Rheumatoid Arthritis Research Today is a free monthly online journal that collates and summarizes the latest research about Rheumatoid Arthritis, including details on treatment, symptoms, causes, medication.

Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE transgenic mice.

Hill JA, Bell DA, Brintnell W, Yue D, Wehrli B, Jevnikar AM, Lee DM, Hueber W, Robinson WH, Cairns E

Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada, N6A 5C1.

Rheumatoid arthritis (RA) is a common autoimmune disease that afflicts the synovium of diarthrodial joints. The pathogenic mechanisms inciting this disease are not fully characterized, but may involve the loss of tolerance to posttranslationally modified (citrullinated) antigens. We have demonstrated that this modification leads to a selective increase in antigenic peptide affinity for major histocompatibility complex (MHC) class II molecules that carry the RA-associated shared epitope, such as HLA-DRB1*0401 (DR4). We describe the induction of arthritis in DR4-IE transgenic (tg) mice with citrullinated fibrinogen, a protein commonly found in inflamed synovial tissue and a frequent target of autoantibodies in RA patients. The disease induced in these mice was characterized by synovial hyperplasia followed by ankylosis, but lacked a conspicuous polymorphonuclear cell infiltrate. Immunological analysis of these mice through T cell epitope scanning and antibody microarray analysis identified a unique profile of citrulline-specific reactivity that was not found in DR4-IE tg mice immunized with unmodified fibrinogen or in wild-type C57BL/6 mice immunized with citrullinated fibrinogen, two conditions where arthritis was not observed. These observations directly implicate citrullinated fibrinogen as arthritogenic in the context of RA-associated MHC class II molecules.

Published 15 April 2008 in J Exp Med, 205(4): 967-79.
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Articles on Rheumatoid Arthritis published 10 April 2008:

Cytokines as therapeutic targets: advances and limitations.   Immunity, 28(4): 440-4.

Biological therapies targeting cytokines, T cells, or B cells have improved outcomes of inflammatory diseases. However, many issues remain open: What is the best target? How well can response be predicted? How can cure be achieved? [Abstract] [Full-text]

Articles on Rheumatoid Arthritis published 27 March 2008:

Lymphocyte-derived cytokines in inflammatory arthritis.   Autoimmunity, 41(3): 230-8.

Inflammatory bone loss is observed in a number of disorders including rheumatoid arthritis (RA), osteoporosis and periodontal disease. Lymphocytes are key components in the onset and exacerbation of autoimmune diseases and the cytokines produced by these cells have a powerful impact on disease progression. Many cytokines implicated in inflammation impact upon osteoclast (OCL) differentiation and function either directly or indirectly by modulating the relative expression of RANKL and OPG. This ... [Abstract] [Full-text]

Review: Immune cells and mediators of inflammatory arthritis.   Autoimmunity, 41(3): 224-9.

Cytokine expression in the inflamed synovial membrane of patients with rheumatoid arthritis and other forms of chronic inflammatory arthritis and other forms of chronic inflammatory arthritis leads to formation of osteoclasts. These cells are primarily involved in the resorption of mineralized cartilage and bone and thus participate in joint damage in the course of chronic arthritides. Osteoclastogenesis in the synovial membrane is driven by cytokines such as RANKL, MCSF but also classical ... [Abstract] [Full-text]

Articles on Rheumatoid Arthritis published 25 March 2008:

Mycoplasma fermentans glycolipid-antigen as a pathogen of rheumatoid arthritis.   Biochem Biophys Res Commun, 369(2): 561-6.

Mycoplasma fermentans has been suspected as one of the causative pathogenic microorganisms of rheumatoid arthritis (RA) however, the pathogenic mechanism is still unclear. We, previously, reported that glycolipid-antigens (GGPL-I and III) are the major antigens of M. fermentans. Monoclonal antibody against the GGPL-III could detect the existence of the GGPL-III antigens in synovial tissues from RA patients. GGPL-III antigens were detected in 38.1% (32/84) of RA patient's tissues, but not in ... [Abstract] [Full-text]

Articles on Rheumatoid Arthritis published 24 March 2008:

Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial.   Lancet, 371(9617): 998-1006.

BACKGROUND: Systemic-onset juvenile idiopathic arthritis does not always respond to available treatments, including antitumour necrosis factor agents. We investigated the efficacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder. METHODS: 56 children (aged 2-19 years) with disease refractory to conventional treatment were given three doses of tocilizumab 8 mg/kg every 2 weeks during a 6-week open-label lead-in phase. Patients ... [Abstract] [Full-text]

Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial.   Lancet, 371(9617): 987-97.

BACKGROUND: Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses. Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis. METHODS: In this double-blind, randomised, placebo-controlled, parallel group phase III study, 623 patients with moderate to severe active rheumatoid arthritis were randomly assigned ... [Abstract] [Full-text]

Articles on Rheumatoid Arthritis published 19 March 2008:

Responsiveness to anti-tumour necrosis factor alpha therapy is related to pre-treatment tissue inflammation levels in rheumatoid arthritis patients.   Ann Rheum Dis, 67(4): 563-6.

OBJECTIVE: The response of rheumatoid arthritis (RA) patients to treatment with neutralising antibodies to tumour necrosis factor alpha (TNFalpha) is highly variable. The underlying mechanism for therapy responsiveness is currently unknown. We therefore evaluated the relationship between baseline molecular profiles of synovial tissues from RA patients and the clinical response to treatment with infliximab. METHODS: Synovial biopsies were obtained by arthroscopy from 18 RA patients with active ... [Abstract] [Full-text]

Efficacy and safety of the selective co-stimulation modulator abatacept following 2 years of treatment in patients with rheumatoid arthritis and an inadequate response to anti-tumour necrosis factor therapy.   Ann Rheum Dis, 67(4): 547-54.

OBJECTIVE: To evaluate the safety and efficacy of abatacept during 2 years of the ATTAIN (Abatacept Trial in Treatment of Anti-TNF INadequate responders) trial in patients with rheumatoid arthritis. METHODS: Patients completing the 6-month, double-blind period were eligible to enter the long-term extension; patients received abatacept approximately 10 mg/kg, plus disease-modifying antirheumatic drugs. Safety and efficacy (American College of Rheumatology (ACR) criteria responses, DAS28 ... [Abstract] [Full-text]

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