Rheumatoid Arthritis: Burmester GR

Loddenkemper K, Burmester GR. · No affiliation provided · Arthritis Rheum. · Pubmed #18311809 links to  free full text

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Dörner T, Burmester GR. · No affiliation provided · Rheumatology (Oxford). · Pubmed #17337751 links to  free full text

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Feist E, Burmester GR. · No affiliation provided · J Rheumatol. · Pubmed #17086596 links to  free full text

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Kary S, Fritz J, Scherer HU, Burmester GR. · No affiliation provided · Rheumatology (Oxford). · Pubmed #15187247 links to  free full text

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Dörner T, Siegenthaler W, Burmester GR. · No affiliation provided · Dtsch Med Wochenschr. · Pubmed #12226786 No free full text.

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Daridon C, Burmester GR, Dörner T. · Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin and Deutsches, Rheumaforschungszentrum, Berlin 10098, Germany. · Curr Opin Rheumatol. · Pubmed #19346949 No free full text.

Abstract: PURPOSE OF REVIEW: To evaluate the impact of particular anticytokine therapies able to indirectly target B cells with emphasis on the tumor necrosis factor (TNF) family members, B cell activating factor/B lymphocyte stimulator (BAFF/BLyS) and a proliferation-inducing ligand (APRIL). RECENT FINDINGS: Although blockade of TNF/lymphotoxin by etanercept has been shown to have an impact on memory B cells, recent studies of inhibiting the TNF family members BAFF/BlyS or simultaneously blocking BAFF/BlyS and APRIL in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) clearly demonstrated biologic activity, including reductions of immunoglobulin levels. However, clear evidence of clinical activity by any of the compounds interfering with BAFF/BLys or APRIL has not yet been shown. SUMMARY: Although anticytokine therapies mainly blocking signaling pathways of innate immunity, that is TNF-alpha, have shown efficacy in the treatment of arthritides and have partial effects on memory B cells, current studies evaluate effects on adaptive immunity by blocking BAFF/BlyS and/or APRIL which indirectly act on B and plasma cells.

Dörner T, Burmester GR. · Charite Center 14, Charite University Hospital Berlin, Berlin, Germany. · Curr Opin Rheumatol. · Pubmed #18388516 No free full text.

Abstract: PURPOSE OF REVIEW: This study reviews therapeutic approaches of direct and indirect B-cell targeting in autoimmune diseases and their impact on protective immunity. RECENT FINDINGS: Beyond recent clinical experiences with rituximab as B-cell-depleting agent, other biologicals targeting CD20, such as ocrelizumab, ofatumumab, hA20, and TRU-015 mainly deplete B cells and are under clinical investigation in different entities. Moreover, anti-CD22 targeting as another approach that has been studied in clinical trials showed a modest depletion, but inhibition of B-cell activation. More indirect innovative B-cell-affecting therapies comprise blockade of cytokines, such as B-cell-activating factor (BAFF/BLyS), APRIL, and their receptors as well as blockade of costimulation. Although decreases of immunoglobulin levels were seen, so far no major increases in infections were reported. SUMMARY: The value of certain B-cell-depletion therapies as well as other therapies modulating B-cell functions needs to be further delineated, especially in the therapeutic regimen of rheumatoid arthritis, specific collagen vascular diseases and vasculitis. Long-term observations of protective immunity are also needed to further evaluate the rate of infections.

Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Sieper J, Emery P, Keystone EC, Schiff MH, Mease P, van Riel PL, Fleischmann R, Weisman MH, Weinblatt ME. · David Geffen School of Medicine, UCLA - RM 32-59, 1000 Veteran Avenue, Los Angeles, CA 90025, USA. · Ann Rheum Dis. · Pubmed #17934088 No free full text.

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Grützkau A, Grün J, Häupl T, Burmester GR, Radbruch A. · Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Charitéplatz 1, Berlin, Germany. · Dtsch Med Wochenschr. · Pubmed #17823881 No free full text.

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Feist E, Burmester GR. · Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charité-Universitätsmedizin Berlin, Berlin, Germany. · Dtsch Med Wochenschr. · Pubmed #17570088 No free full text.

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Feist E, Egerer K, Burmester GR. · Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin. · Z Rheumatol. · Pubmed #17372744 No free full text.

Abstract: Antibodies against citrullinated protein/peptides antigens (ACPA) are well recognized serological markers for rheumatoid arthritis. In addition to rheumatoid factor, they provide high diagnostic specificity and are also useful diagnostic tools in the search for early disease manifestation. As shown by several studies, both autoantibodies correlate with disease severity and the radiologic progression of rheumatoid arthritis. However, it is important to note that only the detection of rheumatoid factors is internationally standardized. Whether autoantibody profiling is also of significance for the stratification and monitoring of rheumatoid arthritis is the focus of ongoing investigations.

Scherer HU, Burmester GR. · Klinik für Rheumatologie und klinische Immunologie, Charité-Universitätsmedizin Berlin. · Dtsch Med Wochenschr. · Pubmed #17036270 No free full text.

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Martinez-Gamboa L, Brezinschek HP, Burmester GR, Dörner T. · Charité Universitätsmedizin Berlin and German Centre for Rheumatic Research (DRFZ), Schumannstr. 20/21, 10098 Berlin, Germany. · Autoimmun Rev. · Pubmed #16920569 No free full text.

Abstract: Although the immunopathogenesis of rheumatoid arthritis (RA) remains unclear, recent advances have paved the way for new therapies, such as anti-cytokine and cell-directed therapies. Here, B cells have re-gained interest concerning the pathogenesis of a number of autoimmune diseases after observing that patients with RA and non-Hodgkin lymphoma, who received anti-CD20 therapy leading to B cell depletion, demonstrated remarkable improvements. The underlying modes of action appear to be related to B cell functions, such as deletion of memory B cells, interruption of immune activation, antigen-presentation and production of inflammatory cytokines. In many RA patients, synovial extrafollicular germinal centers develop, where B cells play an intimate role in local inflammation and the generation of memory B cells and plasma cells. These local processes lead to activation of the immune system and ultimately to joint destruction in RA. Recent data demonstrating the clinical value of B cell depletion in refractory RA patients substantiate the notion that B cells are important players in the pathogenesis of the disease. Future studies should clarify which functions are affected by B cell depletion, providing the promise of new avenues to patient-tailored therapies.

Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Bijlsma JW, Dougados M, Emery P, Keystone EC, Klareskog L, Mease PJ. · 1000 Veteran Avenue Rehabilitation Centre, Room 32-59, Los Angeles, CA 90024, USA. · Ann Rheum Dis. · Pubmed #16239380 links to  free full text

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Detert J, Bastian H, Burmester GR. · Klinik für Rheumatologie und klinische Immunologie, Charité Campus Mitte, Berlin. · Dtsch Med Wochenschr. · Pubmed #16118734 No free full text.

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Buttgereit F, Song IH, Straub RH, Burmester GR. · Medizinische Klinik m.S. Rheumatologie und Klinische Immunologie, Charité-Universitätsmedizin Berlin, Schumannstr. 20/21, 10117 Berlin, Germany. · Z Rheumatol. · Pubmed #15868334 No free full text.

Abstract: Recent insights into the mechanisms of genomic and non-genomic glucocorticoid actions have stimulated the search for novel glucocorticoid receptor ligands. These efforts are driven by the need to improve the benefit-risk ratio of these important drugs. Glucocorticoids are very frequently and successfully used drugs which mediate important immunosuppressive and anti-inflammatory effects, but unfortunately they have pleiotropic effects causing a number of adverse reactions which limit their clinical use, especially at higher dosages and for longer periods. For this reason, novel glucocorticoid receptor ligands are being developed, among them selective glucocorticoid receptor agonists (SEGRAs). SEGRAs are drugs that predominantly induce transrepression effects (inhibition of protein synthesis), whereas the transactivation activity (induction of protein synthesis) is significantly reduced as compared with conventional glucocorticoid drugs. This makes sense since it became evident over the last few years that many adverse effects are predominantly caused by the transactivation mechanism, whereas anti-inflammatory effects are mostly mediated by transrepression mechanisms. Other interesting examples for exciting new developments are NO-glucocorticoids and long-circulating liposomal glucocorticoids. It is, however, true of all these developments that further in vivo and in vitro investigations and clinical trials will have to define in more detail their safety-efficacy profile in order to answer the questions whether these drugs as "improved glucocorticoids" will enter clinical medicine in the near future.

Gaber T, Dziurla R, Tripmacher R, Burmester GR, Buttgereit F. · Department of Rheumatology and Clinical Immunology, Charité University Hospital, Schumannstrasse 20/21, 10117 Berlin, Germany. · Ann Rheum Dis. · Pubmed #15800008 links to  free full text

Abstract: Maintenance of oxygen homoeostasis is the basic principle in cell proliferation, differentiation, survival, and function in all higher organisms. The transcription factor, HIF (hypoxia inducible factor) has a central role in oxygen homoeostasis, and is indispensably linked to energy metabolism. Abnormally reduced oxygen concentrations leading to dysfunctional cell metabolism are found in rheumatoid arthritis and hence, knowledge of the molecular adaptive responses to hypoxia and the involvement of HIF in the pathogenesis of RA are interesting.

Burmester GR, Häupl T. · Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Humboldt University and Free University of Berlin, Schumannstr. 20-21, 10098 Berlin, Germany. · Autoimmun Rev. · Pubmed #15546803 No free full text.

Abstract: For functional genomics of inflammatory disorders and infection, rheumatic diseases offer unique features to analyse the transition from infection to chronic inflammation, autoimmunity and immunopathology, both systemic and tissue specific. The diseases are frequent and of considerable socio-economic impact. Well-defined cohorts of patients are available. The tissues and cells involved are readily accessible for molecular analysis. Both genetic predisposition and infection are involved in the aetiopathogenesis of rheumatic diseases. The number of susceptibility and severity genes has been estimated to be at least 30, but only few of them have been identified so far. There is an urgent need for developing new therapies adapted to genetic risk and based on a functional genetic and molecular understanding of chronic inflammation. It is evident that gene analysis in inflammatory rheumatic diseases will not only be beneficial for the large number of patients involved, but will also lead to a better understanding of other inflammatory disorders, thereby possibly leading to novel diagnostic and therapeutic strategies in this important group of disorders.

Müller-Ladner U, Rüther W, Burmester GR. · Bereich Rheumatologie/Klinische Immunologie, Klinik und Poliklinik für Innere Medizin I der Universität Regensburg. · Dtsch Med Wochenschr. · Pubmed #15179592 No free full text.

Abstract: In the past years, the substantially increased number of potent drugs for the therapy of rheumatoid arthritis has made the goal of an early, highly effective therapy more feasible. In addition, combination therapy trials including biologics revealed that joint protection and downregulation of inflammation can be achieved also in stages of active articular destruction, and the detection of novel markers such as antibodies against cyclic citrullinated peptides supports an earlier diagnosis of the disease. The price for these advances, however, are more complex, demanding and expensive therapeutic regimens that need to be handled carefully by the rheumatologist, especially with regard to a new field of side effects inherent with the use of TNF inhibiting agents. Finally, the current therapeutic standard includes also the ongoing clinical and scientific exchange with the orthopedic surgeon to optimize the long-term treatment for the individual patient.

Dörner T, Egerer K, Feist E, Burmester GR. · Department of Medicine/Division of Rheumatology, Ludwigs-Maximilian University Munich, Pettenkoferstrasse 8a, D-80336 Munich, Germany. · Curr Opin Rheumatol. · Pubmed #15103252 No free full text.

Abstract: PURPOSE OF REVIEW: Initial studies of the pathogenesis of rheumatoid arthritis focused on the role of rheumatoid factor and immune complex-associated vasculitis and synovitis. Subsequent work has delineated T cell responses, the role of cytokines, chemokines, and the aggressive nature of rheumatoid synovitis. Recent findings underscore the importance of humoral immunity in this entity and are the subject of this review. RECENT FINDINGS: By the discovery of anti-cyclic citrullinated peptide, anti-RA33, and anti-GPI antibodies in the human and mouse systems, respectively, the impact of humoral autoimmunity in rheumatoid arthritis regained remarkable interest. This review summarizes recent insights into humoral autoimmunity in rheumatoid arthritis in the context of the generation of rheumatoid factors, including B cell activation via toll-like receptors and genetic predispositions that can trigger the induction of rheumatoid arthritis. The generation of rheumatoid factors that can also be found during host defense against infectious agents and under pathologic conditions, such as rheumatoid arthritis, Sjögren syndrome, and hepatitis C-associated mixed cryoglobulinemia after hepatitis C infection is likely the result of genetic predispositions and the intensity of the (primary) immune reaction. Models of the role of rheumatoid factors in health and disease, including related lymphomagenesis, will be discussed. SUMMARY: In patients with rheumatoid arthritis, the induction of rheumatoid factors can be taken as an indicator of severe disease with a striking involvement of B cell activation. Very recent clinical trials using B cell depletion support the concept that humoral immunity, as evidenced by the production of rheumatoid factors, plays a significant role in the course of the disease.

Brunner-Weinzierl MC, Hoff H, Burmester GR. · Molecular Immunology, Deutsches Rheuma-Forschungszentrum Berlin, Germany. · Arthritis Res Ther. · Pubmed #15059264 links to  free full text

Abstract: Chronic T cell responses, as they occur in rheumatoid arthritis, are complex and are likely to involve many mechanisms. There is a growing body of evidence that, in concert with the T cell antigen receptor signal, CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) are the primary regulators of T cell responses. Whereas CD28 primarily activates T cell processes, CTLA-4 inhibits them. The mechanism for this dichotomy is not fully understood, especially as CD28 and CTLA-4 recruit similar signalling molecules. In addition, recent studies demonstrate that CD28 and CTLA-4 have multiple functions during T cell responses. In particular, CTLA-4 exerts independent distinct effects during different phases of T cell responses that could be exploited for the treatment of rheumatoid arthritis.

Kary S, Buttgereit F, Burmester GR. · Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Universitätsklinikum Humboldt Universität Berlin. · Internist (Berl). · Pubmed #14671809 No free full text.

Abstract: The optimal drug therapy of inflammatory rheumatic diseases is based on an individual concept of treatment combining several antirheumatic drugs with different modes of acting. In treating older patients this individual concept has to consider special conditions, as these patients often receive further medications due to different indications so that pharmacologic interactions and comorbidity have to be taken into account. Recently, new substances like COX-2-inhibitors, the new disease modifying antirheumatic drug (DMARD) Leflunomide and particularly the cytokine-blockers provide new and highly effective treatment options. The administration of these drugs in elderly patients is discussed.

Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Dougados M, Emery P, Gibofsky A, Kavanaugh AF, Keystone EC, Klareskog L, Russell AS, van de Putte LB, Weisman MH, Kavenaugh AF. · University of California, UCLA, Rheumatology, Division Los Angeles, USA. · Ann Rheum Dis. · Pubmed #14532138 links to  free full text

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Feist E, Burmester GR, Dörner T. · Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie, Universitätsklinikum Charité Humboldt-Universität zu Berlin, Berlin, Germany. · Z Rheumatol. · Pubmed #12928940 No free full text.

Abstract: New strategies including the blockade of TNFalpha showed excellent therapeutic effects even in so far refractory rheumatic diseases. Moreover, these approaches provided us with important informations about the pathogenic role of the mediators involved and distinct autoimmune cellular subsets. Here, we discuss recent data of a temporary B cell depletion using a monoclonal anti-CD20 antibody in the therapeutic arsenal of rheumatoid arthritis.

Lindenau S, Scholze S, Odendahl M, Dörner T, Radbruch A, Burmester GR, Berek C. · Deutsches Rheumaforschungszentrum, Berlin, Gemany. · Ann N Y Acad Sci. · Pubmed #12727646 No free full text.

This publication has no abstract.