggested that Genistein inhibited tyrosine kinase at an early stage of signal transduction by inhibiting PLC. This, in turn, decreased the activation of protein kinase C and, therefore, caused a reduction in Mr 40,000 protein phosphorylation

  6. Aggregates in monoclonal antibody manufacturing processes.

    Science.gov (United States)

    Vázquez-Rey, María; Lang, Dietmar A

    2011-07-01

    Monoclonal antibodies have proved to be a highly successful class of therapeutic products. Large-scale manufacturing of pharmaceutical antibodies is a complex activity that requires considerable effort in both process and analytical development. If a therapeutic protein cannot be stabilized adequately, it will lose partially or totally its therapeutic properties or even cause immunogenic reactions thus potentially further endangering the patients' health. The phenomenon of protein aggregation is a common issue that compromises the quality, safety, and efficacy of antibodies and can happen at different steps of the manufacturing process, including fermentation, purification, final formulation, and storage. Aggregate levels in drug substance and final drug product are a key factor when assessing quality attributes of the molecule, since aggregation might impact biological activity of the biopharmaceutical. In this review it is analyzed how aggregates are formed during monoclonal antibody industrial production, why they have to be removed and the manufacturing process steps that are designed to either minimize or remove aggregates in the final product. Copyright © 2011 Wiley Periodicals, Inc.

  7. Bone marrow dosimetry for monoclonal antibody therapy

    International Nuclear Information System (INIS)

    Bigler, R.E.; Zanzonico, P.B.; Leonard, R.

    1986-01-01

    Immunoglobulins must permeate through the basement membrane of capillaries in order to enter the extracellular space (ECS) of tissue. Since the process is quite slow, the blood plasma activity in various organs contributes considerably to the radiation dose of the dose-limiting tissues. In bone marrow the basement membrane is absent and the blood circulation is functionally open. Therefore, blood plasma and marrow ECS maintain equal concentrations of labeled immunoglobulins. A combination of factors including intravenous administration, slow absorption into most tissues, slow breakdown and elimination of labeled immunoglobulin, and rapid entry into bone marrow ECS as well as known radiosensitivity of marrow led the authors to expect this tissue would prove to be the primary tissue at risk for systemic monoclonal antibody therapy. They have developed and applied in a Phase I clinical study of 131 I labeled CEA antibody a procedure for estimation of radiation dose to red bone marrow. Serieal measurements of blood plasma and total body retention are carried out. Binding of labeled antibody to the cellular components of blood is verified to be very low. They have observed bone marrow depression at doses greater than 400 rad. If no special procedures are used to reconstitute marrow after radiation treatment, this level represents a much greater than generally recognized limitation to radiolabeled monoclonal antibody therapy. 25 references, 4 tables

  8. Rheumatoid arthritis and pulmonary nodules: An unexpected final diagnosis.

    Science.gov (United States)

    Zurita Prada, Pablo Antonio; Urrego Laurín, Claudia Lía; Assyaaton Bobo, Sow; Faré García, Regina; Estrada Trigueros, Graciliano; Gallardo Romero, José Manuel; Borrego Pintado, Maria Henar

    We report the case of a 50-year-old female smoker with an 11-year history of seropositive rheumatoid arthritis (rheumatoid factor and anti-cyclic citrullinated peptide antibodies) receiving triple therapy. She developed pulmonary nodules diagnosed as Langerhans cell histiocytosis by lung biopsy. We found no reported cases of the coexistence of these two diseases. Smoking abstinence led to radiologic resolution without modifying the immunosuppressive therapy. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  9. Phase I study of GC1008 (fresolimumab: a human anti-transforming growth factor-beta (TGFβ monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    John C Morris

    Full Text Available In advanced cancers, transforming growth factor-beta (TGFβ promotes tumor growth and metastases and suppresses host antitumor immunity. GC1008 is a human anti-TGFβ monoclonal antibody that neutralizes all isoforms of TGFβ. Here, the safety and activity of GC1008 was evaluated in patients with advanced malignant melanoma and renal cell carcinoma.In this multi-center phase I trial, cohorts of patients with previously treated malignant melanoma or renal cell carcinoma received intravenous GC1008 at 0.1, 0.3, 1, 3, 10, or 15 mg/kg on days 0, 28, 42, and 56. Patients achieving at least stable disease were eligible to receive Extended Treatment consisting of 4 doses of GC1008 every 2 weeks for up to 2 additional courses. Pharmacokinetic and exploratory biomarker assessments were performed.Twenty-nine patients, 28 with malignant melanoma and 1 with renal cell carcinoma, were enrolled and treated, 22 in the dose-escalation part and 7 in a safety cohort expansion. No dose-limiting toxicity was observed, and the maximum dose, 15 mg/kg, was determined to be safe. The development of reversible cutaneous keratoacanthomas/squamous-cell carcinomas (4 patients and hyperkeratosis was the major adverse event observed. One malignant melanoma patient achieved a partial response, and six had stable disease with a median progression-free survival of 24 weeks for these 7 patients (range, 16.4-44.4 weeks.GC1008 had no dose-limiting toxicity up to 15 mg/kg. In patients with advanced malignant melanoma and renal cell carcinoma, multiple doses of GC1008 demonstrated acceptable safety and preliminary evidence of antitumor activity, warranting further studies of single agent and combination treatments.Clinicaltrials.gov NCT00356460.

  10. Risk of Japanese carriers of hyperphosphorylated paratarg-7, the first autosomal-dominantly inherited risk factor for hematological neoplasms, to develop monoclonal gammopathy of undetermined significance and multiple myeloma.

    Science.gov (United States)

    Grass, Sandra; Iida, Shinsuke; Wikowicz, Aleksandra; Preuss, Klaus-Dieter; Inagaki, Atsushi; Shimizu, Kazuyuki; Ziepert, Marita; Ueda, Ryuzo; Pfreundschuh, Michael

    2011-03-01

    Hyperphosphorylated paratarg-7 (pP-7) is a frequent target of paraproteins in German patients with monoclonal gammopathy of undetermined significance (MGUS)/multiple myeloma (MM). The frequency of MGUS/MM is lower in Japan than in Europe. As pP-7, the first molecularly defined autosomal-dominant risk factor for any hematological neoplasm, is inherited in a dominant fashion, we determined the incidence of the pP-7 carrier state in a Japanese population, and compared the frequency of pP-7-specific paraproteins and the pP-7 carrier state in Japanese and German patients with MGUS/MM. Peripheral blood from 111 Japanese patients with MGUS/MM and 278 healthy blood donors was analyzed for the pP-7 carrier state by isoelectric focusing and for pP-7-specific antibodies by ELISA. The Japanese group was compared with 252 German MGUS/MM patients and 200 healthy controls. Five of 111 (4.5%) Japanese and 35/252 (13.9%) German IgA/IgG MGUS/MM patients had a pP-7-specific paraprotein (P=0.009). The prevalence of healthy pP-7 carriers in the Japanese study group was 1/278 (0.36%), whereas it was 4/200 in the German group (P=0.166). The relative risk for pP-7 carriers developing MGUS/MM had an odds ratio of 13.1 in the Japanese and 7.9 in the German group. In conclusion, the fraction of pP-7 carriers with a pP-7-specific paraprotein is lower among Japanese than in German patients with MGUS/MM, but pP-7 carriers in both ethnic groups have a high risk of developing MGUS/MM. © 2011 Japanese Cancer Association.

  11. Physiotherapy in Rheumatoid Arthritis

    Science.gov (United States)

    Kavuncu, Vural; Evcik, Deniz

    2004-01-01

    Rheumatoid arthritis (RA) is a chronic and painful clinical condition that leads to progressive joint damage, disability, deterioration in quality of life, and shortened life expectancy. Even mild inflammation may result in irreversible damage and permanent disability. The clinical course according to symptoms may be either intermittent or progressive in patients with RA. In most patients, the clinical course is progressive, and structural damage develops in the first 2 years. The aim of RA management is to achieve pain relief and prevent joint damage and functional loss. Physiotherapy and rehabilitation applications significantly augment medical therapy by improving the management of RA and reducing handicaps in daily living for patients with RA. In this review, the application of physiotherapy modalities is examined, including the use of cold/heat applications, electrical stimulation, and hydrotherapy. Rehabilitation treatment techniques for patients with RA such as joint protection strategies, massage, exercise, and patient education are also presented. PMID:15266230

  12. Evaluación de un método de aglutinación con látex para la detección de factor reumatoide Evaluation of a latex agglutination method for the detection of rheumatoid factor

    Directory of Open Access Journals (Sweden)

    Ana M. Guerreiro Hernández

    2008-04-01

    Full Text Available Se evaluó un método de aglutinación con látex de producción nacional (Centis, para la detección de factor reumatoide, empleándose como procedimiento de referencia un ensayo turbidimétrico con látex (Spin React, España en un grupo de pacientes con artritis reumatoide. Los resultados obtenidos en el método evaluado: sensibilidad 93 %; especificidad 80 %; valor predictivo positivo 97,6 %; valor predictivo negativo 57,1 %; y un límite de detección de 15 UI/mL, indican su calidad y utilidad.An agglutination method with latex of national production (Centis was evaluated to detect the rheumatoid factor by using a turbidimetric assay with latex (Spin React, Spain as a reference procedure in a group of patients with rheumatoid arthritis. The results obtained in the evaluated method (sensitivity 93 %, specificity 80 %, positive predictive value 97.6 %, negative predictive value 57.1 %, and a detection limit of 15 UI/mL showed its quality and usefulness.

  13. A rheumatoid arthritis study by Fourier transform infrared spectroscopy

    Science.gov (United States)

    Carvalho, Carolina S.; Silva, Ana Carla A.; Santos, Tatiano J. P. S.; Martin, Airton A.; dos Santos Fernandes, Ana Célia; Andrade, Luís E.; Raniero, Leandro

    2012-01-01

    Rheumatoid arthritis is a systemic inflammatory disease of unknown causes and a new methods to identify it in early stages are needed. The main purpose of this work is the biochemical differentiation of sera between normal and RA patients, through the establishment of a statistical method that can be appropriately used for serological analysis. The human sera from 39 healthy donors and 39 rheumatics donors were collected and analyzed by Fourier Transform Infrared Spectroscopy. The results show significant spectral variations with p<0.05 in regions corresponding to protein, lipids and immunoglobulins. The technique of latex particles, coated with human IgG and monoclonal anti-CRP by indirect agglutination known as FR and CRP, was performed to confirm possible false-negative results within the groups, facilitating the statistical interpretation and validation of the technique.

  14. Systemic immune markers characterizing early stages of rheumatoid arthritis

    NARCIS (Netherlands)

    Chalan, Paulina Luiza

    2016-01-01

    Rheumatoid arthritis is a chronic autoimmune disease occurring in ~1% of the world population. The main feature of the disease is ongoing joint inflammation, caused by immune cells and their soluble factors, leading to irreversible bone erosions and cartilage damage. Early treatment can halt

  15. Monitoring anti-TNFalpha treatment in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Haavardsholm, E A; Østergaard, Mikkel; Hammer, H B

    2009-01-01

    OBJECTIVES: To evaluate the responsiveness of magnetic resonance imaging (MRI) and ultrasonography (US) compared with conventional measures of disease activity and structural damage in patients with rheumatoid arthritis (RA) during the first year of treatment with anti-tumour necrosis factor alpha...

  16. Rheumatoid Arthritis, Immunosenescence and the Hallmarks of Aging

    NARCIS (Netherlands)

    Chalan, Paulina; van den Berg, Anke; Kroesen, Bart-Jan; Brouwer, Liesbeth; Boots, Annemieke

    2015-01-01

    Age is the most important risk factor for the development of infectious diseases, cancer and chronic inflammatory diseases including rheumatoid arthritis (RA). The very act of living causes damage to cells. A network of molecular, cellular and physiological maintenance and repair systems creates a

  17. Understanding Rheumatoid Arthritis (RA): Treatment and Causes

    Science.gov (United States)

    ... this page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Treatment and Causes Past Issues / Summer 2014 Table of Contents How Is Rheumatoid Arthritis Treated? Doctors have many ways to treat this ...

  18. Radiographic changes and factors associated with subsequent progression of damage in weight-bearing joints of patients with rheumatoid arthritis under TNF-blocking therapies-three-year observational study.

    Science.gov (United States)

    Matsushita, Isao; Motomura, Hiraku; Seki, Eiko; Kimura, Tomoatsu

    2017-07-01

    The long-term effects of tumor necrosis factor (TNF)-blocking therapies on weight-bearing joints in patients with rheumatoid arthritis (RA) have not been fully characterized. The purpose of this study was to assess the radiographic changes of weight-bearing joints in patients with RA during 3-year of TNF-blocking therapies and to identify factors related to the progression of joint damage. Changes in clinical variables and radiological findings in 243 weight-bearing joints (63 hips, 54 knees, 71 ankles, and 55 subtalar joints) in 38 consecutive patients were investigated during three years of treatment with TNF-blocking agents. Multivariate logistic regression analysis was used to identify risk factors for the progression of weight-bearing joint damage. Seventeen (14.5%) of proximal weight-bearing joints (hips and knees) showed apparent radiographic progression during three years of treatment, whereas none of the proximal weight-bearing joints showed radiographic evidence of improvement or repair. In contrast, distal weight-bearing joints (ankle and subtalar joints) displayed radiographic progression and improvement in 20 (15.9%) and 8 (6.3%) joints, respectively. Multivariate logistic analysis for proximal weight-bearing joints identified the baseline Larsen grade (p bearing joints identified disease activity at one year after treatment (p bearing joints. Disease activity after treatment was an independent factor for progression of damage in proximal and distal weight-bearing joints. Early treatment with TNF-blocking agents and tight control of disease activity are necessary to prevent the progression of damage of the weight-bearing joints.

  19. Myelin basic protein as a novel genetic risk factor in rheumatoid arthritis--a genome-wide study combined with immunological analyses.

    Directory of Open Access Journals (Sweden)

    Chikashi Terao

    Full Text Available Rheumatoid arthritis (RA is a major cause of adult chronic inflammatory arthritis and a typical complex trait. Although several genetic determinants have been identified, they account for only a part of the genetic susceptibility. We conducted a genome-wide association study of RA in Japanese using 225,079 SNPs genotyped in 990 cases and 1,236 controls from two independent collections (658 cases and 934 controls in collection1; 332 cases and 302 controls in collection2, followed by replication studies in two additional collections (874 cases and 855 controls in collection3; 1,264 cases and 948 controls in collection4. SNPs showing p<0.005 in the first two collections and p<10(-4 by meta-analysis were further genotyped in the latter two collections. A novel risk variant, rs2000811, in intron2 of the myelin basic protein (MBP at chromosome 18q23 showed strong association with RA (p = 2.7×10(-8, OR 1.23, 95% CI: 1.14-1.32. The transcription of MBP was significantly elevated with the risk allele compared to the alternative allele (p<0.001. We also established by immunohistochemistry that MBP was expressed in the synovial lining layer of RA patients, the main target of inflammation in the disease. Circulating autoantibody against MBP derived from human brain was quantified by ELISA between patients with RA, other connective tissue diseases and healthy controls. As a result, the titer of anti-MBP antibody was markedly higher in plasma of RA patients compared to healthy controls (p<0.001 and patients with other connective tissue disorders (p<0.001. ELISA experiment using citrullinated recombinant MBP revealed that a large fraction of anti-MBP antibody in RA patients recognized citrullinated MBP. This is the first report of a genetic study in RA implicating MBP as a potential autoantigen and its involvement in pathogenesis of the disease.

  20. Case report patients diagnosed with rheumatoid arthritis

    OpenAIRE

    Váňová, Tereza

    2012-01-01

    Title of bachelors thesis: Case report patients diagnosed with rheumatoid arthritis Summary: The work is focused on diseases rheumatoid arthritis and its physiotherapy care. It consists of two parts. Part of the general anatomy of the joint contains a general, deals with the disease rheumatoid arthritis, its diagnosis, treatment and comprehensive rehabilitation treatment. Part has its own special case report physiotherapy sessions on this topic. Key words: rheumatoid arthritis, comprehensive ...

  1. "I could cry, the amount of shoes I can't get into": A qualitative exploration of the factors that influence retail footwear selection in women with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Naidoo Serena

    2011-07-01

    Full Text Available Abstract Background Studies have reported that women with rheumatoid arthritis (RA are not wearing NHS supplied therapeutic footwear; therefore it is likely they are wearing footwear sourced through retailers. Previous research gives limited information (largely associated with cosmesis on people's perceptions on the relationships that exist between retail footwear, well-being and quality of life. This study aimed to explore the perceptions of women with RA regarding their choice of retail footwear and identify the factors influencing retail footwear selection. Methods Eleven women with RA wearing normal retail footwear were recruited from an out-patient podiatry clinic in the south east of England. Semi-structured interviews were carried out and an interpretative phenomenological approach was adopted for data collection and transcript analysis. Results Six key themes were revealed from the analysis: (1 the nature of foot complaints and deformities, (2 aesthetic appearance and design of footwear, (3 body image, (4 psychosocial aspects, (5 Perceptions of footwear and (6 the therapeutic value of retail shoes. These contributed to an overarching concept of loss of choice associated with retail footwear. In particular, the areas discussed most frequently throughout were themes (2, (3 and (4, which were notably more 'emotional' in nature. Conclusions Limitations in retail footwear for these women have impacted on their individuality, linking significantly with their body image. The loss of choice in footwear as a consequence of the disease impacts negatively on emotions, wellbeing and was identified in reduced self-perceived quality of life.

  2. The association between insulin-like growth factor 1 (IGF-1), IGF-binding proteins (IGFBPs), and the carboxyterminal propeptide of type I procollagen (PICP) in pre- and postmenopausal women with rheumatoid arthritis.

    Science.gov (United States)

    Szeremeta, A; Jura-Półtorak, A; Komosińska-Vassev, K; Zoń-Giebel, A; Kapołka, D; Olczyk, K

    2017-05-01

    To assess the association between plasma levels of the insulin-like growth factor (IGF) system including IGF-1, IGF-binding proteins (IGFBPs) including IGFBP-1, total (t-)IGFBP-3 and functional (f-)IGFBP-3, and the carboxyterminal propeptide of type I procollagen (PICP) in pre- and postmenopausal women with rheumatoid arthritis (RA). Plasma concentrations of IGF-1, IGFBP-1, t-IGFBP-3, f-IGFBP-3, and PICP were measured by immunoassay. No significant difference was observed in plasma IGF-1 levels between pre- and postmenopausal subjects. Plasma levels of IGFBP-1 were elevated in RA. PICP and f-IGFBP-3 were greatly affected by menopausal status. Of the three IGFBPs tested, only f-IGFBP-3 plasma levels in RA women correlated negatively with age and disease duration. A positive correlation was demonstrated between PICP and erythrocyte sedimentation rate (ESR) in RA. Moreover, there was no correlation between PICP and IGF-1 and any of the IGFBPs in RA women. Considerable disruption of the IGF system in RA was found to be related to disease activity and duration. Changes in the IGF-IGFBP axis and PICP levels were different in pre- and postmenopausal women with RA. Elevated plasma PICP concentrations may indicate an increased rate of bone formation in postmenopausal RA women. Additionally, the observed changes in the IGF/IGFBP system did not affect bone formation during RA.

  3. "I could cry, the amount of shoes I can't get into": A qualitative exploration of the factors that influence retail footwear selection in women with rheumatoid arthritis

    Science.gov (United States)

    2011-01-01

    Background Studies have reported that women with rheumatoid arthritis (RA) are not wearing NHS supplied therapeutic footwear; therefore it is likely they are wearing footwear sourced through retailers. Previous research gives limited information (largely associated with cosmesis) on people's perceptions on the relationships that exist between retail footwear, well-being and quality of life. This study aimed to explore the perceptions of women with RA regarding their choice of retail footwear and identify the factors influencing retail footwear selection. Methods Eleven women with RA wearing normal retail footwear were recruited from an out-patient podiatry clinic in the south east of England. Semi-structured interviews were carried out and an interpretative phenomenological approach was adopted for data collection and transcript analysis. Results Six key themes were revealed from the analysis: (1) the nature of foot complaints and deformities, (2) aesthetic appearance and design of footwear, (3) body image, (4) psychosocial aspects, (5) Perceptions of footwear and (6) the therapeutic value of retail shoes. These contributed to an overarching concept of loss of choice associated with retail footwear. In particular, the areas discussed most frequently throughout were themes (2), (3) and (4), which were notably more 'emotional' in nature. Conclusions Limitations in retail footwear for these women have impacted on their individuality, linking significantly with their body image. The loss of choice in footwear as a consequence of the disease impacts negatively on emotions, wellbeing and was identified in reduced self-perceived quality of life. PMID:21794134

  4. Production of Monoclonal Antibodies specific for Progesterone

    OpenAIRE

    YÜCEL, Fatıma

    2014-01-01

    Progesterone levels in milk and serum are indicators of pregnancy in cattle. The progesterone level reaches a peak on the 21 st and 22 nd days of pregnancy. Monoclonal antibodies specific to progesterone could be used for the immunodetection of milk and serum progesterone levels. We report here the development of hybrid cells prdoducing monoclonal antibodies specific for progesterone using hybridoma technology. Hybridoma cells secreting monoclonal antibodies against progesterone (MAM 2H1...

  5. Crescentic glomerular nephritis associated with rheumatoid arthritis: a case report.

    Science.gov (United States)

    Balendran, K; Senarathne, L D S U; Lanerolle, R D

    2017-07-21

    Rheumatoid arthritis is a systemic disorder where clinically significant renal involvement is relatively common. However, crescentic glomerular nephritis is a rarely described entity among the rheumatoid nephropathies. We report a case of a patient with rheumatoid arthritis presenting with antineutrophil cytoplasmic antibody-negative crescentic glomerular nephritis. A 54-year-old Sri Lankan woman who had recently been diagnosed with rheumatoid arthritis was being treated with methotrexate 10 mg weekly and infrequent nonsteroidal anti-inflammatory drugs. She presented to our hospital with worsening generalized body swelling and oliguria of 1 month's duration. Her physical examination revealed that she had bilateral pitting leg edema and periorbital edema. She was not pale or icteric. She had evidence of mild synovitis of the small joints of the hand bilaterally with no deformities. No evidence of systemic vasculitis was seen. Her blood pressure was 170/100 mmHg, and her jugular venous pressure was elevated to 7 cm with an undisplaced cardiac apex. Her urine full report revealed 2+ proteinuria with active sediment (dysmorphic red blood cells [17%] and granular casts). Her 24-hour urinary protein excretion was 2 g. Her serum creatinine level was 388 μmol/L. Abdominal ultrasound revealed normal-sized kidneys with acute parenchymal changes and mild ascites. Her renal biopsy showed renal parenchyma containing 20 glomeruli showing diffuse proliferative glomerular nephritis, with 14 of 20 glomeruli showing cellular crescents, and the result of Congo red staining was negative. Her rheumatoid factor was positive with a high titer (120 IU/ml), but results for antinuclear antibody, double-stranded deoxyribonucleic acid, and antineutrophil cytoplasmic antibody (perinuclear and cytoplasmic) were negative. Antistreptolysin O titer rheumatoid arthritis, awareness of which would facilitate early appropriate investigations and treatment.

  6. Prognostic Factors Toward Clinically Relevant Radiographic Progression in Patients With Rheumatoid Arthritis in Clinical Practice: A Japanese Multicenter, Prospective Longitudinal Cohort Study for Achieving a Treat-to-Target Strategy.

    Science.gov (United States)

    Koga, Tomohiro; Okada, Akitomo; Fukuda, Takaaki; Hidaka, Toshihiko; Ishii, Tomonori; Ueki, Yukitaka; Kodera, Takao; Nakashima, Munetoshi; Takahashi, Yuichi; Honda, Seiyo; Horai, Yoshiro; Watanabe, Ryu; Okuno, Hiroshi; Aramaki, Toshiyuki; Izumiyama, Tomomasa; Takai, Osamu; Miyashita, Taiichiro; Sato, Shuntaro; Kawashiri, Shin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Origuchi, Tomoki; Nakamura, Hideki; Aoyagi, Kiyoshi; Eguchi, Katsumi; Kawakami, Atsushi

    2016-04-01

    To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) in clinical practice.We performed a multicenter prospective study in Japan of biological disease-modifying antirheumatic drug (bDMARD)-naive RA patients with moderate to high disease activity treated with conventional synthetic DMARDs (csDMARDs) at study entry. We longitudinally observed 408 patients for 1 year and assessed disease activity every 3 months. CRRP was defined as yearly progression of modified total Sharp score (mTSS) > 3.0 U. We also divided the cohort into 2 groups based on disease duration (<3 vs ≥3 years) and performed a subgroup analysis.CRRP was found in 10.3% of the patients. A multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: CRP at baseline (0.30 mg/dL increase, 95% confidence interval [CI] 1.01-1.11), time-integrated Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) during the 1 year postbaseline (12.4-unit increase, 95%CI 1.17-2.59), RA typical erosion at baseline (95%CI 1.56-21.1), and the introduction of bDMARDs (95%CI 0.06-0.38). The subgroup analysis revealed that time-integrated DAS28-ESR is not a predictor whereas the introduction of bDMARDs is a significant protective factor for CRRP in RA patients with disease duration <3 years.We identified factors that could be used to predict the development of CRRP in RA patients treated with DMARDs. These variables appear to be different based on the RA patients' disease durations.

  7. SPECT assay of radiolabeled monoclonal antibodies

    International Nuclear Information System (INIS)

    Jaszczak, R.J.

    1992-02-01

    The long-term goal of this research project is to develop methods to improve the utility of single photon emission computed tomography (SPECI) to quantify the biodistribution of monoclonal antibodies (MoAbs) labeled with clinically relevant radionuclides ( 123 I, 131 I, and 111 In) and with another radionuclide, 211 At, recently used in therapy. We describe here our progress in developing quantitative SPECT methodology for 111 In and 123 I. We have focused our recent research thrusts on the following aspects of SPECT: (1) The development of improved SPECT hardware, such as improved acquisition geometries. (2) The development of better reconstruction methods that provide accurate compensation for the physical factors that affect SPECT quantification. (3) The application of carefully designed simulations and experiments to validate our hardware and software approaches

  8. Monoclonal antibodies for treating cancer

    International Nuclear Information System (INIS)

    Dillman, R.O.

    1989-01-01

    The purpose of this study is to assess the current status of in-vivo use of monoclonal antibodies for treating cancer. Publications appearing between 1980 and 1988 were identified by computer searches using MEDLINE and CANCERLIT, by reviewing the table of contents of recently published journals, and by searching bibliographies of identified books and articles. More than 700 articles, including peer-reviewed articles and book chapters, were identified and selected for analysis. The literature was reviewed and 235 articles were selected as relevant and representative of the current issues and future applications for in-vivo monoclonal antibodies for cancer therapy and of the toxicity and efficacy which has been associated with clinical trials. Approaches include using antibody alone (interacting with complement or effector cells or binding directly with certain cell receptors) and immunoconjugates (antibody coupled to radioisotopes, drugs, toxins, or other biologicals). Most experience has been with murine antibodies. Trials of antibody alone and radiolabeled antibodies have confirmed the feasibility of this approach and the in-vivo trafficking of antibodies to tumor cells. However, tumor cell heterogeneity, lack of cytotoxicity, and the development of human antimouse antibodies have limited clinical efficacy. Although the immunoconjugates are very promising, heterogeneity and the antimouse immune response have hampered this approach as has the additional challenge of chemically or genetically coupling antibody to cytotoxic agents. As a therapeutic modality, monoclonal antibodies are still promising but their general use will be delayed for several years. New approaches using human antibodies and reducing the human antiglobulin response should facilitate treatment. 235 references

  9. RHEUMATOID ARTHRITIS AND PREGNANCY

    Directory of Open Access Journals (Sweden)

    N. M. Kosheleva

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA generally starts at the age when many women have already become mothers; however, it may occur in childhood or adolescence. Furthermore, there has been recently a women’s tendency to plan pregnacy for a more mature age, which necessitates a discussion about gestation in this disease. Investigation of mechanisms pregnancy can influence the development of RA both in the gestation and long-term periods is of important theoretical and practical value. The results of these investigations may be used to develop new treatments for RA and management tactics for patients during pregnancy and lactation. The  aper gives the data available in the literature on fertility in RA, impact of pregnancy on its activity and that of RA on the course and outcomes of gestation, as well as current ideas on lactation and use of oral contraceptives in RA. Particular attention is given to drug therapy in pregnant and breastfeeding women with RA: groups of anti-rheumatic drugs are considered in detail in relation to the safety of or a potential risk from their use. A therapeutic algorithm and recommendations for pregnancy planning and a follow-up of patients with RA during gestation are proposed.

  10. Monoclonal antibody-based immunoassays.

    Science.gov (United States)

    Appleby, P; Reischl, U

    1998-01-01

    An immunoassay may be defined as an assay that employs an immunological reagent, usually an antibody, to confer specificity for the ligand being measured. As a corollary to this, the discovery, and subsequent development, of monoclonal antibodies (MAbs) has greatly expanded the application and use of immunoassays. Polyclonal reagents, with their associated problems of specificity and quality control, have now been largely replaced by readily available MAbs of potential immortality and well-defined specificity and affinity. This has resulted, in the last two decades, in a great expansion in the range of immunoassays available and also a significant improvement in their reproducibility and reliability.

  11. Mapping of monoclonal antibody- and receptor-binding domains on human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) using a surface plasmon resonance-based biosensor.

    Science.gov (United States)

    Laricchia-Robbio, L; Liedberg, B; Platou-Vikinge, T; Rovero, P; Beffy, P; Revoltella, R P

    1996-10-01

    An automated surface plasmon resonance (SPR)-based biosensor system has been used for mapping antibody and receptor-binding regions on the recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) molecule. A rabbit antimouse IgG1-Fc antibody (RAM.Fc) was coupled to an extended carboxymethylated-hydrogel matrix attached to a gold surface in order to capture an anti-rhGM-CSF monoclonal antibody (MAb) injected over the sensing layer. rhGM-CSF was subsequently injected and allowed to bind to this antibody. Multisite binding assays were then performed, by flowing sequentially other antibodies and peptides over the surface, and the capacity of the latter to interact with the entrapped rhGM-CSF in a multimolecular complex was monitored in real time with SPR. Eleven MAb (all IgG1K), were analyzed: respectively, four antipeptide MAb raised against three distinct epitopes of the cytokine (two clones against residues 14-24, that includes part of the first alpha-helix toward the N-terminal region; one clone against peptide 30-41, an intrahelical loop; and one clone against residues 79-91, including part of the third alpha-helix) and seven antiprotein MAbs raised against the entire rhGM-CSF, whose target native epitopes are still undetermined. In addition, the binding capacity to rhGM-CSF of a synthetic peptide, corresponding to residues 238-254 of the extracellular human GM-CSF receptor alpha-chain, endowed with rhGM-CSF binding activity, was tested. The results from experiments performed with the biosensor were compared with those obtained by a sandwich enzyme-linked immunosorbent assay (ELISA), using the same reagents. The features of the biosensor technology (fully automated, measure in real time, sharpened yes/no response, less background disturbances, no need for washing step or labeling of the reagent) offered several advantages in these studies of MAb immunoreactivity and epitope mapping, giving a much better resolution and enabling more distinct

  12. Ultrasound-detected bone erosion is a relapse risk factor after discontinuation of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis whose ultrasound power Doppler synovitis activity and clinical disease activity are well controlled.

    Science.gov (United States)

    Kawashiri, Shin-Ya; Fujikawa, Keita; Nishino, Ayako; Okada, Akitomo; Aramaki, Toshiyuki; Shimizu, Toshimasa; Umeda, Masataka; Fukui, Shoichi; Suzuki, Takahisa; Koga, Tomohiro; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Mizokami, Akinari; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Aoyagi, Kiyoshi; Maeda, Takahiro; Kawakami, Atsushi

    2017-05-25

    In the present study, we explored the risk factors for relapse after discontinuation of biologic disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) whose ultrasound power Doppler (PD) synovitis activity and clinical disease activity were well controlled. In this observational study in clinical practice, the inclusion criteria were based on ultrasound disease activity and clinical disease activity, set as low or remission (Disease Activity Score in 28 joints based on erythrocyte sedimentation rate Ultrasound was performed in 22 joints of bilateral hands at discontinuation for evaluating synovitis severity and presence of bone erosion. Patients with a maximum PD score ≤1 in each joint were enrolled. Forty patients with RA were consecutively recruited (November 2010-March 2015) and discontinued bDMARD therapy. Variables at the initiation and discontinuation of bDMARD therapy that were predictive of relapse during the 12 months after discontinuation were assessed. The median patient age was 54.5 years, and the median disease duration was 3.5 years. Nineteen (47.5%) patients relapsed during the 12 months after the discontinuation of bDMARD therapy. Logistic regression analysis revealed that only the presence of bone erosion detected by ultrasound at discontinuation was predictive of relapse (OR 8.35, 95% CI 1.78-53.2, p = 0.006). No clinical characteristics or serologic biomarkers were significantly different between the relapse and nonrelapse patients. The ultrasound synovitis scores did not differ significantly between the groups. Our findings are the first evidence that ultrasound bone erosion may be a relapse risk factor after the discontinuation of bDMARD therapy in patients with RA whose PD synovitis activity and clinical disease activity are well controlled.

  13. A rheumatoid nodule mimicking soft tissue sarcoma on MR: a case report

    International Nuclear Information System (INIS)

    Choi, Joon Il; Kong, Keun Young; Kang, Heung Sik

    2000-01-01

    We report a case of rheumatoid nodule of the right knee in a 55-year-old woman which on the basis of MR images was misdiagnosed as soft tissue sarcoma. Reumatoid nodules occur in up to 20% of adult patients with rheumatoid arthritis and most patients with rheumatoid nodules are rheumatoid factor positive. The nodules are most commonly located between the skin and an underlying bony prominence. In this case, the patient had a history of rheumatoid arthritis and a soft tissue mass was present in the lateral aspect of the right knee. T1-weighted images revealed a mass of similar signal intensity to that of muscle, and on T2-weighted images, a central portion of high signal intensity was noted. Enhanced T1-weighted images demonstrated peripheral rim enhancement. The mass extended to subcutaneous tissue, with penetration of lateral patellar retinaculum. Excisional biopsy was performed, and the pathologic diagnosis was rheumatoid nodule. Although its radiologic findings are non-specific, rheumatoid nodule should -in appropriate clinical setting- be included in the differential diagnosis of a predominantly solid or centrally necrotic periarticular soft tissue. (author)

  14. Dietetic recommendations in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    María Rosa Alhambra-Expósito

    2013-12-01

    Full Text Available Rheumatoid arthritis (RA is a chronic autoimmune disease that has a significant effect on patients’ physical, emotional, and social functioning. For decades, patients have used different diets to try to improve the symptoms of RA. The possible benefits of dietary therapy for rheumatoid arthritis are reviewed in this article. Nutritional objectives for RA, are to halt the loss of bone mass, promote healing of bone fractures and improving bone-associated inflammatory disorders and joints. In general, diets low in saturated fat, rich in polyunsaturated fats: omega 3 and omega 6, rich in complex carbohydrates and fiber are recommended.

  15. Radiological aspects of rheumatoid arthritis

    International Nuclear Information System (INIS)

    Schacherl, M.

    1985-01-01

    An introductory summary of the imaging-diagnosis will be given. The necessity of acquiring a catalogue of application to particular imaging methods is emphasized. Discussion of step by step diagnosis regarding rheumatologic questions is given on example of the hand. Technically insufficient radiographs and bad habits during diagnostic analysis are pointed out. Radiologic problems in differentiating arthritis/osteoarthrosis will be mentioned. The discussion of these points is followed by outlining the radiology of rheumatoid arthritis and the complexity of this disease. Introduction of a new stage classification. Finally twelve basic radiologic types of rheumatoid arthritis will be presented. (orig.) [de

  16. Monoclonal antibody hapten radiopharmaceutical delivery

    International Nuclear Information System (INIS)

    Goodwin, D.A.; McTigue, M.

    1986-01-01

    One hundred μg of monoclonal antibody (MoAb) CHA255 with a binding constant Kb of 4 x 10 9 was complexed with indium-111 labelled BLEDTA II, BLEDTA IV, benzyl EDTA, and an EDTA conjugate of Fab. The 24-h tumour and organ distribution of BALB/c mice bearing KHJJ tumours was studied for each compound alone, the antibody complex, and 3 h following a chelate chase of the antibody complex. Whole body biological half-life was measured for 7 days with and without a chelate chase for each antibody complex. The 24-h whole body counts dropped 20 to 60% and blood concentration fell over 89% within 3 h of administering the chelate chase. Theoretical equivalent human organ doses were calculated from the 24-h organ concentrations, effective half-life, and MIRD 11 S values (absorbed dose per cumulated activity). Liver and spleen were the target organs, with the dose ranging from 0.50 to 3.91 rads mCi -1 . The reduction in organ radiation dose varied up to 95% following the chelate chase. Rapid selective renal clearance of chelate labelled radiopharmaceuticals by competitive inhibition (chelate chase) of their reversible binding to monoclonal antibodies enhances tumour imaging and improves the radiation dosimetry. (author)

  17. Uses of monoclonal antibody 8H9

    Energy Technology Data Exchange (ETDEWEB)

    Cheung, Nai-Kong V.

    2018-04-10

    This invention provides a composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a suitable carrier. This invention provides a pharmaceutical composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a pharmaceutically acceptable carrier. This invention also provides an antibody other than the monoclonal antibody 8H9 comprising the complementary determining regions of monoclonal antibody 8H9 or a derivative thereof, capable of binding to the same antigen as the monoclonal antibody 8H9. This invention provides a substance capable of competitively inhibiting the binding of monoclonal antibody 8H9. This invention also provides an isolated scFv of monoclonal antibody 8H9 or a derivative thereof. This invention also provides the 8H9 antigen. This invention also provides a method of inhibiting the growth of tumor cells comprising contacting said tumor cells with an appropriate amount of monoclonal antibody 8H9 or a derivative thereof.

  18. SECONDARY OSTEOARTHRITIS IN RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    I. A. Starodubtseva

    2015-01-01

    Full Text Available The paper considers the problems of comorbidities in patients with rheumatoid arthritis (RA. Two or more RA-related conditions were diagnosed according to the results of the QUEST-RA program implemented in 34 countries. Osteoarthritis along with hypertension, hyperlipidemia, and osteoporosis was detected among the most commonly diseases. Owing to expanded diagnostic capabilities, the recognition and treatment of the comorbidities have recently received much attention, as embodied in the draft Association of Rheumatologists of Russia Guidelines for RA management (2014; Part 1. The concept and major characteristics of secondary osteoarthritis in RA are analyzed. It is precisely the inflammatory process and underlying disease-related risk factors, including treatment, that have impact on the development of secondary osteoarthritis and patients’ quality of life as a whole. All this allows an inference about the mechanisms closely intertwined with the underlying disease for the development of secondary osteoarthritis, which initiates cartilage damage and further remodeling. Primary and secondary osteoarthritis was comparatively analyzed. Particular emphasis is placed on current cartilage biomarkers, their diagnostic value and role in monitoring the efficiency of treatment in clinical trials. The paper provides a comparative analysis of detectable serum and urine biomarkers according to the results of the complex analysis made by the National Institutes of Health. Particular attention is given to cartilage oligomeric matrix protein (COMP. Foreign authors’ investigations suggest that there is a relationship between serum COMP levels and disease severity and joint X-ray changes. There is evidence for the efficacy of hyaluronic acid used in the treatment of secondary osteoarthritis in patients with RA. 

  19. Decrease in sick leave among patients with rheumatoid arthritis in the first 12 months after start of treatment with tumour necrosis factor antagonists: a population-based controlled cohort study.

    Science.gov (United States)

    Olofsson, Tor; Englund, Martin; Saxne, Tore; Jöud, Anna; Jacobsson, Lennart T H; Geborek, Pierre; Allaire, Saralynn; Petersson, Ingemar F

    2010-12-01

    To investigate the effect of tumour necrosis factor (TNF) antagonist treatment of patients with rheumatoid arthritis (RA) on sick leave (SL) and disability pension (DP) in a population-based setting in southern Sweden. All patients with RA in the South Swedish Arthritis Treatment Group register living in the county of Skåne (population 1.2 million), who started their first treatment with a TNF antagonist between January 2004 and December 2007 and were 18-58 years at treatment start (n = 365), were identified. For each patient with RA, four matched reference subjects from the general population were randomly selected. Data were linked to the Swedish Social Insurance Agency register and the point prevalence of SL and DP as well as days of SL and DP per month were calculated from 360 days before until 360 days after treatment start. At treatment start 38.6% of the patients with RA were registered for SL. During the first 6 months this share dropped to 28.5% (decrease by 26.2%, ptreatment year. Comparing patients with RA to the reference group the relative risk of being on SL was 6.6 (95% CI 5.2 to 8.5) at initiation of anti-TNF treatment and 5.2 (95% CI 4.0 to 6.8) 1 year after that. The corresponding figures for DP were 3.4 (95% CI 2.7 to 4.2) and 3.2 (95% CI 2.7 to 3.9). There was a marked decline in SL during the first 6 months of TNF antagonist treatment in patients with RA in southern Sweden, maintained throughout the first year, which was not offset by a corresponding increase in DP.

  20. Tocilizumab in patients with active rheumatoid arthritis and inadequate response to disease-modifying antirheumatic drugs or tumor necrosis factor inhibitors: subanalysis of Spanish results of an open-label study close to clinical practice.

    Science.gov (United States)

    Álvaro-Gracia, José M; Fernández-Nebro, Antonio; García-López, Alicia; Guzmán, Manuel; Blanco, Francisco J; Navarro, Francisco J; Bustabad, Sagrario; Armendáriz, Yolanda; Román-Ivorra, José A

    2014-01-01

    To analyze the Spanish experience in an international study which evaluated tocilizumab in patients with rheumatoid arthritis (RA) and an inadequate response to conventional disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor inhibitors (TNFis) in a clinical practice setting. Subanalysis of 170 patients with RA from Spain who participated in a phase IIIb, open-label, international clinical trial. Patients presented inadequate response to DMARDs or TNFis. They received 8mg/kg of tocilizumab every 4 weeks in combination with a DMARD or as monotherapy during 20 weeks. Safety and efficacy of tocilizumab were analyzed. Special emphasis was placed on differences between failure to a DMARD or to a TNFi and the need to switch to tocilizumab with or without a washout period in patients who had previously received TNFi. The most common adverse events were infections (25%), increased total cholesterol (38%) and transaminases (15%). Five patients discontinued the study due to an adverse event. After six months of tocilizumab treatment, 71/50/30% of patients had ACR 20/50/70 responses, respectively. A higher proportion of TNFi-naive patients presented an ACR20 response: 76% compared to 64% in the TNFi group with previous washout and 66% in the TNFi group without previous washout. Safety results were consistent with previous results in patients with RA and an inadequate response to DMARDs or TNFis. Tocilizumab is more effective in patients who did not respond to conventional DMARDs than in patients who did not respond to TNFis. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  1. Comparative efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with active rheumatoid arthritis that inadequately responds to tumor necrosis factor inhibitors: a Bayesian network meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Lee, Young Ho; Bae, Sang-Cheol

    2016-11-01

    This study aimed to assess the relative efficacy and safety of biologics and tofacitinib in patients with rheumatoid arthritis (RA) showing an inadequate response to tumor necrosis factor (TNF) inhibitors. We performed a Bayesian network meta-analysis to combine the direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with RA that inadequately responds to TNF inhibitors. Four RCTs including 1796 patients met the inclusion criteria. The tocilizumab 8 mg group showed a significantly higher American College of Rheumatology 20% (ACR20) response rate than the abatacept and tofacitinib groups. Ranking probability based on surface under the cumulative ranking curve (SUCRA) indicated that tocilizumab 8 mg had the highest probability of being the best treatment for achieving the ACR20 response rate (SUCRA = 0.9863), followed by rituximab (SUCRA = 0.6623), abatacept (SUCRA = 0.5428), tocilizumab 4 mg (SUCRA = 0.4956), tofacitinib 10 mg (SUCRA = 0.4715), tofacitinib 5 mg (SUCRA = 0.3415) and placebo (SUCRA = 0). In contrast, the safety based on the number of withdrawals due to adverse events did not differ significantly among the treatment options. Tocilizumab 8 mg was the second-line non-TNF biologic with the highest performance regarding an early good response based on ACR20 response rate and acceptable safety profile, followed by rituximab, abatacept and tofacitinib in patients with RA and an inadequate response to anti-TNF therapy, and none of these treatments were associated with a significant risk of withdrawal due to adverse events. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  2. Interstitial lung involvement in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    David Vladimirovich Bestaev

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA is a systemic autoimmune rheumatic disease of unknown etiology, characterized by chronic erosive arthritis and extraarticular manifestations. Pulmonary involvement is one of the common extraarticular manifestations of RA and may show itself as bronchial tree lesions, rheumatoid nodules, Caplan's syndrome, and lesions in the pleura or pulmonary interstitium (interstitial lung involvement (ILI. High-resolution computed tomography allows the diagnosis of ILI in RA in nearly 70% of cases although the incidence of ILI may be lower (4 to 30% depending on diagnostic methods and patient selection criteria. There are several histopathological types of ILI, the differential diagnosis of which can be troublesome. Usual interstitial pneumonia (UIP and nonspecific interstitial pneumonia are major types of RA-associated ILI. UIP-pattern ILI has a more severe course than ILI with other histological patterns. The clinical presentation of ILI may be complicated by the likely toxic effect of a number of disease-modifying antirheumatic drugs (DMARDs used to treat RA, such as methotrexate and leflunomide, and biological agents (BAs, tumor necrosis factor-α (TNF-α inhibitors. The pathogenesis of pulmonary involvement in RA and the role of synthetic DMARDs and BAs in the development of ILI call for further investigations.An extraarticular manifestation, such as ILI, affects the choice of treatment policy in patients with RA.The relevance of a study of ILI is beyond question. The paper discusses the state-of-the-art of investigations in this area.

  3. Coexistence of bronchiectasis and rheumatoid arthritis: revisited.

    Science.gov (United States)

    Wilczynska, Maria M; Condliffe, Alison M; McKeon, Damian J

    2013-04-01

    The presence of bronchiectasis (BR) in patients with rheumatoid arthritis (RA) has been recognized for many decades; nevertheless, little research has been undertaken in this area. It is important to recognize that BR coexistent with RA differs from the other types of BR. The purpose of this descriptive review was to delineate the epidemiology, etiology, risk factors, pulmonary function testing, imaging, prognosis and management of concomitant BR and RA. To inform our study we searched the PubMed, EMBASE, CINAHL, and MEDLINE databases, using combinations of the following key words: computed tomography, lung function tests, rheumatoid arthritis, bronchiectasis, biological agents, and interstitial lung disease. The number of published papers covering this topic is limited, but several relevant conclusions can be drawn. Patients with concomitant RA and BR have worse obstructive airways disease, increased susceptibility to recurrent pulmonary infections, faster lung function decline, and higher mortality, compared with subjects with either RA or BR alone. The use of disease-modifying anti-rheumatic drugs (both biological and non-biological) for RA in RA-BR patients imparts a further challenge in managing these patients. Although there are not any published guidelines on the management of coexisting RA-BR, we have attempted to provide such recommendations, based on the literature review and our experience.

  4. Course and prognosis in seropositive and seronegative rheumatoid arthritis.

    Science.gov (United States)

    Sahatçiu-Meka, Vjollca; Rexhepi, Sylejman; Kukeli, Anton; Manxhuka-Kërliu, Suzana; Pallaskas, Kelmend; Murtezani, Ardiana; Rexhepi, Mjellma; Rexhepi, Blerta

    2013-01-01

    Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis (RA), diagnosed with negative rheumatoid factor (RF) tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis. The aim of the study was to establish a scientific comparative analysis between RA seronegative and seropositive, regarding course and prognoses of the disease. Two hundred fifty patients with rheumatoid arthritis according to the (American College of Rheumatology) criteria were retrospectively studied by analysis the course and prognoses of disease. All examinees were between 25-60 years of age (Xb=49.9, SD=10.3) with disease duration between 1-27 years (Xbox=6.41, SD=6.47). Course of the disease with "remissions and exacerbations", progressive continual course and bad prognoses, were more presented in seropositive group ofpatients. Partial remission was more common in seronegative patients but according to serostatus and gender has not shown statistically significant difference. Duration of the disease was a specific prognostic sign for both subsets [(r=0.32, p0.05) seronegative, (r=0.18, p<0.05) seropositive]. Seropositive and seronegative RA distinguish in course and prognostic feature, but not enough to differentiate them in two different forms of the disease. Regarding the sero-status, differences within sex, with some exceptions, are not relevant.

  5. Extra-Articular Manifestations of Rheumatoid Arthritis, Now

    Directory of Open Access Journals (Sweden)

    Paloma Vela

    2014-06-01

    Full Text Available Rheumatoid arthritis (RA is a chronic systemic inflammatory disease, characterised by polyarthritis and extra-articular organ disease, including rheumatoid nodules, ophthalmologic manifestations, cardiopulmonary disease, vasculitis, neuropathy, glomerulonephritis, Felty’s syndrome, and amyloidosis. Extra-articular manifestations of RA (ExRA occur in 17.8–40.9% of RA patients, 1.5–21.5% of them presenting as severe forms and usually associated with increased morbidity and mortality. They can develop at any time during the course of the disease, even in the early stages, and are associated with certain predisposing factors, such as the presence of rheumatoid factor, smoking, and long-standing severe disease. Rheumatoid nodules, the most common ExRA, have been found to be associated with the development of severe features, such as vasculitis, rheumatoid lung disease, pericarditis, and pleuritis, especially in those patients who develop them within 2 years from RA diagnosis. There is no uniformity in the definition of the term ExRA, which limits comparability between different studies. Several recent surveys suggest a lower frequency, probably due to a better control of disease activity. Diagnosis of ExRA is a challenge for clinicians, given its variable and complex presentation, and the lack of specific diagnostic tests; it must be based on clinical recognition and exclusion of other causes of the signs and symptoms. Furthermore, management continues to be difficult with a bad prognosis in many conditions. This article reviews the clinical aspects of major ExRA, focusing on incidence, clinical features, and therapeutic approaches, and how modern immunosuppressive therapy can change the outcome.

  6. Rheumatoid Arthritis Educational Video Series

    Medline Plus

    Full Text Available ... Patients from Johns Hopkins Stategies to Increase your Level of Physical Activity Role of Body Weight in Osteoarthritis Educational Videos for Patients Rheumatoid Arthritis Educational Video Series Psoriatic Arthritis 101 2010 E.S.C.A.P.E. Study Patient Update Transitioning the JRA ...

  7. Radiographic progession of rheumatoid arthritis

    International Nuclear Information System (INIS)

    Siozos, C.D.

    1981-01-01

    The radiographic progression of rheumatoid arthritis can be graded on a 0-IV scala. For this purpose five objective criteria are used: a) destruction, b) osteoporosis, c) narrowing of joint space, d) luxation and e) ankylosis. The grading of the radiographic progression is defined by the extent and the number of the measured alterations. The radiographic progression can be registered yearly. (orig.) [de

  8. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Breedveld, Ferdinand C; Burmester, Gerd R

    2016-01-01

    BACKGROUND: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this t...

  9. Glucocorticoids in early rheumatoid arthritis

    NARCIS (Netherlands)

    Everdingen, Amalia A. van

    2002-01-01

    For 50 years, glucocorticoids (GC) are used for symptomatic treatment of rheumatoid arthritis (RA). In the last decade, results from clinical studies of treatment with GC as additional therapy to long-acting antirheumatic drugs in patients with early RA suggested also disease-modifying properties of

  10. Glucocorticoid Sensitivity in Rheumatoid Arthritis

    NARCIS (Netherlands)

    R.A.M. Quax

    2013-01-01

    textabstractAccumulating observations of women with rheumatoid arthritis (RA) who ‘spontaneously’ experienced less active disease during pregnancy led to the growing belief by Philip Hench that a hormonal substance had to be involved in the improving clinical conditions of pregnant patients with RA.

  11. Arthritis of the hand - Rheumatoid

    Science.gov (United States)

    ... All Topics A-Z Videos Infographics Symptom Picker Anatomy Bones Joints Muscles Nerves Vessels Tendons About Hand Surgery What is a Hand Surgeon? What is a Hand Therapist? Media Find a Hand Surgeon Home Anatomy Rheumatoid Arthritis Email to a friend * required fields ...

  12. Establishment and evaluation of a transgenic mouse model of arthritis induced by overexpressing human tumor necrosis factor alpha

    Directory of Open Access Journals (Sweden)

    Ge Li

    2016-04-01

    Full Text Available Tumor necrosis factor alpha (TNFα plays a key role in the pathogenesis of rheumatoid arthritis (RA. Blockade of TNFα by monoclonal antibody has been widely used for the therapy of RA since the 1990s; however, its mechanism of efficacy, and potential safety concerns of the treatment are still not fully understood. This study sought to establish a transgenic arthritic mouse model by overexpressing human TNFα (hTNFα and to apply this model as a means to evaluate therapeutic consequences of TNFα inhibitors. The transgenic mouse line (TgTC with FVB background was generated by incorporating 3′-modified hTNFα gene sequences. A progressively erosive polyarthritis developed in the TgTC mice, with many characteristics observed in human rheumatoid arthritis, including polyarticular swelling, impairment of movement, synovial hyperplasia, and cartilage and bone erosion. Gene expression analysis demonstrated that hTNFα is not only expressed in hyperplastic synovial membrane, but also in tissues without lesions, including brain, lung and kidney. Treatment of the TgTC mice with anti-hTNFα monoclonal antibodies (mAb significantly decreased the level of hTNFα in the diseased joint and effectively prevented development of arthritis in a dose-dependent response fashion. Our results indicated that the TgTC mice represent a genetic model which can be used to comprehensively investigate the pathogenesis and therapeutics of TNFα-related diseases.

  13. Clinical Translation and Validation of a Predictive Biomarker for Patritumab, an Anti-human Epidermal Growth Factor Receptor 3 (HER3) Monoclonal Antibody, in Patients With Advanced Non-small Cell Lung Cancer.

    Science.gov (United States)

    Mendell, Jeanne; Freeman, Daniel J; Feng, Wenqin; Hettmann, Thore; Schneider, Matthias; Blum, Sabine; Ruhe, Jens; Bange, Johannes; Nakamaru, Kenji; Chen, Shuquan; Tsuchihashi, Zenta; von Pawel, Joachim; Copigneaux, Catherine; Beckman, Robert A

    2015-03-01

    During early clinical development, prospective identification of a predictive biomarker and validation of an assay method may not always be feasible. Dichotomizing a continuous biomarker measure to classify responders also leads to challenges. We present a case study of a prospective-retrospective approach for a continuous biomarker identified after patient enrollment but defined prospectively before the unblinding of data. An analysis of the strengths and weaknesses of this approach and the challenges encountered in its practical application are also provided. HERALD (NCT02134015) was a double-blind, phase 2 study in patients with non-small cell lung cancer (NSCLC) randomized to erlotinib with placebo or with high or low doses of patritumab, a monoclonal antibody targeted against human epidermal growth factor receptor 3 (HER3). While the primary objective was to assess safety and progression-free survival (PFS), a secondary objective was to determine a single predictive biomarker hypothesis to identify subjects most likely to benefit from the addition of patritumab. Although not identified as the primary biomarker in the study protocol, on the basis of preclinical results from 2 independent laboratories, expression levels of the HER3 ligand heregulin (HRG) were prospectively declared the predictive biomarker before data unblinding but after subject enrollment. An assay to measure HRG mRNA was developed and validated. Other biomarkers, such as epidermal growth factor receptor (EGFR) mutation status, were also evaluated in an exploratory fashion. The cutoff value for high vs. low HRG mRNA levels was set at the median delta threshold cycle. A maximum likelihood analysis was performed to evaluate the provisional cutoff. The relationship of HRG values to PFS hazard ratios (HRs) was assessed as a measure of internal validation. Additional NSCLC samples were analyzed to characterize HRG mRNA distribution. The subgroup of patients with high HRG mRNA levels ("HRG

  14. What People with Rheumatoid Arthritis Need to Know about Osteoporosis

    Science.gov (United States)

    ... Need to Know About Osteoporosis What Is Rheumatoid Arthritis? Rheumatoid arthritis is an autoimmune disease, a disorder in ... new habits for healthy bones. The Link Between Rheumatoid Arthritis and Osteoporosis Studies have found an increased risk ...

  15. Factors associated with influenza and pneumococcal vaccine uptake among rheumatoid arthritis patients in Denmark invited to participate in a pneumococcal vaccine trial (Immunovax_RA)

    DEFF Research Database (Denmark)

    Nguyen, MTT; Lindegaard, H.; Hendricks, O.

    2017-01-01

    the survey during scheduled follow-up visits. The questionnaire included questions concerning previous influenza and pneumococcal vaccine uptake, attitudes about vaccination, and socio-demographic factors. Factors associated with recalled vaccine uptake were assessed by multivariate logistic regression....... Results: A total of 192 RA patients completed the survey, 134 (70%) of whom were women and 90 (47%) were aged ≥ 65 years. Sixty-seven patients (35%) received conventional disease-modifying anti-rheumatic drugs (cDMARDs) and 125 (65%) combination therapy with biological disease-modifying anti...

  16. Cardiovascular disease in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Naranjo, Antonio; Sokka, Tuulikki; Descalzo, Miguel

    2008-01-01

    ABSTRACT: INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross...... by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were...... any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0...

  17. Monoclonal antibodies in pediatric allergy

    Directory of Open Access Journals (Sweden)

    Amelia Licari

    2015-10-01

    Full Text Available Production of monoclonal antibodies (mAbs involving human-mouse hybrid cells was first described in 1970s, but these biologics are now used for a variety of diseases including cancers, autoimmune disorders and allergic diseases. The aim of this article is to review current and future applications of mAbs, in particular focusing on anti-IgE therapy, in the field of pediatric allergy. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai, China, Dorret I. Boomsma (Amsterdam, the Netherlands, Gavino Faa (Cagliari, Italy, Antonio Giordano (Philadelphia, USA

  18. The anti-epidermal growth factor receptor (EGFR) monoclonal antibody, C225, enhances radiation-induced apoptosis in primary glioma cell lines through mediation of MAPK/JNK/p38 signaling pathways

    International Nuclear Information System (INIS)

    Chakravarti, A.; Noll, E.; Black, P.M.; Loeffler, J.S.

    2001-01-01

    Purpose: Increasing evidence suggests that signaling mediated by the epidermal growth factor receptor (EGFR) pathway contributes to radiation resistance. The anti-EGFR monoclonal antibody, C225, has been shown to enhance radiation response for several tumor types in preclinical models. Malignant gliomas are known to express, and quite frequently overexpress, EGFR. Our objectives in this study were to 1) Evaluate the efficacy of C225 as a radiation response modifier in EGFR-expressing glioma cell lines and to 2) Investigate the underlying molecular mechanisms mediating C225-induced enhancement of radiation response. Materials and Methods: Twelve EGFR-expressing glioma cells lines, established from patient tumors, were used for this study. Cells were incubated with C225, irradiated, and then evaluated for radiation response. Assays used to evaluate efficacy of C225-mediated radiosensitization included time-course apoptosis assays (Annexin V and TUNEL), viability assays (MTT), and clonogenic survival assays. The changes along MAPK (p44/p42)/JNK/p38-MAPK signal transduction pathways were then investigated using quantitative Western analysis with phospho-specific antibodies to determine the molecular mechanisms by which C225 mediates a given response. Results: C225 clearly enhanced radiation response for 7 of the 12 primary glioma cell lines studied. Enhancement of both immediate and delayed apoptotic responses was evident in these 7 responsive cell lines after C225 administration. The average apoptosis index at 6 hours post-RT+C225 for the 7 responsive lines was 9.5%, compared to 1.2% for the RT-only controls. A pattern of delayed apoptosis was evident in these 7 lines, with secondary apoptotic peaks (∼ 8.0%) occurring at 24 hours post-RT+C225. Time course viability measurements revealed a steady decrease in viable tumor cells in these responsive cell lines from 75% at 6 hours post-RT+C225 to 20% at 7 days. Clonogenic survival was also diminished in these 7 lines

  19. Radiographic estimation in seropositive and seronegative rheumatoid arthritis.

    Science.gov (United States)

    Sahatçiu-Meka, Vjollca; Rexhepi, Sylejman; Manxhuka-Kërliu, Suzana; Rexhepi, Mjellma

    2011-08-01

    Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis, diagnosed with negative rheumatoid factor tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis (RA). Our aim was to establish a scientific comparative analysis between seronegative and seropositive rheumatoid arthritis, regarding some radiological and clinical parameters, applied for the first time on patients from Kosovo. Two hundred fifty patients with rheumatoid arthritis according to the American College of Rheumatology criteria were retrospectively studied by analysis the radiographic damage and clinical parameters of the disease, using a data base. All examinees were between 25-60 years of age (Xb=49.96, SD=10.37) with disease duration between 1-27 years (Xb = 6.41, SD=6.47). All patients underwent a standardised evaluation radiographs. Baseline standardised poster anterior radiographs of hands and feet and radiographs of other joints, depending on indications, were assessed. Erythrocyte sedimentation rate values correlated with the radiological damages and statistical difference was found for seronegative subset (r=0.24, p<0.01). Longer duration of the disease resulted in the increase of radiological changes in both subsets (r=0.66, p<0.01) seronegative, (r=0.49, p<0.01) seropositive. Anatomic changes of IInd and IIIrd level were nearly equally distributed in both subsets, 76 (60.8%) seronegative, 75 (60%) seropositive. Radiological damages are nearly equal in both subsets, elevate in relation to the duration of the disease and correlate with ESR values. Regarding the sero-status, differences within sex, with some exceptions, are not relevant. Although there are some definite quantitative and qualitative differences regarding sero-status, obviously there is a great deal of overlap between the two groups.

  20. Radiographic estimation in seropositive and seronegative rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Vjollca Sahatçiu-Meka

    2011-08-01

    Full Text Available Long since it have been suggested that a subpopulation of patients with rheumatoid arthritis, diagnosed with negative rheumatoid factor tests, represents a clinical entity quite distinct from that of seropositive rheumatoid arthritis (RA. Our aim was to establish a scientific comparative analysis between seronegative and seropositive rheumatoid arthritis, regarding some radiological and clinical parameters, applied for the first time on patients from Kosovo. Two hundred fifty patients with rheumatoid arthritis according to the American College of Rheumatology criteria were retrospectively studied by analysis the radiographic damage and clinical parameters of the disease, using a data base. All examinees were between 25-60 years of age (Xb=49.96, SD=10.37 with disease duration between 1-27 years (Xb = 6.41, SD=6.47. All patients underwent a standardised evaluation radiographs. Baseline standardised poster anterior radiographs of hands and feet and radiographs of other joints, depending on indications, were assessed. Erythrocyte sedimentation rate values correlated with the radiological damages and statistical difference was found for seronegative subset (r=0.24, p<0.01. Longer duration of the disease resulted in the increase of radiological changes in both subsets (r=0.66, p<0.01 seronegative, (r=0.49, p<0.01 seropositive. Anatomic changes of IInd and IIIrd level were nearly equally distributed in both subsets, 76 (60.8% seronegative, 75 (60% seropositive. Radiological damages are nearly equal in both subsets, elevate in relation to the duration of the disease and correlate with ESR values. Regarding the sero-status, differences within sex, with some exceptions, are not relevant. Although there are some definite quantitative and qualitative differences regarding sero-status, obviously there is a great deal of overlap between the two groups.

  1. Iatrogenic T-Cell Lymphoma with Associated Hemophagocytic Lymphohistiocyotsis in a Patient with Long-Standing Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    X. A. Andrade

    2018-01-01

    Full Text Available Patients with rheumatoid arthritis are at increased risk of hematological malignancies, especially when exposed to immunosuppressive therapy. The mechanisms of lymphomagenesis remain poorly understood but factors implicated include high disease activity, exposure to antitumoral necrosis factor medications, and Epstein–Barr virus infection. Lymphoid malignancies of T-cell origin are uncommon in patients with rheumatoid arthirits. Clinical presentation with associated hemophagocytic lymphohistiocyotsis is rare and confers a poor prognosis. This case report illustrates a case of a patient with long-standing rheumatoid arthritis and an iatrogenic peripheral T-cell lymphoma with secondary hemophagocytic lymphohistiocytosis who achieved a complete response after intensive chemotherapy.

  2. Arthroscopic Synovectomy of Wrist in Rheumatoid Arthritis.

    Science.gov (United States)

    Shim, Jae Woo; Park, Min Jong

    2017-11-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disorder affecting multiple joints. Wrist involvement is common. Patients with persistent symptoms despite medical management are candidates for surgery. Synovectomy can provide pain relief and functional improvement for rheumatoid wrist. Arthroscopic synovectomy is a safe and reliable method, with minimal postoperative morbidity. This article reviews the role, technique, and results of arthroscopic synovectomy in the rheumatoid wrist. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Atypical Localized Rheumatoid Nodule: Case Report

    Directory of Open Access Journals (Sweden)

    KORHAN BARIS BAYRAM

    2015-01-01

    Full Text Available Rheumatoid nodules can be seen in about 30% of patiens with rheumatoid arthritis. They are occasionally localized subcutaneous, but they can rarely seen in visceral organs. Their appearance can be confused with many clinical conditions when they have atypical localizations. To exclude the presence of a malignancy, these lesions should always be investigated. We aimed to discuss a patient with rheumatoid nodule localized in close neighborhood of hyoid bone, presumed as malignancy.

  4. rheumatoid arthritis health outcome

    African Journals Online (AJOL)

    2004-12-04

    Dec 4, 2004 ... socio-demographic factors and psychological factors .... ple regression analysis was used to test the health-sustaining function of ..... Bless C, Higson-Smith C. Fundamentals of Social Research Methods. An African.

  5. Rheumatoid arthritis as psychic problem

    Directory of Open Access Journals (Sweden)

    Jiří Kaas

    2014-01-01

    Full Text Available The article deals with the issue of psychic problems of rheumatoid arthritis patients. Rheumatoid arthritis is a chronic, inflammatory motor system disease with comprehensive impact on the patient's life. The disease is often considered an exclusively physical disease. But such approach is insufficient because the disease is accompanied by motor limitations of different intensities, by pain and by fatigue that cause considerable exhaustion to the patient. The patients often must give up their hobbies and in some cases even their jobs. In most serious cases, even common daily activities including self–servicing actions become an obstacle to the patient. It is therefore logical that the psyche of a patient with such disease is considerably strained. One of the partial goals of the study consisted in mapping the subjectively perceived quality of life of rheumatoid arthritis patients in facet 8, "negative feelings", and in ascertaining whether there is statistically significant relation to facets 1, "pain and discomfort", and 2, "energy and fatigue". Another goal consisted in comparing the subjectively perceived quality of life between men and women with rheumatoid arthritis, as well as between population of rheumatoid arthritis patients and control healthy population. The study was implemented within the research project of the Grant Agency of the University of South Bohemia in České Budějovice number 120/2012/S, „Reflection of quality of life in nursing", under use of two standardized questionnaires, WHOQOL–100 and HAQ. This article presents exclusively the data acquired based on the WHOQOL–100 questionnaire. The research set consisted of patients suffering from rheumatoid arthritis from all over the Czech Republic. The size of the set was determined by a statistician at 200 individuals suffering from the disease, in a ratio of 150 women and 50 men. The selection set was derived from the basic set of rheumatoid arthritis patients and

  6. Rheumatoid arthritis as psychic problem

    Directory of Open Access Journals (Sweden)

    Jiří Kaas

    2014-12-01

    Full Text Available The article deals with the issue of psychic problems of rheumatoid arthritis patients. Rheumatoid arthritis is a chronic, inflammatory motor system disease with comprehensive impact on the patient's life. The disease is often considered an exclusively physical disease. But such approach is insufficient because the disease is accompanied by motor limitations of different intensities, by pain and by fatigue that cause considerable exhaustion to the patient. The patients often must give up their hobbies and in some cases even their jobs. In most serious cases, even common daily activities including self-servicing actions become an obstacle to the patient. It is therefore logical that the psyche of a patient with such disease is considerably strained. One of the partial goals of the study consisted in mapping the subjectively perceived quality of life of rheumatoid arthritis patients in facet 8, "negative feelings", and in ascertaining whether there is statistically significant relation to facets 1, "pain and discomfort", and 2, "energy and fatigue". Another goal consisted in comparing the subjectively perceived quality of life between men and women with rheumatoid arthritis, as well as between population of rheumatoid arthritis patients and control healthy population. The study was implemented within the research project of the Grant Agency of the University of South Bohemia in České Budějovice number 120/2012/S, "Reflection of quality of life in nursing", under use of two standardized questionnaires, WHOQOL-100 and HAQ. This article presents exclusively the data acquired based on the WHOQOL-100 questionnaire. The research set consisted of patients suffering from rheumatoid arthritis from all over the Czech Republic. The size of the set was determined by a statistician at 200 individuals suffering from the disease, in a ratio of 150 women and 50 men. The selection set was derived from the basic set of rheumatoid arthritis patients and can

  7. Is Hearing Impairment Associated with Rheumatoid Arthritis?

    DEFF Research Database (Denmark)

    Emamifar, Amir; Bjoerndal, Kristine; Jensen Hansen, Inger Marie

    2016-01-01

    BACKGROUND: Rheumatoid arthritis (RA) is a systemic, inflammatory disease that affects 1% of the population. The auditory system may be involved during the course of disease; however the association of RA and hearing impairment has not been clearly defined. OBJECTIVE: The objective of this review...... is to evaluate published clinical reports related to hearing impairment in patients with RA. Furthermore, we discuss possible pathologies and associated factors as well as new treatment modalities. METHOD: A thorough literature search was performed using available databases including Pubmed, Embase, Cochrane...... and ComDisDome to cover all relative reports. The following keywords were used: hearing loss, hearing difficulties, hearing disorders, hearing impairment, sensorineural hearing loss, conductive hearing loss, mixed hearing loss, autoimmune hearing loss, drug ototoxicity, drug-induced hearing loss, hearing...

  8. VARIAR Study: Assessment of short-term efficacy and safety of rituximab compared to an tumor necrosis factor alpha antagonists as second-line drug therapy in patients with rheumatoid arthritis refractory to a first tumor necrosis factor alpha antagonist.

    Science.gov (United States)

    Torrente-Segarra, Vicenç; Acosta Pereira, Asunción; Morla, Rosa; Ruiz, José Miguel; Clavaguera, Teresa; Figuls, Ramon; Corominas, Hector; Geli, Carme; Roselló, Rosa; de Agustín, Juan José; Alegre, Cayetano; Pérez, Carolina; García, Angel; Rodríguez de la Serna, Arturo

    to compare the short-term efficacy and safety of rituximab (RTX) therapy versus anti-TNF in rheumatoid arthritis (RA) patients after discontinuation of a first anti-TNF agent. prospective observational multicenter study in the clinical practice setting, involving patients with severe RA refractory to a first anti-TNF agent, who received either RTX or a second anti-TNF (2TNF), comparing the efficacy endpoints, EULAR response (Good/Moderate) and safety at 6 months. 103 patients enrolled, 82 completed 6-month follow-up, 73.7% women. Baseline data for RTX and 2TNF groups, respectively: TJC, 8.6 and 6.6; SJC, 8.8 and 7.5; DAS28 score, 5.45 (±1.28) and 5.18 (±1.21) (p=0.048), ESR, 41 and 38.7mmHg; and HAQ, 1.2 and 1.0. Improvement was observed in all parameters, with no significant differences (except for a more marked reduction in ESR with RTX). There were no serious adverse events. RTX use as second-line therapy after anti-TNF failure led to improvements in the efficacy and functional variables at 6 months, with no serious adverse events. These results were comparable to those observed in patients who used a second anti-TNF agent in the same clinical scenario. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  9. Relationship between hyperthyroidism and monoclonal gammapathy

    International Nuclear Information System (INIS)

    Canas, Carlos Alberto

    2007-01-01

    A 66-year-old man with primary hyperparathyroidism (PHPT) and monoclonal gammapathy associated to it of uncertain significance (MGUS). A possible pathogenic relationship between HPTP and MGUS is analyzed. Interleukin 6 could play a pivotal role.

  10. Monoclonal antibody therapy of inflammatory bowel disease

    NARCIS (Netherlands)

    van Deventer, S. J.; Camoglio, L.

    1997-01-01

    Animal models of inflammatory bowel disease have provided insight in the regulation of mucosal inflammation. This has resulted in novel therapeutic approaches that specifically target a single inflammatory mediator. Monoclonal antibody therapy has been used in steroid refractory Crohn's disease

  11. Cystic form of rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Dijkstra, P.F.; Gubler, F.M.; Maas, A.

    1988-10-01

    A nonerosive form of rheumatoid arthritis (R.A.) was found in 62 patients out of 660 patients with R.A.. These 62 patients exhibit slowly progressive cystic changes in about the same joints in which usually erosions develop in classic R.A.. The E.S.R. is often low, half of the patients remained seronegative and there are 35 males and 27 females in the group. A smaller group of 15 out of these patients could be followed from a stage wherein the radiographs were normal to a stage of extensive cystic changes, over a period of at least 6 years. An attempt is made to delineate this group within the rheumatoid arthritis disease entity.

  12. Monoclonal for cancer detection and therapy

    International Nuclear Information System (INIS)

    Baldwin, R.W.; Byers, V.S.

    1985-01-01

    This book contains 18 chapters. Some of the chapter titles are: Monoclonal Antibodies to Breast Cancer and Their Application; Clinical Applications of Radioimmunolocalisation; Localisation of Cancer of the Ovary and Metastases Using 123 I-labelled Monoclonal Antibody HMFG-2 Compared to Surgical Findings; Interest of Globotriaosylceramide Membrane Antigen as Target for Immunotoxins; and Analysis, Results and Future Prospective of the Therapeutic Use of Radiolabeled Antibody in Cancer Therapy

  13. EFFICACY OF RECURRENT RITUXIMAB TREATMENT IN PATIENT WITH SEVERE REFRACTORY SYSTEMIC JUVENILE RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    E.I. Alexeeva

    2011-01-01

    Full Text Available The article contains clinical case description of a severe systemic juvenile rheumatoid arthritis, that was refractory to classic immunosuppressant therapy. The disease was characterized by such extraarticular manifestations as fever, lymphadenopathy,  hepatosplenomegaly, polyserositis, generalized joint involvement and high activity in lab tests. As a result of severe clinical course of the disease, patients develop bilateral aseptic bone necrosis in coxofemoral joints and coxarthrosis. Against the background of glucocorticosteroid treatment the patient has developed hormone-dependency and hormone resistance. Inclusion into the treatment of anti-CD20 monoclonal antibodies (rituximab has stopped systemic manifestations of the disease, inflammation in the joints, normalized lab activity rates. The positive therapeutic effect allowed to perform surgery due to bilateral coxarthrosis. These results show that rituximab is highly effective in children with systemic juvenile rheumatoid arthritis, that is resistant to classic immunosupressants and glucocorticoides. Key words: children, systemic juvenile rheumatoid arthritis, rituximab, recurrent treatment, prosthetics, hip joint. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 157–163.

  14. Antibodies and Selection of Monoclonal Antibodies.

    Science.gov (United States)

    Hanack, Katja; Messerschmidt, Katrin; Listek, Martin

    Monoclonal antibodies are universal binding molecules with a high specificity for their target and are indispensable tools in research, diagnostics and therapy. The biotechnological generation of monoclonal antibodies was enabled by the hybridoma technology published in 1975 by Köhler and Milstein. Today monoclonal antibodies are used in a variety of applications as flow cytometry, magnetic cell sorting, immunoassays or therapeutic approaches. First step of the generation process is the immunization of the organism with appropriate antigen. After a positive immune response the spleen cells are isolated and fused with myeloma cells in order to generate stable, long-living antibody-producing cell lines - hybridoma cells. In the subsequent identification step the culture supernatants of all hybridoma cells are screened weekly for the production of the antibody of interest. Hybridoma cells producing the antibody of interest are cloned by limited dilution till a monoclonal hybridoma is found. This is a very time-consuming and laborious process and therefore different selection strategies were developed since 1975 in order to facilitate the generation of monoclonal antibodies. Apart from common automation of pipetting processes and ELISA testing there are some promising approaches to select the right monoclonal antibody very early in the process to reduce time and effort of the generation. In this chapter different selection strategies for antibody-producing hybridoma cells are presented and analysed regarding to their benefits compared to conventional limited dilution technology.

  15. Two cases of rheumatoid meningitis.

    Science.gov (United States)

    Magaki, Shino; Chang, Edward; Hammond, Robert R; Yang, Isaac; Mackenzie, Ian R A; Chou, Benedict T; Choi, Soo I; Jen, Joanna C; Pope, Whitney B; Bell, David A; Vinters, Harry V

    2016-02-01

    Central nervous system (CNS) involvement by rheumatoid arthritis (RA) in the form of rheumatoid meningitis (RM) is rare and most commonly occurs in the setting of longstanding severe RA. Due to a wide range of clinical presentations and nonspecific laboratory findings, it presents a diagnostic challenge often requiring brain biopsy. Only a few histopathologically confirmed cases have been described in the literature. Our aim is to describe two cases of RM and review the literature. The first case is of a previously healthy 37-year-old man who presented with severe headaches and focal neurologic deficits. Magnetic resonance imaging demonstrated abnormal leptomeningeal enhancement in the left frontal and parietal sulci. The second case is of a 62-year-old woman with a history of mild chronic joint pain who presented with confusion, personality changes and seizures. Both patients ultimately underwent brain biopsy which demonstrated RM on pathologic examination. Administration of corticosteroids resulted in significant clinical improvement in both cases. To our knowledge, our unusual case of RM in the young man is the fifth reported case of rheumatoid meningitis in a patient with no prior history of RA. Such an atypical presentation makes diagnosis even more difficult and highlights the need for awareness of this entity in the diagnostic consideration of a patient presenting with unexplained neurologic symptoms. Our literature review underscores the clinical and pathologic heterogeneity of CNS involvement in RA. © 2015 Japanese Society of Neuropathology.

  16. Association of levels of antibodies against citrullinated cyclic peptides and citrullinated α-enolase in chronic and aggressive periodontitis as a risk factor of Rheumatoid arthritis: a case control study.

    Science.gov (United States)

    Reichert, Stefan; Schlumberger, Wolfgang; Dähnrich, Cornelia; Hornig, Nora; Altermann, Wolfgang; Schaller, Hans-Günter; Schulz, Susanne

    2015-08-29

    Periodontal disease could be a risk factor for rheumatoid arthritis (RA). It is assumed that the bacterial strain Porphyromonas gingivalis mediates citrullination of host peptides and thereby the generation of RA-associated autoantibodies in genetically predisposed individuals. For that reason non-RA individuals who suffered from generalized aggressive (GAgP, N = 51) and generalized chronic periodontitis (GChP, N = 50) were investigated regarding the occurrence of antibodies against citrullinated cyclic peptides (anti-CCP) and citrullinated α-enolase peptide-1 (anti-CEP-1) in comparison to non-RA non-periodontitis controls (N = 89). Furthermore, putative associations between infections with five periodontopathic bacteria or expression of certain human leucocyte antigens (HLA) to these autoantibodies were investigated. The presence of anti-CCP and anti-CEP-1 in plasma samples was conducted with enzyme linked immunosorbent assay. Subgingival plaque specimens were taken from the deepest pocket of each quadrant and pooled. For detection of DNA of five periodontopathic bacteria PCR with sequence specific oligonucleotides was carried out. Low resolution HLA typing was carried out with PCR with sequence specific primers. Differences between patients and controls were assessed using Chi square test with Yates correction or Fisher`s exact test if the expected number n in one group was GChP and two controls (2.2%, pFisher = 0.662) were positive for anti-CEP-1 whereas no study participant was anti-CCP positive. Individuals with P. gingivalis were slightly more often anti-CEP-1 positive in comparison to individuals without P. gingivalis (3.2 vs. 1.1%, pFisher = 0.366). Carrier of HLA-DQB1*06 or the HLA combination DRB1*13; DRB3*; DQB1*06 were slightly more anti-CEP-1 positive (6.1 and 4.3%) than no carriers (0.7 and 0%, pFisher 0.053). GAgP and GChP and the presence of periodontopathic bacteria are not associated with an increased risk for occurrence of anti-CCP and anti

  17. Systemic radiotherapy with monoclonal antibodies

    International Nuclear Information System (INIS)

    Sautter-Bihl, M.L.; Matzku, S.; Bihl, H.

    1993-01-01

    In this experimental study, feasibility and efficiency of systematic radiotherapy with the I-131 labelled monoclonal antibody BW575/9 (radioimmunotherapy) are investigated using human SK-N-SH neuroblastoma transplated into nude mice. Series of six nude mice were treated with intravenous application of 400 μCi (group 1), 700 μCi (group 2) of the I-131 labelled and of the unlabelled MAb (group 3). An untreated group (group 4) served as control. Tumors of group (3) and (4) showed an identical growth. In group (1), tumor growth was arrested for seven days. In group (2), the tumor showed complete regression after eight days which lasted for 55 days. Thereafter, the tumor started to regrow. This growth characteristics are correlated with the doses achieved in the tumor using a medical radiation dose (MIRD) formulation. The biodistribution data necessary for MIRD calculation were obtained by previously performed experiments with the I-125 labelled MAb. The doses assessed in the tumor turned out to be five to ten times greater than those in normal tissues (liver, bone, etc.) These results confirm feasibility, selectivity and efficiency of radioimmunotherapy in the above described model. Moreover, this in vivo model seems suitable for further investigations concerning fundamental issues of radioimunotherapy. (orig.) [de

  18. [Dyslipidemia and atherogenic risk in patients with rheumatoid arthritis].

    Science.gov (United States)

    Batún Garrido, José Antonio de Jesús; Olán, Francisco; Hernández Núñez, Éufrates

    2016-01-01

    Dyslipidaemia is one of the main risk factors for atherosclerotic cardiovascular disease. Patients with rheumatoid arthritis have 2-3 times more cardiovascular risk, which is partly due to the pattern of lipids which increase the atherogenic index. A descriptive, cross-sectional, observational and prospective study was conducted on 82 patients, selected for their lipid profile. Variables associated with the disease and the drugs used were recorded. Atherogenic risk was calculated, with Chi square being used for categorical variables, and the Mann-Whitney test for the continuous ones. The dyslipidaemia frequency was 54.9%. The most frequent age range of dyslipidaemia was between 51 and 60 years. Patients with type i obesity had a higher frequency of dyslipidaemia. Less dyslipidaemia was found with a lower rate of disease activity. Patients with cyclic citrullinated anti-peptide antibodies and positive rheumatoid factor, erythrocyte sedimentation rate>13mm or CRP>2mg/L had a higher frequency of dyslipidaemia. The mean Castelli atherogenic index was 4.36, the index of Kannel was 2.59, and triglycerides/HDL-c ratio was 3.83.Patients with dyslipidaemia showed a higher frequency of positive rheumatoid factor (P=.0008), and those patients who were taking hydroxychloroquine had a lower frequency of dyslipidaemia P=.03. Patients with rheumatoid arthritis have a pro-atherogenic lipid profile. It is important to know this and treat it to reduce cardiovascular risk. Copyright © 2016 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  19. Use of AN Eosinophil Specific Monoclonal Antibody in Assessing Eosinophil Function.

    Science.gov (United States)

    Minkoff, Marjorie Sue

    A monoclonal antibody to an eosinophil specific determinant is very important in assessing eosinophil function during helminthic infection. Eosinophils induced by Schistosoma mansoni infection in BALB/c mice were used to induce C57B1/6 immunocytes for production of hybridomas secreting eosinophil monoclonal antibodies. These antibodies were shown to react with an eosinophil surface epitope but not with neutrophils or macrophages as determined by ELISA, immunodiffusion, immunofluorescence, and immunoblot assay. Affinity chromatography with eosinophil chemotactic factor-sepharose consistently selected out a { rm M_ R} 67,000 protein from solubilized eosinophil membrane antigens but not from neutrophil and macrophage antigens. In vitro studies showed that the eosinophil-specific monoclonal antibodies abrogated antibody-dependent eosinophil -mediated killing of S. mansoni schistosomula using mouse, rat or human eosinophils. Neutrophil and macrophage killing activities were unaffected. The monoclonal antibodies effected complement-dependent lysis of mouse and rat eosinophils but not of human eosinophils. ECF-treated eosinophils showed enhanced killing of schistosomula which was blocked by the monoclonal antibody. Murine and human eosinophils preincubated with monoclonal antibody exhibited decreased chemotaxis to ECF at optimal chemotactic concentrations. The monoclonal antibody also blocked eosinophil binding to ECF- sepharose beads. In vivo induction of peripheral blood eosinophilia by injection of S. mansoni eggs was suppressed by injections of monoclonal antibodies 2CD13 and 2QD45 in mouse and rat experimental models. Eosinophilia induced by keyhole limpet hemocyanin- cyclophosphamide treatment was also suppressed by monoclonal antibody in both murine and rat systems. Pulmonary granulomas in mice given egg injection and monoclonal antibody were smaller and contained fewer eosinophils than those granulomas from mice given eggs only. In immuno-biochemical studies, the

  20. Short- and long-term efficacy of intra-articular injections with betamethasone as part of a treat-to-target strategy in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Hetland, Merete Lund; Østergaard, Mikkel; Ejbjerg, Bo

    2012-01-01

    To investigate the short-term and long-term efficacy of intra-articular betamethasone injections, and the impact of joint area, repeated injections, MRI pathology, anticyclic citrullinated peptide (CCP) and immunoglobulin M rheumatoid factor (IgM-RF) status in patients with early rheumatoid arthr...

  1. Rheumatoid arthritis in the hand. Chapter 9

    International Nuclear Information System (INIS)

    Weston, W.J.

    1979-01-01

    Rheumatoid arthritis is primarily a disease of the synovial membrane. To demonstrate synovial changes it is necessary to show adequate detail of the soft tissue. This is best obtained by using industrial film and by hand-processing. The anatomy of the hand and the radiological appearance of rheumatoid arthritis are described. (author)

  2. Targeted treatment in early rheumatoid arthritis

    NARCIS (Netherlands)

    Klarenbeek, Naomi Bertine

    2013-01-01

    With the implementation of new treatment options, including biologicals and the early, agressive start of target-steered treatment the outlook for rheumatoid arthritis patients improved considerably the past decades. This thesis describes several aspects of modern rheumatoid arthritis treatment from

  3. Antitumor efficacy of triple monoclonal antibody inhibition of epidermal growth factor receptor (EGFR) with MM151 in EGFR-dependent and in cetuximab-resistant human colorectal cancer cells

    Science.gov (United States)

    Napolitano, Stefania; Martini, Giulia; Martinelli, Erika; Della Corte, Carminia Maria; Morgillo, Floriana; Belli, Valentina; Cardone, Claudia; Matrone, Nunzia; Ciardiello, Fortunato; Troiani, Teresa

    2017-01-01

    Purpose We investigated the effect of triple monoclonal antibody inhibition of EGFR to overcome acquired resistance to first generation of anti-EGFR inhibitors. Experimental design MM151 is a mixture of three different monoclonal IgG1 antibodies directed toward three different, non-overlapping, epitopes of the EGFR. We performed an in vivo study by using human CRC cell lines (SW48, LIM 1215 and CACO2) which are sensitive to EGFR inhibitors, in order to evaluate the activity of MM151 as compared to standard anti-EGFR mAbs, such as cetuximab, as single agent or in a sequential strategy of combination MM151 with irinotecan (induction therapy) followed by MM151 with a selective MEK1/2 inhibitor (MEKi) (maintenance therapy). Furthermore, the ability of MM151 to overcome acquired resistance to cetuximab has been also evaluated in cetuximab-refractory CRC models. Results MM151 shown stronger antitumor activity as compared to cetuximab. The maintenance treatment with MM151 plus MEKi resulted the most effective therapeutic modality. In fact, this combination caused an almost complete suppression of tumor growth in SW48, LIM 1215 and CACO2 xenografts model at 30 week. Moreover, in this treatment group, mice with no evidence of tumor were more than double as compared to single agent treated mice. Its superior activity has also been demonstrated, in cetuximab-refractory CRC models. Conclusions These results provide experimental evidence that more efficient and complete EGFR blockade may determine better antitumor activity and could contribute to prevent and/or overcome acquired resistance to EGFR inhibitors. PMID:29137301

  4. A population study on rheumatoid arthritis in Lesotho, southern Africa.

    Science.gov (United States)

    Moolenburgh, J D; Valkenburg, H A; Fourie, P B

    1986-01-01

    Motivated by the results of a hospital study on rheumatoid arthritis (RA) in Lesotho (southern Africa) a survey of inflammatory polyarthritis (IP) and RA was undertaken in a sample of the rural population of that country. Contrary to expectations the prevalence of IP grades 2-4 (definite disease) was low (0.4%) and equal in both sexes, while probable and definite RA combined (American Rheumatism Association (ARA) criteria) occurred in 1.8% of both males and females. RA was slightly more severe than in other rural African Negro studies but less so when compared with the disease condition of the patients observed in the hospital study. Rheumatoid factor and particularly that directed against heterologous antigen occurred in 41% of the RA patients and in 16% of the controls. Two thirds of the definite cases and 29% of the combined probable and definite group showed radiological abnormalities. PMID:3740998

  5. TNFα blockers and infectious risk in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    S. Todesco

    2011-06-01

    Full Text Available Patients suffering from rheumatoid arthritis have increased risk of infections when compared with general population. The risk depends directly from disease activity and severity. Furthermore, risk increases with aging, immunosuppressive agents and comorbidities such as diabetes, pulmonary and cardiac diseases. In particular corticosteroids, even at low doses, are a major risk factor. Due to disease related risk it is difficult to separate the risk deriving from the use of TNF alpha blockers. Data from clinical trials, meta-analysis and national registers are somewhat contradictory. In patients with rheumatoid arthritis on routine follow-up, treatment with TNF alpha blockers seems to carry an increased risk of infections compared to traditional DMARDs but not associated with increased risk of overall serious infection. Physicians should carefully monitor for signs of infection when using TNF alpha blockers, particularly shortly after treatment initiation.

  6. Isotypes of Epstein-Barr virus antibodies in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Westergaard, Marie Wulff; Draborg, Anette Holck; Troelsen, Lone

    2015-01-01

    In order to study the humoral immune response against Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to compare it with the two major autoantibody types in RA, plasma samples from 77 RA patients, 28 patients with systemic lupus erythematosus (SLE), and 28 healthy controls...... and percentages of positives of IgG/IgA/IgM against the early lytic EBV antigen diffuse (EAD) were also found in RA patients compared to HCs but were highest in SLE patients. Furthermore, associations between the elevated EBNA-1 IgA and EBNA-1 IgM levels and the presence of IgM and IgA rheumatoid factors (RFs...

  7. Lower limb joint replacement in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Clement Nicholas D

    2012-06-01

    Full Text Available Abstract Introduction There is limited literature regarding the peri-operative and surgical management of patients with rheumatoid disease undergoing lower limb arthroplasty. This review article summarises factors involved in the peri-operative management of major lower limb arthroplasty surgery for patients with rheumatoid arthritis. Methods We performed a search of the medical literature, using the PubMed search engine (http://www.pubmed.gov. We used the following terms: ‘rheumatoid’ ‘replacement’ ‘arthroplasty’ and ‘outcome’. Findings The patient should be optimised pre-operatively using a multidisciplinary approach. The continued use of methotrexate does not increase infection risk, and aids recovery. Biologic agents should be stopped pre-operatively due the increased infection rate. Patients should be made aware of the increased risk of infection and periprosthetic fracture rates associated with their disease. The surgical sequence is commonly hip, knee and then ankle. Cemented total hip replacement (THR and total knee replacement (TKR have superior survival rates over uncemented components. The evidence is not clear regarding a cruciate sacrificing versus retaining in TKR, but a cruciate sacrificing component limits the risk early instability and potential revision. Patella resurfacing as part of a TKR is associated with improved outcomes. The results of total ankle replacement remain inferior to THR and TKR. RA patients achieve equivalent pain relief, but their rehabilitation is slower and their functional outcome is not as good. However, the key to managing these complicated patients is to work as part of a multidisciplinary team to optimise their outcome.

  8. Rheumatoid arthritis in the United Arab Emirates.

    Science.gov (United States)

    Badsha, Humeira; Kong, Kok Ooi; Tak, Paul P

    2008-06-01

    Studies have shown that patients with rheumatoid arthritis (RA) in the Middle East have delayed diagnosis and low disease-modifying anti-rheumatic drug (DMARD) utilization. We describe the characteristics and treatments of consecutive RA patients presenting to a new musculoskeletal clinic in Dubai, United Arab Emirates (UAE). Demographic and clinical data were collected over a 10-month period at the first visit to our clinic for patients meeting the American College of Rheumatology (ACR) criteria for RA. A total of 100 patients were seen: (average +/- SD) age 42.2 +/- 12.3 years; female 87%; Arabs 38%, Indian 36%, Caucasian and others 26%; 73% rheumatoid-factor positive; years since diagnosis: 3.9 +/- 5.7; lag time between symptom onset to diagnosis 1.2 +/- 1.3 years and lag time to first DMARD was 1.6 +/- 2.0 years. Mean tender joint count was 8.9 +/- 7.9, mean swollen joint count 9.0 +/- 7.6, mean patient's global assessment of disease activity 57.4 +/- 25.0 mm, mean ESR 33 +/- 25 mm/h, mean DAS28 5.2 +/- 1.6, physician global assessment 55.0 +/- 23.8. Only 43% were on DMARDs (25% MTX, 5% TNF blockers). Among the patients who were not on DMARD, only 28.1% had disease duration less than 1 year (p = <0.01). Erosions were present in 55.2% of patients with available X-rays, and deformities in 26% of patients. There were no racial differences in disease characteristics. The UAE has a unique population with many races residing in the country. Among the first 100 consecutive patients seen at our clinic, there were no significant differences in disease characteristics with the majority of the patients having very active disease, delayed diagnosis, and not being treated with DMARDs.

  9. Ghrelin gene polymorphisms in rheumatoid arthritis.

    Science.gov (United States)

    Ozgen, Metin; Koca, Suleyman Serdar; Etem, Ebru Onalan; Yuce, Huseyin; Aydin, Suleyman; Isik, Ahmet

    2011-07-01

    Ghrelin, an endogenous orexigenic peptide, has anti-inflammatory effects, down-regulates pro-inflammatory cytokines, and its altered levels are reported in various inflammatory diseases. The human preproghrelin (ghrelin/obestatin) gene shows several single nucleotide polymorphisms (SNPs) including Arg51Gln, Leu72Met, Gln90Leu, and A-501C. The aim of this study was to investigate the frequency, and clinical significance, of these four SNPs in a small cohort of Turkish patients with rheumatoid arthritis (RA). The study included 103 patients with RA and 103 healthy controls. In the RA group, disease activity and disease-related damage were assessed using the Disease Activity Score-28 (DAS-28), and the modified Larsen scoring (MLS) methods. In all the participants, genomic DNA was isolated and genotyped by polymerase chain reaction and restriction fragment length polymorphism analysis. The frequencies of ghrelin gene SNPs were 82.5 and 79.6% in the RA and control groups, respectively, and there were no significant differences in terms of genotype distributions and allele frequencies for these four SNPs between the groups. However, the A-501C SNP was found to be associated with early disease onset, and Gln90Leu SNP with less frequent rheumatoid factor positivity, in the RA group. A-501C SNP is associated with earlier onset of RA suggesting that genetic variations in the ghrelin gene may have an impact on RA. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  10. A STUDY OF THE OCULAR MANIFESTATIONS OF RHEUMATOID ARTHRITIS AMONG PATIENTS PRESENTING TO A TERTIARY CENTRE

    Directory of Open Access Journals (Sweden)

    Dhanya Sukumaran

    2017-08-01

    Full Text Available BACKGROUND Rheumatoid Arthritis (RA is a chronic inflammatory disease of unknown aetiology marked by a symmetric peripheral polyarthritis. It is the most common form of chronic inflammatory arthritis and often results in joint damage and physical disability. The name is based on the term "rheumatic fever", an illness, which includes joint pain and is derived from the Greekword ῥεύμα-rheuma (nom., ῥεύματος-rheumatos (gen. ("flow, current". The suffix oid ("resembling" gives the translation as joint inflammation that resembles rheumatic fever. The first recognised description of rheumatoid arthritis was made in 1800 by Dr. Augustin Jacob Landré-Beauvais (1772-1840 of Paris. Because, it is a systemic disease, RA may result in a variety of extra-articular manifestations including fatigue, subcutaneous nodules, lung involvement, pericarditis, peripheral neuropathy, vasculitis and haematologic abnormalities. MATERIALS AND METHODS Patients who were diagnosed cases of rheumatoid arthritis attending the rheumatology clinic were referred to the Ophthalmology OPD in Government Medical College, Thrissur, for detailed eye examination. RESULTS The study was conducted in 100 patients (88 females and 12 males. Rheumatoid Factor (RF was found to be positive in 60 patients (60%, presence of dry eye did not correlate with rheumatoid positivity (Fishers exact test- the two-tailed P value = 0.4256. Through various tests, we concluded that there was aqueous deficiency in 61% and mucin deficiency in 46% of the patients. Other ocular manifestations present were- scleritis (2%, episcleritis (2% and keratomalacia (2%. CONCLUSION From the present study, we found out that extra-articular involvement of organs in rheumatoid arthritis is significant. The main ocular manifestations in rheumatoid arthritis found in our study were keratoconjunctivitis sicca, episcleritis, scleritis and keratomalacia. Though keratoconjunctivitis sicca was the most common, it did

  11. Blockade of Toll-like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures

    LENUS (Irish Health Repository)

    Nic An Ultaigh, Sinead

    2011-02-23

    Abstract Introduction The aim of this study was to examine the effect of blocking Toll-like receptor 2 (TLR2) in rheumatoid arthritis (RA) synovial cells. Methods RA synovial tissue biopsies, obtained under direct visualization at arthroscopy, were established as synovial explant cultures ex vivo or snap frozen for immunohistology. Mononuclear cell cultures were isolated from peripheral blood and synovial fluid of RA patients. Cultures were incubated with the TLR1\\/2 ligand, Pam3CSK4 (200 ng, 1 and 10 μg\\/ml), an anti-TLR2 antibody (OPN301, 1 μg\\/ml) or an immunoglobulin G (IgG) (1 μg\\/ml) matched control. The comparative effect of OPN301 and adalimumab (anti-tumour necrosis factor alpha) on spontaneous release of proinflammatory cytokines from RA synovial explants was determined using quantitative cytokine MSD multiplex assays or ELISA. OPN301 penetration into RA synovial tissue explants cultures was assessed by immunohistology. Results Pam3CSK4 significantly upregulated interleukin (IL)-6 and IL-8 in RA peripheral blood mononuclear cells (PBMCs), RA synovial fluid mononuclear cells (SFMCs) and RA synovial explant cultures (P < 0.05). OPN301 significantly decreased Pam3CSK4-induced cytokine production of tumour necrosis factor alpha (TNF-α), IL-1β, IL-6, interferon (IFN)-γ and IL-8 compared to IgG control in RA PBMCs and SFMCs cultures (all P < 0.05). OPN301 penetration of RA synovial tissue cultures was detected in the lining layer and perivascular regions. OPN301 significantly decreased spontaneous cytokine production of TNF-α, IL-1β, IFN-γ and IL-8 from RA synovial tissue explant cultures (all P < 0.05). Importantly, the inhibitory effect of OPN on spontaneous cytokine secretion was comparable to inhibition by anti-TNFα monoclonal antibody adalimumab. Conclusions These findings further support targeting TLR2 as a potential therapeutic agent for the treatment of RA.

  12. Gene therapy in animal models of rheumatoid arthritis: are we ready for the patients?

    NARCIS (Netherlands)

    Loo, F.A.J. van de; Smeets, R.L.L.; Berg, W.B. van den

    2004-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints, with progressive destruction of cartilage and bone. Anti-tumour necrosis factor-alpha therapies (e.g. soluble tumour necrosis factor receptors) ameliorate disease in 60-70% of patients with RA. However, the need for

  13. Drug delivery options to increase patient adherence and satisfaction in the management of rheumatoid arthritis – focus on subcutaneous tocilizumab

    Directory of Open Access Journals (Sweden)

    Nakashima Y

    2014-07-01

    Full Text Available Yasuharu Nakashima,1 Masakazu Kondo,2 Hisaaki Miyahara,3 Yukihide Iwamoto11Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan; 2Kondo Clinic of Rheumatology and Orthopaedic Surgery, Fukuoka, Japan; 3Department of Orthopaedic Surgery and Rheumatology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanAbstract: Rheumatoid arthritis (RA is a chronic, progressive, inflammatory disease associated with joint destruction. Tocilizumab (TCZ is a humanized monoclonal anti-interleukin-6 receptor antibody that was initially developed for use as an intravenous (IV infusion. Previous studies have shown that TCZ-IV is an important treatment option in patients with moderate-to-severe RA. A subcutaneous (SC formulation of 162 mg TCZ that was recently developed and approved provides an additional treatment option for RA patients. In the present review, we provide an update on the efficacy and safety of TCZ-SC, compared with TCZ-IV. The TCZ-SC doses of 162 mg every 2 weeks (q2w or weekly (qw were selected based on pharmacokinetic and pharmacodynamic studies. Both TCZ-SC q2w and qw regimens showed equivalent effects to TCZ-IV in most patients; however, the TCZ-SC qw regimen consistently showed a more rapid effect in terms of C-reactive protein normalization. Randomized controlled studies showed that TCZ-SC monotherapy or combined with disease-modifying antirheumatic drugs demonstrated comparable efficacy to TCZ-IV in patients who were both biologic-naïve and refractory to tumor necrosis factor inhibitors. TCZ-SC at both qw and q2w were generally well-tolerated for up to 24 weeks. There was a low rate of withdrawal due to adverse events, and their incidence was comparable with that seen with TCZ-IV. An injection site reaction was seen in approximately 10% of patients who received the subcutaneous formulation. In conclusion, although clinical results are still limited, the currently available evidence

  14. Identifying flares in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Bykerk, Vivian P; Bingham, Clifton O; Choy, Ernest H

    2016-01-01

    to flare, with escalation planned in 61%. CONCLUSIONS: Flares are common in rheumatoid arthritis (RA) and are often preceded by treatment reductions. Patient/MD/DAS agreement of flare status is highest in patients worsening from R/LDA. OMERACT RA flare questions can discriminate between patients with...... Set. METHODS: Candidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded. Concordance to identify flares...

  15. Treating rheumatoid arthritis to target

    DEFF Research Database (Denmark)

    Smolen, Josef S; Aletaha, Daniel; Bijlsma, Johannes W J

    2010-01-01

    BACKGROUND: Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). OBJECTIVE: /st> To develop recommendations for achieving optimal therapeutic outcomes in RA. METHODS....... Levels of evidence, strength of recommendations and levels of agreement were derived. RESULTS: The treat-to-target activity resulted in 10 recommendations. The treatment aim was defined as remission with low disease activity being an alternative goal in patients with long-standing disease. Regular follow...

  16. Biosimilar Monoclonal Antibodies for Inflammatory Bowel Disease: Current Comfort and Future Prospects.

    Science.gov (United States)

    Gecse, Krisztina B; Lakatos, Péter L

    2016-10-01

    Biosimilars are biologic medicines that enter the market after a patent for an original reference product expires. The European Medicines Agency (EMA) developed a stringent legislation process for biosimilar monoclonal antibodies, whereby similarity to the reference medicinal product in terms of quality characteristics, biological activity, clinical safety and efficacy must be demonstrated. Biosimilar infliximab CT-P13 was the first biosimilar monoclonal antibody to receive EMA marketing authorization, and further biosimilar molecules are being developed. The phase I and III clinical trials were conducted in ankylosing spondylitis and rheumatoid arthritis, and the use of CT-P13 in inflammatory bowel disease (IBD) was extrapolated on the results of these trials. Medical professionals were initially concerned about the reversed engineering process, the novel legal framework and the lack of clinical data in IBD. Emerging real-world data have confirmed the similarities between CT-P13 and the reference product in terms of efficacy, safety and immunogenicity in IBD. The cost reduction represented by biosimilars promotes industry competition and improves treatment access with sustained quality of care. This article reviews the existing and emerging clinical data for CT-P13 and a future perspective on biosimilar use in IBD.

  17. New monoclonal antibodies to rat testicular antigen, TEC-21

    Czech Academy of Sciences Publication Activity Database

    Hálová, Ivana; Dráberová, Lubica; Dráber, Petr

    2001-01-01

    Roč. 47, č. 5 (2001), s. 180-182 ISSN 0015-5500 R&D Projects: GA ČR GV312/96/K205; GA ČR GA204/00/0204; GA ČR GA310/00/0205; GA AV ČR IAA5052005; GA AV ČR IAA7052006; GA MŠk LN00A026 Keywords : Monoclonal antibody * lipid raft * testicular cells Subject RIV: EC - Immunology Impact factor: 0.519, year: 2001

  18. New monoclonal antibodies to rat testicular antigen, TEC-21

    Czech Academy of Sciences Publication Activity Database

    Hálová, Ivana; Dráberová, Lubica; Dráber, Petr

    2001-01-01

    Roč. 47, č. 5 (2001), s. 180-182 ISSN 0015-5500 R&D Projects: GA ČR GV312/96/K205; GA ČR GA204/00/0204; GA ČR GA310/00/0205; GA AV ČR IAA5052005; GA AV ČR IAA7052006; GA MŠk LN00A026 Institutional research plan: CEZ:AV0Z5052915 Keywords : monoclonal antibody * GPI-anchored * testicular antigen Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.519, year: 2001

  19. Monoclonal antibodies in oncology. Review article

    Energy Technology Data Exchange (ETDEWEB)

    Chan, S Y.T.; Sikora, K

    1986-05-01

    Monoclonal antibodies (MCAs) can be used to differentiate between normal and neoplastic cells and thus exploited for diagnostic and, ultimately, therapeutic gain. The evidence for the existence of human tumour antigens is reviewed. Several areas of diagnosis are already benefiting from the application of the monoclonal technology. Immunohistology can help the pathologist with difficult diagnostic problems. New classifications of lymphoma and leukaemia can be based on specific surface molecules. Similarly, the detection of shed tumour antigens is already established as part of the routine assessment of many patients with common solid tumours. Isotopically labeled monoclonal antibodies have been used to localise primary and metastatic tumours. The use of antibodies in this way is not only a promising diagnostic tool but also the first step in studying the possibility of arming antibodies to provide therapeutic agents. Such trials are currently in progress. 69 refs.; 7 figs.; 3 tabs.

  20. Rheumatoid arthritis: identifying and characterising polymorphisms using rat models

    Science.gov (United States)

    2016-01-01

    ABSTRACT Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans. PMID:27736747

  1. Anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis patients

    International Nuclear Information System (INIS)

    Fakhr, A.; Ahmed, M.; Bashir, M.; Hakim, F.; Basri, R.

    2017-01-01

    Objective: To detect the anti cyclic citrullinated peptide (Anti-CCP) antibody in rheumatoid arthritis (RA) patients to determine its diagnostic value in Pakistani patients. Study Design: Cross sectional study. Place and Duration of Study: Military Hospital (MH) Rawalpindi, from January 2013 to June 2015. Material and Methods: A total of 58 patients with complications of rheumatoid arthritis were recruited in the study using convenient sampling technique after their informed consent. Age and gender of the patients were recorded. Blood was collected from the patients subjected to ELISA based detection of anti-CCP and latex agglutination test for detection of Rheumatoid Factor (RF). Data obtained were analyzed using Microsoft excel 2010. Results: Among the fifty eight RA patients, 40 percent were males and 60 percent were females. Age ranged between 12 to 80 years (mean age 49.74 +- 16.81 years) of the males RA patients and was higher as compared to females (mean age 43.2 +-16.70 years). ELISA based detection of anti-CCP antibody showed that about 91 percent of RA patients were positive for anti CCP antibody. About 72 percent were positive for anti CCP antibody alone, 19 percent were positive for both anti-CCP and RF and 9 percent were positive for RF. Conclusion: The results concluded that a higher percentage of the RA patients are positive for anti-CCP antibody marking its importance as a diagnostic marker. Anti-CCP has more sensitivity as compared to RF in RA patients. (author)

  2. Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis

    Science.gov (United States)

    Zhao, Xiaoyan; Okeke, Nwora Lance; Sharpe, Orr; Batliwalla, Franak M; Lee, Annette T; Ho, Peggy P; Tomooka, Beren H; Gregersen, Peter K; Robinson, William H

    2008-01-01

    Introduction There is increasing evidence that autoantibodies and immune complexes (ICs) contribute to synovitis in rheumatoid arthritis (RA), yet the autoantigens incorporated in ICs in RA remain incompletely characterised. Methods We used the C1q protein to capture ICs from plasma derived from human RA and control patients. Antibodies specific for immunoglobulin were used to detect ICs, and fibrinogen antibodies were used to detect fibrinogen-containing ICs. RA and control plasma were separated by liquid chromatography, and fractions then characterised by ELISA, immunoblotting and mass spectrometry. Immunohistochemical staining was performed on rheumatoid synovial tissue. Results C1q-immunoassays demonstrated increased levels of IgG (p = 0.01) and IgM (p = 0.0002) ICs in plasma derived from RA patients possessing anti-cyclic citrullinated peptide (CCP+) autoantibodies as compared with healthy controls. About one-half of the anti-CCP+ RA possessed circulating ICs containing fibrinogen (p = 0.0004). Fractionation of whole RA plasma revealed citrullinated fibrinogen in the high molecular weight fractions that contained ICs. Positive correlations were observed between fibrinogen-containing ICs and anti-citrullinated fibrinogen autoantibodies, anti-CCP antibody, rheumatoid factor and certain clinical characteristics. Immunohistochemical staining demonstrated co-localisation of fibrinogen, immunoglobulin and complement component C3 in RA pannus tissue. Mass spectrometry analysis of immune complexes immunoprecipitated from RA pannus tissue lysates demonstrated the presence of citrullinated fibrinogen. Conclusion Circulating ICs containing citrullinated fibrinogen are present in one-half of anti-CCP+ RA patients, and these ICs co-localise with C3 in the rheumatoid synovium suggesting that they contribute to synovitis in a subset of RA patients. PMID:18710572

  3. Cachexia and adiposity in rheumatoid arthritis. Relevance for disease management and clinical outcomes.

    Science.gov (United States)

    Challal, Salima; Minichiello, Emeline; Boissier, Marie-Christophe; Semerano, Luca

    2016-03-01

    Altered body composition is a frequent finding in rheumatoid arthritis and is associated with the two major outcomes of the disease: disability and cardiovascular mortality. It is estimated that up to two thirds of patients may be affected by loss of lean mass, the so-called rheumatoid cachexia. Hence, body weight being equal, the relative amount of lean mass is lower and that of body fat is higher in rheumatoid arthritis patients vs. healthy controls. Both disease-related factors and other factors, like drug treatments, physical activity and nutrition contribute to modify body composition in rheumatoid arthritis. The effect of pharmacological treatments, and notably of anti-TNF drugs, on body composition is controversial. Conversely, training programs to stimulate muscle growth can restore lean mass and reduce adiposity. There is good evidence that amelioration of body composition ameliorates function and reduces disability. Currently, there is no evidence that interventions that modify body composition can reduce cardiovascular morbidity and mortality in rheumatoid arthritis. Copyright © 2015. Published by Elsevier SAS.

  4. Tumor detection using radiolabeled monoclonal antibodies

    International Nuclear Information System (INIS)

    Moldofsky, P.J.; Powe, J.; Hammond, N.D.

    1987-01-01

    Radioisotope conjugated to monoclonal antibody products has been used for imaging tumors targeted by the antibody. As imaging progresses, new sets of procedural and technical questions arise. In this chapter, we discuss several current problems in imaging tumor with radiolabeled monoclonal antibody. These include (1) methods for selection of specific antibody and, once the particular antibody is selected, which fragment form is to be used; (2) imaging procedures: what are the optimum imaging parameters, such as optimum time for imaging after administration of tracer and considerations regarding background subtraction; and (3) noninvasive quantitative techniques: quantitation of localization of antibody indirectly from quantitative information in the images.100 references

  5. Indirect costs of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Filip Raciborski

    2015-12-01

    Full Text Available It is estimated that in Poland about 400,000 persons in general suffer from inflammatory joint diseases, including rheumatoid arthritis (RA. Epidemiological surveys documenting the frequency and disturbance of musculoskeletal disorders in the Polish population are few in number. Most of the estimations are based on epidemiological data from other countries (prevalence of 0.5–1%. According to the data of the National Health Fund in Poland 135,000–157,000 persons in total are treated because of rheumatoid arthritis per year [ICD10 (International Statistical Classification of Diseases and Related Health Problems: M05, M06]. In the case of this group of diseases indirect costs significantly outweigh the direct costs. Indirect costs increase together with activity level of the disease. The cost analysis of productivity loss of RA patients indicates that sickness absenteeism and informal care are the most burdensome. At the national level it amounts in total from 1.2 billion to 2.8 billion PLN per year, depending on the method of analysis. These costs could be significantly reduced through early diagnosis and introduction of effective treatment.

  6. MINERAL WATERS IN RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    BORGES, TIAGO

    2013-02-01

    Full Text Available Background: Rheumatoid arthritis (RA is an autoimmune disorder affecting nearly 1% of adult population. First-line therapies include disease-modifying antirheumatic drugs, but creno-balneotherapyis often prescribed in rheumatic disorders and RA is no exception. Objectives: To know the efficacy of creno-balneotherapy in RA. Methods: A Medline based search was made using MeSH terms “balneology” and “rheumatoid arthritis”. Articles concerning the use of mineral waters in RA treatment were included. Results: In RA, two traditional ways of employing mineral waters are commonly used: immersion and peliotherapy. Each owns their benefits to non-specific or hydrotherapeutic effects and specific or crenotherapeutic effects. Mineral waters must be regarded as an adjuvant therapy in quiescent, stable or non-progressive RA. Significant benefits have been accomplished with radonenriched and sulphurous waters. Isothermal or hyperthermal waters should be preferred. Conclusions: Although there is a global lack of evidence, mineral waters are a safe and effective therapy to be considered in RA.

  7. Generation of a Monoclonal Antibody against Mycoplasma spp. following Accidental Contamination during Production of a Monoclonal Antibody against Lawsonia intracellularis

    OpenAIRE

    Hwang, Jeong-Min; Lee, Ji-Hye; Yeh, Jung-Yong

    2012-01-01

    This report describes Mycoplasma contamination of Lawsonia intracellularis cultures that led to the unintended acquisition of a monoclonal antibody against Mycoplasma spp. during the attempted generation of a monoclonal antibody against L. intracellularis.

  8. [Rheumatoid arthritis as a connective tissue disease].

    Science.gov (United States)

    Targońska-Stępniak, Bożena

    2018-01-01

    The available data indicate that seropositive rheumatoid arthritis (RA) develops as a result of systemic, autoimmune reaction directed against a range of "self" peptides/proteins that have undergone specific forms of post-translational modification. The development and progress of autoimmunity may be triggered by non-specific, local inflammatory processes outside the joints, for example in the oral or respiratory mucous membrane. The disease occurs in genetically susceptible individuals under the influence of environmental risk factors that promote autoimmunity and consequently the inflammatory process. Smoking is particularly linked with RA pathogenesis. Synovitis of multiple, symmetrical, peripheral joints is the most typical feature of RA which results in irreversible damage to joints structure and as a consequence in disability of patients. However, the inflammatory process in the course of RA has a systemic, constitutional nature. Therefore, extra-articular symptoms with internal organ involvement may occur additionally to synovitis, what is an unfavorable prognostic factor. Extra-articular manifestations of RA are associated with the high disease activity both inflammatory and immunological. They occur in patients with severe form of the disease and contribute to a significant lifespan reduction. This is usually associated with progressive atherosclerosis and cardiovascular complications. The systemic inhibition of an abnormal immune system activity is the mainstay of the effective RA treatment. The currently used disease modifying antirheumatic drugs affect the activity and function of different constituents of the immune system, including B and T lymphocytes and the main pro-inflammatory cytokines, and contribute to autoimmune and inflammatory processes.

  9. LIPOPOLYSACCHARIDE INDUCES THE PRODUCTION OF DIAGNOSTIC MONOCLONAL ANTIBODY BY HYBRIDOMA CELLS AGAINST CONGENITAL ADRENAL HYPERPLASIA

    Directory of Open Access Journals (Sweden)

    GEK KEE CHUA

    2017-11-01

    Full Text Available The purpose of this research is to screen and identify the potential inducers in maximizing the production of monoclonal antibody by hybridoma 192 cell line for Congenital Adrenal Hyperplasia diagnostic. There are nine inducers used in this research, namely lysozyme, aldolase, sodium butyrate, sodium phosphate, potassium phosphate, dimethyl sulfoxide, lipopolysaccharide, essential amino acids, and nonessential amino acids. Hybridoma 192 cell was cultured in 5% CO2 incubator at 37°C and ˃80% humidity in the medium with different concentrations of inducer agents. The inducers were added at the beginning of the culture and the samples were taken after 72 h of culture. The performance of these inducer agents was assessed based on the maximum monoclonal antibody titer achieved using Enzyme-linked Immunosorbent Assay. Lipopolysaccharide was found to increase the maximum monoclonal antibody titer when supplemented at 8 to 12 µg/mL. After optimization using one-factor central composite design at this range, the optimum point was determined to be 8 µg/mL. Verification experiments shows that lipopolysaccharide enhanced the average specific monoclonal antibody production rate by 56% relative to control. In conclusion, lipopolysaccharide at 8 µg/mL is able to increase the monoclonal antibody specific production of hybridoma 192 cell line.

  10. Management of Patients With Hepatitis C Virus, Monoclonal Gammopathy of Undetermined Significance, and Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Alisse Hannaford BS

    2017-04-01

    Full Text Available Background and Aim: The vast majority of the 2.7 million individuals in the United States who are currently infected with hepatitis C virus (HCV were born between 1945 and 1965. The median age of these patients in this particular generation at the time of this writing was 55 years. In the general population, older age is a risk factor for multiple myeloma (MM and other monogammopathies. As the baby boomer population ages, HCV providers are increasingly likely to encounter HCV-infected patients with a monoclonal gammopathy. Guidelines for managing these patients are needed. Methods: We conducted a detailed case series investigation of 4 HCV-positive patients with MM or a monoclonal gammopathy disorder. Patients were followed at the Mount Sinai Faculty Practice liver clinic. We also performed a detailed review of the literature exploring if there is any known association between HCV, MM, and monoclonal gammopathy. Results and Conclusions: There is no convincing evidence of a causal association between HCV and MM. HCV is linked to type II and type III cryoglobulinemia, specific kinds of monoclonal gammopathies of determinable significance. Whether a link exists between HCV and MM or monoclonal gammopathy of undetermined significance is unclear. Our case series provides the first evidence that modern HCV treatments with direct-acting antivirals can be safely and effectively co-administered with MM chemotherapy.

  11. Strain differentiation of polioviruses with monoclonal antibodies.

    NARCIS (Netherlands)

    A.D.M.E. Osterhaus (Albert); A.L. van Wezel; A.J.H. Stegmann; J.A.A.M. van Asten (Jack)

    1984-01-01

    textabstractPanels of monoclonal antibodies raised against different poliovirus type 1, 2 and 3 strains, were tested in a micro-neutralization test and in a micro-enzyme linked immunosorbent assay against a large number of poliovirus strains. The results were compared with those obtained with the

  12. Monoclonal antibodies reactive with hairy cell leukemia

    NARCIS (Netherlands)

    Visser, L; Shaw, A; Slupsky, J; Vos, H; Poppema, S

    Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia.

  13. Monoclonal antibody technologies and rapid detection assays

    Science.gov (United States)

    Novel methodologies and screening strategies will be outlined on the use of hybridoma technology for the selection of antigen specific monoclonal antibodies. The development of immunoassays used for diagnostic detection of prions and bacterial toxins will be discussed and examples provided demonstr...

  14. Monoclonal antibody therapy of inflammatory bowel disease

    NARCIS (Netherlands)

    van Deventer, S. J.; Camoglio, L.

    1996-01-01

    Several anti-inflammatory drugs have therapeutic efficacy in inflammatory bowel disease, but their targets remain incompletely characterized. The development of monoclonal antibodies that either recognize epitopes on immune-competent cells, or neutralize pro-inflammatory cytokines, has helped to

  15. Monoclonal Antibody Therapy for Advanced Neuroblastoma

    Science.gov (United States)

    NCI is sponsoring two clinical trials of a monoclonal antibody called ch14.18, in combination with other drugs, to see if the antibody may be helpful for children or young adults (up to age 21) with relapsed or refractory neuroblastoma.

  16. Rheumatoid Arthritis and Complementary Medicine: In Depth

    Science.gov (United States)

    ... unproven. Many factors—including differences in tai chi styles, number of movements, length of the practice, and ... JY, Kim YJ, et al. Acupuncture for symptom management of rheumatoid arthritis: a pilot study. Clinical Rheumatology. ...

  17. Balneotherapy (or spa therapy) for rheumatoid arthritis

    NARCIS (Netherlands)

    Verhagen, A.P.; Bierma-Zeinstra, S.M.A.; Boers, M.; Cardoso, J.R.; Lambeck, J.; de Bie, R.; de Vet, H.C.W.

    2015-01-01

    BACKGROUND: No cure for rheumatoid arthritis (RA) is known at present, so treatment often focuses on management of symptoms such as pain, stiffness and mobility. Treatment options include pharmacological interventions, physical therapy treatments and balneotherapy. Balneotherapy is defined as

  18. Tracheomegaly in association with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Celenk, C.; Selcuk, M.B.; Oezyazici, B.; Celenk, P.; Kuru, Oe.

    2000-01-01

    Herein we present a case of tracheomegaly seen in a patient with rheumatoid arthritis. To the authors' knowledge, and from a review of the literature, this combination has not been previously described. (orig.)

  19. Rheumatoid Arthritis | Ally | South African Family Practice

    African Journals Online (AJOL)

    Immune-mediated inflammatory disorders include a clinically diverse group of conditions sharing similar pathogenic mechanisms. Conditions such as rheumatoid arthritis, psoriasis, spondyloarthropathy, inflammatory bowel disease and connective tissue diseases are characterised by immune dysregulation and chronic ...

  20. Large-scale linkage analysis of 1302 affected relative pairs with rheumatoid arthritis

    Science.gov (United States)

    Hamshere, Marian L; Segurado, Ricardo; Moskvina, Valentina; Nikolov, Ivan; Glaser, Beate; Holmans, Peter A

    2007-01-01

    Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p << 0.001) and rheumatoid factor (RF) IgM (p << 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates. PMID:18466440

  1. Comparative study between immunoturbidimetric and latex agglutination methods for the detection of rheumatoid factor Estudo comparativo entre as técnicas de aglutinação em látex e de imunoturbidimetria para a detecção de fator reumatoide

    Directory of Open Access Journals (Sweden)

    Katya Cristina Rocha

    2013-02-01

    Full Text Available INTRODUCTION: The rheumatoid factor (RF is the most common antibody found in patients with rheumatoid arthritis. It is an inflammatory chronic disease characterized by articular involvement, inflammation of synovial fluid, tissue infiltration by leucocytes and joint destruction, which ultimately determine articular deformities. The rheumatoid factor is found in 70%-80% of the adult population and in 10% of the young population. OBJECTIVE: The aim of this research was to compare immunoturbidimetric and latex agglutination methods for the detection of RF in serum. RESULTS: The immunoturbidimetric method displayed sensitivity (95.2%, specificity (89.4% and high positive correlation (R² = 0,8077 with the latex agglutination method in positive serum samples. CONCLUSION: The study allowed to demonstrate that both immunoturbidimetric and latex agglutination methods equally discriminate between negative and positive serum samples for RF.INTRODUÇÃO: O fator reumatoide (FR é o autoanticorpo mais comum encontrado em pacientes com artrite reumatoide, uma doença crônica inflamatória caracterizada pelo envolvimento articular com inflamação do líquido sinovial, infiltração de tecido por leucócitos e destruição das articulações, que acaba por determinar deformidades articulares. O FR é encontrado em 70%-80% da população adulta e em 10% da população juvenil. OBJETIVO: Comparar os métodos de imunoturbidimetria e aglutinação (prova do látex para a determinação de FR em soro. RESULTADO: Foi possível observar que o método imunoturbidimétrico apresenta sensibilidade (95,2%, especificidade (89,4% e correlação positiva elevada (R² = 0,8077 com o método de aglutinação pelo látex em amostras de soro positivas. CONCLUSÃO: O estudo permitiu demonstrar que o método imunoturbidimétrico e o método de aglutinação pelo látex são igualmente capazes de discriminar amostras negativas e positivas para FR.

  2. Comparative tumour localization properties of radiolabelled monoclonal antibody preparations of defined immunoreactivities

    International Nuclear Information System (INIS)

    Pimm, M.V.; Baldwin, R.W.

    1987-01-01

    The immunoreactive fraction of an anti-CEA monoclonal antibody preparation has been progressively decreased by the addition of increasing proportions of impurity in the form of immunologically inert mouse immunoglobulin. Following radioiodination, the immunoreactive fractions of the preparations were determined and their localization in a human tumour xenograft in nude mice was assessed. There was a progressive decline in tumour localization, from tumour to blood ratios of 2:1 with unadulterated antibody to 0.6:1 with preparations only 15% with respect to the initial antibody. These findings demonstrate that the immunoreactive fraction of monoclonal antibody preparations is a major limiting factor in tumour localization and this has implications for experimental and clinical applications of monoclonal antibodies. (orig.)

  3. Molecular mechanism for the action of the anti-CD44 monoclonal antibody MEM-85

    Czech Academy of Sciences Publication Activity Database

    Škerlová, Jana; Král, Vlastimil; Kachala, M.; Fábry, Milan; Bumba, Ladislav; Svergun, D.I.; Tosner, Z.; Veverka, V.; Řezáčová, Pavlína

    2015-01-01

    Roč. 191, č. 2 (2015), s. 214-223 ISSN 1047-8477 R&D Projects: GA ČR(CZ) GA15-11851S EU Projects: European Commission 264257 Institutional support: RVO:68378050 ; RVO:61388971 Keywords : CD44 * Epitope mapping * Monoclonal antibody * MEM-85 * SAXS * NMR Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.570, year: 2015

  4. Molecular mechanism for the action of the anti-CD44 monoclonal antibody MEM-85

    Czech Academy of Sciences Publication Activity Database

    Škerlová, Jana; Král, V.; Kachala, M.; Fábry, M.; Bumba, L.; Svergun, D. I.; Tošner, Z.; Veverka, Václav; Řezáčová, Pavlína

    2015-01-01

    Roč. 191, č. 2 (2015), s. 214-223 ISSN 1047-8477 R&D Projects: GA MŠk(CZ) LK11205; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : CD44 * epitope mapping * monoclonal antibody * MEM-85 * NMR * SAXS Subject RIV: CE - Biochemistry Impact factor: 2.570, year: 2015

  5. Monoclonal antibody FsC-47 against carp sperm creatine kinase

    Czech Academy of Sciences Publication Activity Database

    Koubek, Pavel; Elzeinová, Fatima; Šulc, Miroslav; Linhart, O.; Pěknicová, Jana

    2006-01-01

    Roč. 25, č. 3 (2006), s. 154-157 ISSN 1554-0014 R&D Projects: GA ČR(CZ) GA524/03/0178 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50200510 Keywords : creatin kinase * monoclonal antibody * carp sperm Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.411, year: 2006

  6. Agonistic Human Monoclonal Antibodies against Death Receptor 4 (DR4) | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute is seeking parties interested in licensing human monoclonal antibodies (mAbs) that bind to death receptor 4 ("DR4"). The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and its functional receptors, DR4 and DR5, have been recognized as promising targets for cancer treatment.

  7. Application of monoclonal antibodies against trophoblastic cells to study female infertility

    Czech Academy of Sciences Publication Activity Database

    Sedláková, Alena; Elzeinová, Fatima; Bukovský, A.; Madar, J.; Ulčová-Gallová, Z.; Pěknicová, Jana

    2004-01-01

    Roč. 51, č. 6 (2004), s. 482-483 ISSN 1046-7408. [European congress of reproductive immunology. Plzeň, 30.06.2004-03.07.2004] R&D Projects: GA MŠk LN00B030 Keywords : trophoblast * monoclonal antibody * ELISA Subject RIV: EC - Immunology Impact factor: 1.808, year: 2004

  8. Application physiotherapy in rehabilitation rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Angela Nogas

    2017-02-01

    National University of Water and Environmental Engineering   Abstract Background: Rheumatoid arthritis is one of the most common forms of inflammatory diseases of the joints. The disease leads to deformation, then to destruction of the diseased joint and to disability. Physiotherapy is used for the treatment and rehabilitation of rheumatoid arthritis. It is assumed that physiotherapy treatments that promote remission of the disease, improve the quality of patients’ life, create the necessary conditions for comprehensive rehabilitation programs. Objective: Systematic’s review conducting of studies that assess the effect of physiotherapy in the rehabilitation of patients with rheumatoid arthritis. Methods: Theoretical analysis of scientific and methodical literature, methods of analysis, synthesis, generalization. Results: To reduce inflammation in the joints is performed UV of affected joints weak or medium erythermal or middle erythermal doses used UHF therapy. UHF-therapy prescribed to the area of joint in I or II dose, duration 10 min., the course – 5-8 treatments. For patients with minimal activity is added electrophoresis NSAIDs. Electrophoresis aspirin is applied on the affected joints (every day, the course – 10-12 procedures, which favorably affect the course of rheumatoid arthritis. Conclusions: Physical therapy can reduce pain and stiffness in the joints, prevent deformity and restore function, improve independence and quality of life. State of the art is a major incentive to develop new activities in the treatment and rehabilitation of patients with rheumatoid arthritis to improve joint functional activity and their physical health.   Keywords: rheumatoid arthritis, physiotherapy, rehabilitation, hydrotherapy.

  9. An unusual cause of pain post ankle arthrodesis in patients with rheumatoid arthritis.

    LENUS (Irish Health Repository)

    Burke, Neil G

    2012-02-01

    Rheumatoid arthritis is an autoimmune disease which frequently affects the ankle and foot. End stage ankle arthritis from rheumatic disease is commonly managed by the established practice of ankle arthrodesis. Among the adverse sequelae causing pain following this surgery is infection, pseudo-arthrosis and non-union. Stress fracture of the distal third is a recognised but unusual cause of pain of tibia following ankle arthrodesis. The authors\\' present three patients with rheumatoid arthritis who sustained a stress fracture of the distal tibia following arthrodesis, and discuss the contributing factors and highlight the need for orthopaedic surgeons to be suspicious of this complication post surgery.

  10. Radiographic progression of rheumatoid arthritis related to some clinical and laboratory parameters

    International Nuclear Information System (INIS)

    Carvalho, A. de; Graudal, H.

    1980-01-01

    In 188 patients followed for 3 to 12 years, the radiologic course of rheumatoid arthritis was assessed in 20 joint groups. A severe course in most joints was related to the presence of rheumatoid factor and to high values of the ESR. Granulocyte-specific antinuclear antibodies were related to a severe course in most joints. The presence of nodules, the Rose-Waaler titre and the presence of organ non-specific antinuclear antibodies were generally unrelated to the course of the disease. (Auth.)

  11. A Case of Disseminated Histoplasmosis in a Patient with Rheumatoid Arthritis on Abatacept.

    Science.gov (United States)

    Jain, Nina; Doyon, Jeffrey B; Lazarus, Jacob E; Schaefer, Inga-Marie; Johncilla, Melanie E; Agoston, Agoston T; Dalal, Anuj K; Velásquez, Gustavo E

    2018-05-01

    Biologic agents are effective treatments for rheumatoid arthritis but are associated with important risks, including severe infections. Tumor Necrosis Factor (TNF) α inhibitors are known to increase the risk of systemic fungal infections such as disseminated histoplasmosis. Abatacept is a biologic agent with a mechanism different from that of TNFα inhibitors: It suppresses cellular immunity by competing for the costimulatory signal on antigen-presenting cells. The risk of disseminated histoplasmosis for patients on abatacept is not known. We report a case of abatacept-associated disseminated histoplasmosis and review the known infectious complications of abatacept. While the safety of resuming biologic agents following treatment for disseminated histoplasmosis is also not known, abatacept is recommended over TNFα inhibitors for rheumatoid arthritis patients with a prior serious infection. We discuss the evidence supporting this recommendation and discuss alternative treatments for rheumatoid arthritis patients with a history of a serious infection.

  12. Rheumatoid arthritis affecting temporomandibular joint

    Directory of Open Access Journals (Sweden)

    Amandeep Sodhi

    2015-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic, systemic, autoimmune inflammatory disorder that is characterized by joint inflammation, erosive properties and symmetric multiple joint involvement. Temporomandibular joint (TMJ is very rare to be affected in the early phase of the disease, thus posing diagnostic challenges for the dentist. Conventional radiographs fail to show the early lesions due to its limitations. More recently cone-beam computed tomography (CBCT has been found to diagnose the early degenerative changes of TMJ and hence aid in the diagnosis of the lesions more accurately. Our case highlights the involvement of TMJ in RA and the role of advanced imaging (CBCT in diagnosing the bony changes in the early phase of the disease.

  13. Radiological manifestations of rheumatoid arthritis

    International Nuclear Information System (INIS)

    Kapp, H.J.

    1997-01-01

    Rheumatoid arthritis preferrably becomes manifest at the synovial joints of the limbs, especially at the small joints of the hands and feet, at bursae and synovial sheathes. The pathologic lesions are less frequently found at cartilaginous joints or entheses. The lesions very often are symmetrically distributed and are characterized by the following: 1. A periarticular, spindle-shaped opacity with a density similar to soft-tissue, induced by an inflammatory hypertrophy of the synovia, a serosynovitis, or an edematous impregnation of the periarticular tissue. 2. A juxta-articular osteoporosis, most probably caused by a neighbouring synovialitis accompanied by hyperemia. 3. A diffuse joint cavity narrowing due to a destruction of the articular cartilage by the pannus, a fibrovascular resorptive tissue. 4. Central as well as marginal erosions, caused by destruction of ossous material by the pannus. 5. Subchondral signal cysts, likewise unduced by the pannus. (Orig./AJ) [de

  14. Pharmacotherapy Options in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Pradeep Kumar

    2013-01-01

    Full Text Available Drugs form the mainstay of therapy in rheumatoid arthritis (RA. Five main classes of drugs are currently used: analgesics, non-steroidal anti-inflammatories (NSAIDs, glucocorticoids, nonbiologic and biologic disease-modifying antirheumatic drugs. Current clinical practice guidelines recommend that clinicians start biologic agents if patients have suboptimal response or intolerant to one or two traditional disease modifying agents (DMARDs. Methotrexate, sulfasalazine, leflunomide and hydroxychloroquine are the commonly used DMARDs. Currently, anti-TNF is the commonly used first line biologic worldwide followed by abatacept and it is usually combined with MTX. There is some evidence that tocilizumab is the most effective biologic as a monotherapy agent. Rituximab is generally not used as a first line biologic therapy due to safety issues but still as effective as anti-TNF. The long term data for the newer oral small molecule biologics such as tofacitinib is not available and hence used only as a last resort.

  15. Rheumatoid arthritis in Saudi Arabia

    Science.gov (United States)

    Almoallim, Hani M.; Alharbi, Laila A.

    2014-01-01

    The status of rheumatoid arthritis (RA) in Saudi Arabia (SA) was examined from various perspectives based on a systematic literature review and the authors’ personal experiences. In this regard, database and journal search were conducted to identify studies on RA in SA, yielding a total of 43 articles. Although efforts have been made to promote RA research in SA, current studies mostly represent only a few centers and may not accurately portray the national status of RA care. Notably, biological therapies were introduced early for almost all practicing rheumatologists in SA (government and private). However, no national guidelines regarding the management of RA have been developed based on local needs and regulations. Also, while efforts were made to establish RA data registries, they have not been successful. Taken together, this analysis can contribute to the planning of future guidelines and directives for RA care in SA. PMID:25491208

  16. Kidney involvement in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    P. Lazzarini

    2011-09-01

    Full Text Available Rheumatoid Arthritis (RA is a widespread disease and its renal involvement, relatively common, is clinically significant because worsens course and mortality of the primary disease. There is still no agreement on the prevalence of renal disorders in RA: data analysis originates from different sources, as death certificates, autopsies, clinical and laboratory findings and kidney biopsies, each with its limitations. Histoimmunological studies on bioptical specimens of patients with RA and kidney damage, led to clarify prevalent pathologies. In order of frequency: glomerulonephritis and amyloidosis (60-65% and 20-30% respectively, followed by acute or chronic interstitial nephritis. Kidney injury during RA includes secondary renal amyloidosis, nephrotoxic effects of antirheumatic drugs and nephropathies as extra-articular manifestations (rheumatoid nephropathy. Amyloidosis affects survival, increases morbidity and is the main cause of end stage renal disease in patients with RA and nephropathy. Strong association between RA activity and amyloidosis needs the use of immunosuppressive and combined therapies, to prevent this complication and reduce risk of dialysis. Long-lasting and combined RA pharmacotherapy involves various renal side effects. In this review we describe NSAIDs and DMARDs (Disease-Modifying Antirheumatic Drugs nephrotoxicity, particularly by gold compounds, D-penicillamine, cyclosporine A and methotrexate. Rare cases of IgA glomerulonephritis during immunomodulating therapy with leflunomide and TNF blocking receptor (etanercept are reported; real clinical significance of this drug-related nephropathy will be established by development of RA treatment. In RA nephropathies, mesangial glomerulonephritis is the most frequent histological lesion (35-60 % out of biopsies from patients with urinary abnormalities and/or kidney impairment, followed by minimal change glomerulopathy (3-14% and p-ANCA positive necrotizing crescentic

  17. Cuban Monoclonal Antibodies for Radioimmunodiagnosis and Radioimmunotherapy of Cancer Diseases

    International Nuclear Information System (INIS)

    Casaco, A.

    2009-01-01

    The Centre of Molecular Immunology produces monoclonal antibodies for treating cancer diseases. We are mainly focus on two target systems; one is the epidermal growth factor receptor (EGF-R) because there is a tremendous relationship between the EGF/EGF-R system and several human tumours such as lung, head and neck, ovarian breast and brain cancers; the second one is the ganglioside system, the relevance of certain gangliosides in tumour growth and metastatic dissemination has been well documented, GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues. Nimotuzumab (h-R3) is a humanized monoclonal antibody (mAb) that was obtained by complementarity-determining regions grafting of a murine mAb (ior egf/r3) to a human framework having remarkable antiproliferative, pro-apoptotic, and antiangiogenic effects. A Phase I clinical trial was performed to evaluate the toxicity and clinical effect of an intracavitary (intracerebral) administration of a single dose of nimotuzumab (h-R3) labelled with increasing doses of 188Re. All patients bearing astrocytomas grade III/IV should be treated previously with conventional therapies and have an EGF-R overexpression in the tumour, demonstrated by immunohistochemical study. Maximal tolerated dose was 3 mg of the h-R3 labelled with 10 mCi of 188 Re. The radioimmunoconjugate showed a high retention in the surgical created resection cavity and the brain adjacent tissues with a mean value of 85.5% of the injected dose one hour post-administration. This radioimmunoconjugate may be relatively safe and a promising therapeutic approach for treating high grade gliomas. GM3(NeuGc) ganglioside is particularly interesting due to its restrictive expression in normal human tissues according to immunohistochemical studies, using either polyclonal or monoclonal antibodies. But both immunohistochemical and biochemical methods have strongly suggested its over-expression in human breast and colon

  18. Generation mechanism of RANKL(+) effector memory B cells: relevance to the pathogenesis of rheumatoid arthritis.

    Science.gov (United States)

    Ota, Yuri; Niiro, Hiroaki; Ota, Shun-Ichiro; Ueki, Naoko; Tsuzuki, Hirofumi; Nakayama, Tsuyoshi; Mishima, Koji; Higashioka, Kazuhiko; Jabbarzadeh-Tabrizi, Siamak; Mitoma, Hiroki; Akahoshi, Mitsuteru; Arinobu, Yojiro; Kukita, Akiko; Yamada, Hisakata; Tsukamoto, Hiroshi; Akashi, Koichi

    2016-03-16

    The efficacy of B cell-depleting therapies for rheumatoid arthritis underscores antibody-independent functions of effector B cells such as cognate T-B interactions and production of pro-inflammatory cytokines. Receptor activator of nuclear factor κB ligand (RANKL) is a key cytokine involved in bone destruction and is highly expressed in synovial fluid B cells in patients with rheumatoid arthritis. In this study we sought to clarify the generation mechanism of RANKL(+) effector B cells and their impacts on osteoclast differentiation. Peripheral blood and synovial fluid B cells from healthy controls and patients with rheumatoid arthritis were isolated using cell sorter. mRNA expression of RANKL, osteoprotegerin, tumor necrosis factor (TNF)-α, and Blimp-1 was analyzed by quantitative real-time polymerase chain reaction. Levels of RANKL, CD80, CD86, and CXCR3 were analyzed using flow cytometry. Functional analysis of osteoclastogenesis was carried out in the co-culture system using macrophage RAW264 reporter cells. RANKL expression was accentuated in CD80(+)CD86(+) B cells, a highly activated B-cell subset more abundantly observed in patients with rheumatoid arthritis. Upon activation via B-cell receptor and CD40, switched-memory B cells predominantly expressed RANKL, which was further augmented by interferon-γ (IFN-γ) but suppressed by interleukin-21. Strikingly, IFN-γ also enhanced TNF-α expression, while it strongly suppressed osteoprotegerin expression in B cells. IFN-γ increased the generation of CXCR3(+)RANKL(+) effector B cells, mimicking the synovial B cell phenotype in patients with rheumatoid arthritis. Finally, RANKL(+) effector B cells in concert with TNF-α facilitated osteoclast differentiation in vitro. Our current findings have shed light on the generation mechanism of pathogenic RANKL(+) effector B cells that would be an ideal therapeutic target for rheumatoid arthritis in the future.

  19. Randomised controlled trial of tumour necrosis factor inhibitors against combination intensive therapy with conventional disease-modifying antirheumatic drugs in established rheumatoid arthritis: the TACIT trial and associated systematic reviews.

    Science.gov (United States)

    Scott, David L; Ibrahim, Fowzia; Farewell, Vern; O'Keeffe, Aidan G; Ma, Margaret; Walker, David; Heslin, Margaret; Patel, Anita; Kingsley, Gabrielle

    2014-10-01

    Rheumatoid arthritis (RA) is initially treated with methotrexate and other disease-modifying antirheumatic drugs (DMARDs). Active RA patients who fail such treatments can receive tumour necrosis factor inhibitors (TNFis), which are effective but expensive. We assessed whether or not combination DMARDs (cDMARDs) give equivalent clinical benefits at lower costs in RA patients eligible for TNFis. An open-label, 12-month, pragmatic, randomised, multicentre, two-arm trial [Tumour necrosis factor inhibitors Against Combination Intensive Therapy (TACIT)] compared these treatment strategies. We then systematically reviewed all comparable published trials. The TACIT trial involved 24 English rheumatology clinics. Active RA patients eligible for TNFis. The TACIT trial compared cDMARDs with TNFis plus methotrexate or another DMARD; 6-month non-responders received (a) TNFis if in the cDMARD group; and (b) a second TNFi if in the TNFi group. The Heath Assessment Questionnaire (HAQ) was the primary outcome measure. The European Quality of Life-5 Dimensions (EQ-5D), joint damage, Disease Activity Score for 28 Joints (DAS28), withdrawals and adverse effects were secondary outcome measures. Economic evaluation linked costs, HAQ changes and quality-adjusted life-years (QALYs). In total, 432 patients were screened; 104 started on cDMARDs and 101 started on TNFis. The initial demographic and disease assessments were similar between the groups. In total, 16 patients were lost to follow-up (nine in the cDMARD group, seven in the TNFi group) and 42 discontinued their intervention but were followed up (23 in the cDMARD group and 19 in the TNFi group). Intention-to-treat analysis with multiple imputation methods used for missing data showed greater 12-month HAQ score reductions with initial cDMARDs than with initial TNFis [adjusted linear regression coefficient 0.15, 95% confidence interval (CI) -0.003 to 0.31; p = 0.046]. Increases in 12-month EQ-5D scores were greater with initial c

  20. Goal-setting in multidisciplinary team care for patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Meesters, Jorit; Hagel, Sofia; Klokkerud, Mari

    2013-01-01

    %) to "Environmental Factors" (e-codes). Thirty-five of the 151 unique ICF codes (23%) were not in the comprehensive ICF Core Set for RA, whereas 23 of the ICF codes in this Core Set (24%) were not in the rehabilitation goals. Conclusion: The goals set in a team rehabilitation setting for patients with rheumatoid...

  1. Productivity at work and quality of life in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    van Vilsteren, Myrthe; Boot, Cecile R. L.; Knol, Dirk L.; van Schaardenburg, Dirkjan; Voskuyl, Alexandre E.; Steenbeek, Romy; Anema, Johannes R.

    2015-01-01

    The aim of this study was to determine which combination of personal, disease-related and environmental factors is best associated with at-work productivity loss in patients with rheumatoid arthritis (RA), and to determine whether at-work productivity loss is associated with the quality of life for

  2. Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis

    DEFF Research Database (Denmark)

    Pedersen, Line Merete Blak; Jacobsen, Søren; Garred, Peter

    2007-01-01

    To study the role of shared epitope (SE) susceptibility genes, alone and in combination with tobacco smoking and other environmental risk factors, for risk of subtypes of rheumatoid arthritis (RA) defined by the presence or absence of serum antibodies against cyclic citrullinated peptides (CCPs)....

  3. Compliance in rheumatoid arthritis and the role of formal patient education

    NARCIS (Netherlands)

    Brus, H.L.M.; Brus, Herman; van de Laar, Mart A F J; Taal, Erik; Rasker, Johannes J.; Wiegman, O.

    1997-01-01

    Objective: This study was performed to determine the compliance with the basic treatments for rheumatoid arthritis (RA; medication, physical therapy, and ergonomic measures), to study psychological factors that influence compliance in light of the social learning theory, to learn whether patient

  4. Targeting the Fas/FasL system in Rheumatoid Arthritis therapy: Promising or risky?

    NARCIS (Netherlands)

    Calmon-Hamaty, Flavia; Audo, Rachel; Combe, Bernard; Morel, Jacques; Hahne, Michael

    2015-01-01

    Rheumatoid Arthritis (RA) is a chronic inflammatory disease affecting synovial joints. Tumor necrosis factor (TNF) α is a key component of RA pathogenesis and blocking this cytokine is the most common strategy to treat the disease. Though TNFα blockers are very efficient, one third of the RA

  5. Productivity at work and quality of life in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Vilsteren, M. van; Boot, C.R.; Knol, D.L.; Schaardenburg, D. van; Voskuyl, A.E.; Steenbeek, R.; Anema, J.R.

    2015-01-01

    Background The aim of this study was to determine which combination of personal, disease-related and environmental factors is best associated with at-work productivity loss in patients with rheumatoid arthritis (RA), and to determine whether at-work productivity loss is associated with the quality

  6. Gene therapy works in animal models of rheumatoid arthritis...so what!

    NARCIS (Netherlands)

    Loo, F.A.J. van de; Geurts, J.; Berg, W.B. van den

    2006-01-01

    Rheumatoid arthritis (RA) is a systemic disease with polyarticular manifestation of chronic inflammation in the knees and small joints of hand and feet. The current systemic anti-tumor necrosis factor (TNF)-alpha therapies with biologics ameliorate disease in 60% to 70% of RA patients. However,

  7. RITUXIMAB: NEW POTENTIALITIES OF THERAPY FOR RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    D E Karateev

    2008-01-01

    Full Text Available Some patients with rheumatoid arthritis (RA are unresponsive or intolerant to both synthetic first-line anti-inflammatory drugs (FLAID and tumor necrosis factor (TNF а inhibitors already included into all the treatment standards . Along with the conventional methods for overcoming drug resistance - switching to another FLAID or another TNF а blocker, the use of biologicals with another mechanism of action rather than suppression of TNF а gives a good account of itself. Prominent among these agents is the anti-B-cell drug rituximab. The new possibilities of the therapy, which open up the use of rituximab in patients with RA, are discussed.

  8. Cigarette smoking and pulmonary diffusion defects in rheumatoid arthritis.

    Science.gov (United States)

    Westedt, M L; Hazes, J M; Breedveld, F C; Sterk, P J; Dijkman, J H

    1998-01-01

    The pathogenesis of lung disease in rheumatoid arthritis (RA) has still to be defined. Risk factors associated with lung involvement in RA were investigated by means of pulmonary function studies in 40 RA patients without apparent lung disease. A decreased carbon monoxide (CO) diffusion capacity indicative of interstitial lung disease (ILD) was the main pulmonary function defect found in the first 20 patients. The occurrence was associated with current cigarette smoking. This association was confirmed in a case control study performed subsequently. These data suggest that ILD in RA is stimulated by smoking and provide an additional argument that modification of smoking behaviour in RA patients might lead to less severe complications.

  9. Newborn infant characteristics and risk of future rheumatoid arthritis

    DEFF Research Database (Denmark)

    Svendsen, Anders J; Kyvik, Kirsten O; Houen, Gunnar

    2014-01-01

    Low birth weight has been proposed as a risk factor for rheumatoid arthritis (RA). The twin-control study design provides an opportunity to investigate the significance of potential prenatal determinants for adult morbidity by accounting for maternal characteristics and early environmental...... for developing RA as first born twin was 2.33 (95 % CI 0.97-5.60) when adjusting for birth length, birth weight, and sex, irrespective of ACPA status. In this twin-control study, birth weight was not associated with the development of RA in adult life. Being born first may predispose to RA....

  10. Immunogenicity of anti-tumor necrosis factor antibodies-toward improved methods of anti-antibody measurement.

    Science.gov (United States)

    Aarden, Lucien; Ruuls, Sigrid R; Wolbink, Gertjan

    2008-08-01

    To date, millions of people have been treated with therapeutic monoclonal antibodies (TmAbs) for various indications. It is becoming increasingly clear that TmAbs can be immunogenic, which may reduce efficacy or induce adverse effects. Over the years, the importance of antibody formation has been questioned and sometimes minimized, as few antibody responses to TmAbs (HACA or HAHA) were reported. However, the methods to detect and quantify such antibodies used in the past have been problematic. Only recently, methods have been developed that have adequate sensitivity and are not seriously disturbed by false-positive reactions caused by rheumatoid factors, natural antibodies to Fab or F(ab')2 fragments, or Fc interactions of IgG4. The large number of treated patients, in combination with these new assays, presents a unique opportunity to study the anti-antibody immune response in man, possibly allowing us to manipulate immunogenicity in the future.

  11. Epstein-Barr virus and rheumatoid arthritis.

    Science.gov (United States)

    Balandraud, Nathalie; Roudier, Jean

    2018-03-01

    Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, with a 0.5% worldwide prevalence. The cause of RA remains unknown, however both genetic and environmental factors may contribute to its development. Among these is the Epstein-Barr virus (EBV). Here, we discuss several aspects of the close relationship between EBV and RA. Patients with RA have impaired control of EBV infection. Indeed, they have high titres of antibodies against EBV antigens. Their peripheral blood T lymphocytes are less efficient at controlling the outgrowth of EBV-infected B cells. RA patients have more EBV-infected B cells than normal controls, leading to a 10-fold systemic EBV overload. Post-transplant lymphoproliferative disorder (PTLPD) is a polyclonal EBV-positive B lymphocyte proliferation, which can evolve into an EBV-positive B cell lymphoma. RA patients also have an increased risk of developing EBV-associated lymphoproliferative disorder (LPD). Hence the need to monitor EBV load when treating RA patients with immunosuppressors. EBV, a widespread virus, highly recognized by antibodies but never eliminated, is an ideal candidate to trigger chronic immune complex disease. Anti-EBV antibody responses should be considered as one of the chronic autoantibody responses linked to the development of RA, in the same way as anti-citrullinated protein antibodies. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  12. Genetics and epigenetics of rheumatoid arthritis

    Science.gov (United States)

    Viatte, Sebastien; Plant, Darren; Raychaudhuri, Soumya

    2013-01-01

    Investigators have made key advances in rheumatoid arthritis (RA) genetics in the past 10 years. Although genetic studies have had limited influence on clinical practice and drug discovery, they are currently generating testable hypotheses to explain disease pathogenesis. Firstly, we review here the major advances in identifying RA genetic susceptibility markers both within and outside of the MHC. Understanding how genetic variants translate into pathogenic mechanisms and ultimately into phenotypes remains a mystery for most of the polymorphisms that confer susceptibility to RA, but functional data are emerging. Interplay between environmental and genetic factors is poorly understood and in need of further investigation. Secondly, we review current knowledge of the role of epigenetics in RA susceptibility. Differences in the epigenome could represent one of the ways in which environmental exposures translate into phenotypic outcomes. The best understood epigenetic phenomena include post-translational histone modifications and DNA methylation events, both of which have critical roles in gene regulation. Epigenetic studies in RA represent a new area of research with the potential to answer unsolved questions. PMID:23381558

  13. PERIOPERATIVE MANAGEMENT OF PATIENTS WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    V. N. Amirdzhanova

    2014-01-01

    Full Text Available The paper considers the joint management of rheumatoid arthritis patients needing endoprosthetic replacement of the large joints of the lower extremities by rheumatologists and orthopedic traumatologists.Due to the fact that there are no conventional standards or guidelines for the perioperative management of patients with rheumatic diseases, adopted by international rheumatology associations, the authors generalize their experience in managing the patients in terms of international approaches and guidelines from different countries. The medical assessment and reduction of cardiovascular risks, the prevention of infectious complications, hemorrhages, and lower extremity deep vein thrombosis, and the specific features of management of patients with osteoporosis are under consideration. The authors' experience in managing the patients receiving antirheumatic therapy with nonsteroidal antiinflammatory and disease-modifying antirheumatic drugs, such as methotrexate, leflunomide, sulfasalazine, and hydroxychloroquine, is detailed. Recommendations for managing patients taking glucocorticoids and biologic agents (tumor necrosis factor-α inhibitors, anti-B-cell therapy, and interleukin-6 receptor inhibitors in the preoperative andpostoperative periods are given.

  14. Ghrelin and obestatin levels in rheumatoid arthritis.

    Science.gov (United States)

    Koca, Suleyman Serdar; Ozgen, Metin; Aydin, Suleyman; Dag, Sait; Evren, Bahri; Isik, Ahmet

    2008-10-01

    Ghrelin is a powerful, endogenous orexigenic peptide. In addition, ghrelin has anti-inflammatory effects, and it has been reported that ghrelin down-regulates pro-inflammatory cytokines, including interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Obestatin appears to decrease food intake and appetite, and its potential role in inflammation is not yet clear. The aims of this study were to assess total and acylated (active) ghrelin and obestatin serum levels and their relations with inflammatory status in rheumatoid arthritis (RA) patients. Fasting blood samples were obtained from 37 patients with RA, 29 patients with Behçet's disease (BD) and 28 healthy controls (HC). Total ghrelin and obestatin levels were measured by radioimmunoassay and acylated ghrelin was quantified by enzyme-linked immunosorbent assay. Patients with RA had lower total ghrelin, but higher obestatin levels than patients with BD (pghrelin. Total ghrelin level was not correlated with any study parameters in the all groups. Obestatin level correlated with erythrocyte sedimentation rate and DAS-28 in the RA group, the level of IL-6 in the BD group, and with the level of TNF-alpha in the HC group (r=0.400, pghrelin and clinical or laboratory markers of disease activity in RA. Surprisingly, obestatin correlated with some inflammatory markers. So, obestatin seems to be more valuable than ghrelin in the pathogenesis of RA.

  15. A systems approach to rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Sungyong You

    Full Text Available Rheumatoid arthritis (RA is a chronic autoimmune disease that primarily attacks synovial joints. Despite the advances in diagnosis and treatment of RA, novel molecular targets are still needed to improve the accuracy of diagnosis and the therapeutic outcomes. Here, we present a systems approach that can effectively 1 identify core RA-associated genes (RAGs, 2 reconstruct RA-perturbed networks, and 3 select potential targets for diagnosis and treatments of RA. By integrating multiple gene expression datasets previously reported, we first identified 983 core RAGs that show RA dominant differential expression, compared to osteoarthritis (OA, in the multiple datasets. Using the core RAGs, we then reconstructed RA-perturbed networks that delineate key RA associated cellular processes and transcriptional regulation. The networks revealed that synovial fibroblasts play major roles in defining RA-perturbed processes, anti-TNF-α therapy restored many RA-perturbed processes, and 19 transcription factors (TFs have major contribution to deregulation of the core RAGs in the RA-perturbed networks. Finally, we selected a list of potential molecular targets that can act as metrics or modulators of the RA-perturbed networks. Therefore, these network models identify a panel of potential targets that will serve as an important resource for the discovery of therapeutic targets and diagnostic markers, as well as providing novel insights into RA pathogenesis.

  16. Sex and Management of Rheumatoid Arthritis.

    Science.gov (United States)

    Favalli, Ennio Giulio; Biggioggero, Martina; Crotti, Chiara; Becciolini, Andrea; Raimondo, Maria Gabriella; Meroni, Pier Luigi

    2018-01-26

    Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease more common in women than men (3:1). Although sex-based differences may play a complex role in promoting an autoimmune dysfunction, to date the comprehensive knowledge of the link between sex and RA is still partially lacking. Furthermore, males and females have been demonstrated to differently deal with their chronic pathologies, modifying the perceived sex-based burden of disease. Gender medicine is a newly approach focusing on the impact of gender differences on human physiology, pathophysiology, and clinical features of diseases, analyzing the complex interrelation and integration of sex and psychological and cultural behavior. A better comprehension of possible factors influencing sexual dimorphism in RA susceptibility, pattern of presentation, disease activity, and outcome could contribute to a tailored approach, in order to limit the morbidity of the disease. RA disease activity seems to be higher in women, whereas the response rate to synthetic and biologic disease-modifying therapies appears to be better in males. Moreover, the common strategies for RA management may be affected by concomitant pregnancy or childbearing desire, with particular regard to treatments with potential teratogenic effects or impact on fertility. Finally, comorbidities, such as fibromyalgia, major depression, and osteoporosis, are more frequent in females, while the impact of sex on cardiovascular risk is still controversial. Moving from the role of sex in influencing RA pathogenesis, epidemiology, and disease characteristics, this review explores the evidence on how sex can have an impact on strategies for managing patients with RA.

  17. Risk of atrial fibrillation and stroke in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Lindhardsen, Jesper; Ahlehoff, Ole; Gislason, Gunnar Hilmar

    2012-01-01

    To determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke.......To determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke....

  18. Case of physiotherapy care for patient with rheumatoid arthritis diagnosed

    OpenAIRE

    Koukalová, Martina

    2014-01-01

    Title of bachelor's thesis: Case of physiotherapy care for patient with rheumatoid arthritis diagnosed Objectives: The aim of this thesis is to show using of physiotherapeutistic methods on patient with rheumatoid arthritis. One part of this thesis is casuistry of patient with rheumatoid arthritis. The summary: The thesis is divided into two parts, the theoretical part and the special part. The theoretical part is focused on issue of rheumatoid arthritis, its characteristic, division, diagnos...

  19. Case of physiotherapy care for patient diagnosed with rheumatoid arthritis

    OpenAIRE

    Šedková, Štěpánka

    2013-01-01

    Title of bachelor's thesis: Case of physiotherapy care for patient diagnosed with rheumatoid arthritis Objectives: The aim is to emphasize the use of physiotherapy as a part of comprehensive treatment of a patient with rheumatoid arthritis. The thesis includes a detailed casuistry of a patient with rheumatoid arthritis. Methods: The thesis is divided into a general part and a special part. The general part is focused on description of rheumatoid arthritis. It discusses characteristics of the ...

  20. Serum Levels of Anticyclic Citrullinated Peptide Antibodies, Interleukin-6, Tumor Necrosis Factor-α, and C-Reactive Protein Are Associated with Increased Carotid Intima-Media Thickness: A Cross-Sectional Analysis of a Cohort of Rheumatoid Arthritis Patients without Cardiovascular Risk Factors

    Science.gov (United States)

    Vázquez-Del Mercado, Mónica; Nuñez-Atahualpa, Lourdes; Figueroa-Sánchez, Mauricio; Gómez-Bañuelos, Eduardo; Rocha-Muñoz, Alberto Daniel; Martín-Márquez, Beatriz Teresita; Martínez-García, Erika Aurora; Macias-Reyes, Héctor; Gamez-Nava, Jorge Ivan; Navarro-Hernandez, Rosa Elena; Nuñez-Atahualpa, María Alejandra; Andrade-Garduño, Javier

    2015-01-01

    The main cause of death in rheumatoid arthritis (RA) is cardiovascular events. We evaluated the relationship of anticyclic citrullinated peptide (anti-CCP) antibody levels with increased carotid intima-media thickness (cIMT) in RA patients. Methods. Forty-five anti-CCP positive and 37 anti-CCP negative RA patients, and 62 healthy controls (HC) were studied. All groups were assessed for atherogenic index of plasma (AIP) and cIMT. Anti-CCP, C-reactive protein (CRP), and levels of tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Results. The anti-CCP positive RA patients showed increased cIMT compared to HC and anti-CCP negative (P < 0.001). Anti-CCP positive versus anti-CCP negative RA patients, had increased AIP, TNFα and IL-6 (P < 0.01), and lower levels of high density lipoprotein cholesterol (HDL-c) (P = 0.02). The cIMT correlated with levels of anti-CCP (r = 0.513, P = 0.001), CRP (r = 0.799, P < 0.001), TNFα (r = 0.642, P = 0.001), and IL-6 (r = 0.751, P < 0.001). In multiple regression analysis, cIMT was associated with CRP (P < 0.001) and anti-CCP levels (P = 0.03). Conclusions. Levels of anti-CCP and CRP are associated with increased cIMT and cardiovascular risk supporting a clinical role of the measurement of cIMT in RA in predicting and preventing cardiovascular events. PMID:25821796