Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
17309133 Incidence of tuberculosis in Korean patients with rheumatoid arthritis (RA): effects of RA 2007 Apr OBJECTIVE: To elucidate the incidence rate and relative risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) and in patients with RA treated with tumor-necrosis-factor (TNF) blockers in Korea. METHODS: Using data from the Korean National Tuberculosis Association (KNTA) as a control and data from a single-center cohort of patients with RA, we conducted an evaluation of 1285 patients with RA not exposed to TNF blockers and reviewed medical records of 90 and 103 patients with RA treated with infliximab and etanercept, respectively, between 2001 and 2005. RESULTS: The mean incidence rate of TB, reported by the KNTA, was 67.2 per 100,000 person years (PY) from 2001 to 2004. In the TNF-blocker-naïve RA cohort, 9 cases of TB developed during 3497 PY of followup (257 per 100,000). In the infliximab-treated RA group, 2 cases of TB developed during 78.17 PY of followup (2558 per 100,000 PY), and there was no case of TB during 73.67 PY of followup in the etanercept-treated RA group. The risk of TB was higher in RA patients not treated with TNF blockers (sex- and age-adjusted risk ratio 8.9; 95% confidence interval 4.6-17.2), and in those treated with infliximab (sex- and age-adjusted risk ratio, 30.1; 95% confidence interval, 7.4-122.3) compared with the general Korean population. CONCLUSION: The risk of TB infection is 8.9-fold higher in Korean patients with RA and 30.1-fold higher in RA patients treated with infliximab, compared with the general Korean population.
18438854 Reciprocal cross-talk between RANKL and interferon-gamma-inducible protein 10 is responsib 2008 May OBJECTIVE: Interferon-gamma-inducible protein 10 (IP-10; also called CXCL10), a chemokine important in the migration and proliferation of T cells, is induced in a wide variety of cell types. However, the role of IP-10 in rheumatoid arthritis (RA) remains largely unknown. The purpose of this study was to examine the potential role of IP-10 in bone resorption and RA through examination of a mouse model of collagen-induced arthritis (CIA). METHODS: The effects of IP-10 on mouse T cells during osteoclast differentiation were examined in migration assays. The bone-erosive activity of IP-10 was determined in vivo in a mouse model of CIA by histologic and immunostaining analyses. Cytokine levels in serum and culture medium were measured with sandwich enzyme-linked immunosorbent assays. RESULTS: Serum concentrations of IP-10 were significantly higher in mice with CIA than in control mice. RANKL greatly induced IP-10 expression in osteoclast precursors, but not in mature osteoclasts. IP-10 stimulated the expression of RANKL and tumor necrosis factor alpha (TNFalpha) in CD4+ T cells and induced osteoclastogenesis in cocultures of CD4+ T cells and osteoclast precursors. However, IP-10 did not induce RANKL or TNFalpha in CD8+ T cells. Treatment with neutralizing antibody to IP-10 significantly inhibited the infiltration of CD4+ T cells and F4/80+ macrophages into the synovium and attenuated bone destruction in mice with CIA. Furthermore, levels of RANKL and TNFalpha were inhibited by antibody to IP-10. Bone erosion was observed in mice infected with an IP-10 retrovirus. CONCLUSION: Our findings suggest that IP-10 plays a critical role in the infiltration of CD4+ T cells and F4/80+ macrophages into inflamed joints and causes bone destruction. Our results provide the first evidence that IP-10 contributes to the recruitment of inflammatory cells and is involved in bone erosion in inflamed joints.
18187523 MAPKs and their relevance to arthritis and inflammation. 2008 Apr Rheumatoid arthritis (RA) is a chronic autoimmune disease in which imbalances in pro- and anti-inflammatory cytokines promote the induction of autoimmunity, inflammation and joint destruction. The importance of inflammatory cytokines in the pathogenesis of RA has been underscored by the success of biologics that act to block the effects of cytokines, such as tumour necrosis factor-alpha, interleukin (IL)-1 or IL-6, in treating disease. Mitogen-activated protein kinases (MAPKs) have been implicated as playing key regulatory roles in the production of these pro-inflammatory cytokines and downstream signalling events leading to joint inflammation and destruction. This article reviews the evidence that MAPKs play important roles in the pathogenesis of RA and discusses their therapeutic potential as drug targets.
18493770 Improved rheumatoid digital vasculitis in a patient treated with TNFalpha agent blocking ( 2008 Oct Rheumatoid vasculitis (RV) is an uncommon but potentially catastrophic complication of rheumatoid arthritis (RA). There are few current extensive studies and no consensus regarding the clinical, laboratory, histologic features and management or prognosis of RV. We report a case of RV in a 74-year old woman with a long (14 years) history of RA, who developed vasculitis of distal arteries with gangrene of digits of upper and lower extremities. After the failure of various immunosuppressive drugs (cyclophosphamide, methotrexate), the patient was treated with anti-TNFalpha infliximab. Digital gangrene healed within four months from the start of anti-TNFalpha treatment.
18551934 Soluble transferrin receptor, ferritin and soluble transferrin receptor--Ferritin index in 2007 Oct Anaemia of chronic disease (ACD) is a frequent complication of rheumatoid arthritis (RA). A diagnostic difficulty in RA is the distinction between iron deficiency anaemia (IDA) and ACD. The aim of our study was to evaluate the usefulness of serum soluble transferrin receptor (sTfR) and sTfR/log ferritin (TfR-F) index to diagnose iron deficiency in RA patients with anaemia. Routine laboratory indices of anaemia and sTfR were measured in 20 healthy persons to form the control group, 30 patients with iron deficiency anaemia and 28 RA patients with anaemia. Serum sTfR levels were significantly elevated above the cut-off value in patients with IDA and those in the iron depleted RA subgroup (ferritin < 60 microg/L) compared with those in the control and iron repleted RA subgroup (ferritin > 60 microg/L). The same was observed for TfR-F index. However, five patients in the iron repleted RA sub group had an elevated sTfR level, of which two had increased TfR-F index. Serum sTfR correlated well with the markers of anaemia and not with ESR. Ferritin had no correlation with markers of anaemia but correlated well with ESR. Measurement of sTfR and TfR-F index are good indicators of iron deficiency in RA patients with anaemia. To be cost effective, sTfR can be estimated in RA patients with anaemia when the ferritin level is more than 60 microg/L.
17426358 Auto-antibodies and autoreactive T-cells in rheumatoid arthritis: pathogenetic players and 2007 Feb Rheumatoid arthritis (RA) is not only the most severe of all joint diseases but also the most common systemic autoimmune disease affecting approximately 1% of the world-wide adult population. RA is characterized by the presence of autoantibodies in serum and synovial fluid distinguishing the disease from other arthritides such reactive arthritis or osteoarthritis. Since the historical description of rheumatoid factor (RF), which is an autoantibody directed to immunoglobulin G, numerous additional autoantibodies have been discovered in sera of RA patients. These antibodies may be directed to cartilage components, stress proteins, enzymes, nuclear proteins and, most importantly, citrullinated proteins such as fibrin or vimentin. In contrast to other antibodies including RF, anti-citrullinated protein antibodies are targeted almost exclusively by RA patients thus being the most specific serological markers of RA. Even though most other antibodies are not used for diagnostics, they may contribute to the patholophysiology of RA by forming immune complexes in the joint. Furthermore, autoreactive T-cells in serum and synovial fluid may initiate or enhance the disease process via production of proinflammatory cytokines leading to autoantibody secretion, stimulation of macrophages and activation of bone resorbing osteoclasts. Identification of novel autoantigens, particularly citrullinated proteins, and the characterization of the cellular and molecular processes underlying the autoimmune reactions against them has provided new insights into the complex pathogenesis of RA. This has made possible the development of novel therapeutic concepts that may allow to treat the disease more effectively in its early stages where the chances are highest to interrupt the deleterious processes.
17984576 [Therapeutic potential of phosphoinositide 3-kinase inhibitors in rheumatoid arthritis]. 2007 Oct Activation of PI3K is a key step of intracellular signaling involved in many cellular functions. PI3K inhibitors have shown anti-rheumatic effects on arthritis model in mice. PI3K is a potential therapeutic target of rheumatoid arthritis.
18638466 Anti-cyclic citrullinated peptide antibodies in lung diseases associated with rheumatoid a 2008 Sep OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific markers for rheumatoid arthritis (RA) and useful for predicting RA development and progression. However, it has not been fully determined whether anti-CCP antibodies are associated with pulmonary diseases in RA patients. In the present study, we aimed to elucidate the relationships between anti-CCP antibodies and pulmonary diseases, particularly interstitial lung disease (ILD) and bronchiolitis. DESIGN AND METHODS: Using an enzyme-linked immunosorbent assay, the presence of serum anti-CCP antibodies was examined in 18 RA patients with ILD and bronchiolitis who were diagnosed based on pathologic findings. A further 36 RA subjects without any pulmonary diseases served as a reference population. RESULTS: No significant differences were found for the prevalences and levels of anti-CCP antibodies between patients with and without ILD and follicular bronchiolitis. CONCLUSION: Detection of serum anti-CCP antibodies has no association with pulmonary diseases in RA patients.
18253109 Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or 2008 Mar Metalloproteinases such as the matrix metalloproteinases (MMPs) and disintegrin-metalloproteinases with thrombospondin motifs (ADAMTSs) have been implicated in the pathological destruction of joint tissues in rheumatoid arthritis and osteoarthritis. These enzymes degrade extracellular matrix macromolecules and modulate factors governing cell behavior. They may also be involved in tissue repair, but become a part of the destructive disease process due to overexpression. Studies investigating the roles of metalloproteinases have thrown light on the failure of the early clinical trials of MMP inhibitors as therapeutic agents in arthritic diseases. It is now clear that a more accurate knowledge of the enzymes in the different cells and their precise roles in the disease process is required for these approaches to be successful. The next generations of metalloproteinase inhibitors should have added specificity, gained from an understanding not only of the catalytic domain structures but the role of extracatalytic motifs in substrate binding, or by the generation of engineered tissue inhibitors of metalloproteinases. Inhibition of the enzymes by modulating gene expression or preventing protein activation could also be considered. Work on the development of effective biomarkers is also essential before an effective evaluation of the new generations of specific inhibitors can be made.
17673196 Identification of a predictive biomarker for the beneficial effect of a Kampo (Japanese tr 2007 Oct OBJECTIVES: Kampo (Japanese traditional herbal) medicines are now ethically used in Japan as pharmaceutical grade prescription drugs. However, there are distinct groups of responders and non-responders to Kampo medicines. We searched for biomarker candidates to discriminate responders from non-responders to keishibukuryogan (KBG); one of the most frequently used Kampo medicines. DESIGN AND METHODS: A combination of SELDI technology and a decision tree analysis with proprietary developed bioinformatics tools was applied to 41 (32 for tree construction and 9 for validation test) plasma samples obtained from rheumatoid arthritis (RA) patients. A candidate biomarker protein was identified using LC-MS/MS. RESULTS: The constructed tree with measurable reliability contained only a single peak which was identified as haptoglobin alpha 1 chain (Hpalpha1). CONCLUSION: Hpalpha1 is a biomarker candidate for discriminating responders from non-responders to KBG treatment for RA. The present results may open the way to the establishment of "evidence-based" complementary and alternative medicine.
17343253 Ultrasonography and magnetic resonance imaging of heel fat pad inflammatory-oedematous les 2006 Nov OBJECTIVE: To study heel fat pad (HFP) inflammatory-oedematous lesions in selected patients with rheumatoid arthritis (RA) using ultrasonography (US) and power Doppler US (PDUS), to describe and compare US features of these lesions with those obtained with magnetic resonance imaging (MRI), and to describe changes in the lesions after a short-term follow-up with conventional or anti-tumour necrosis factor-alpha (TNFalpha) therapy. METHODS: Twelve heels of eight RA outpatients with HFP inflammatory-oedematous lesions were studied by US, PDUS, and unenhanced MRI. All the patients were followed up and US was performed after 3 months. Five patients started on anti-TNFalpha therapy. RESULTS: HFP lesions appeared at US as a heterogeneous and hypoechoic subcalcaneal mass, with loss of normal lobular structure and increased thickness of HFP, because of focal rupture of fibrous septae with oedema and fluid. PDUS showed peripheral vascularization of HFP lesions in 9/12 heels. In 3/12 heels some vascular signals was also detectable inside the lesion, always along the residual echoic septa. No detectable flow was observed within the central fluid-filled spaces. MRI of the HFP lesions showed areas of mean intensity in T1-weighted sequences and high intensity in T2-weighted sequences, with poorly or well-defined margins. After 3 months, PDUS showed reduction in HFP lesion vascularity (associated with reduction in pain) in 10/12 heels, while poor regression of grey-scale US abnormalities was observed. CONCLUSIONS: Both US and MRI are capable of demonstrating structural abnormalities in the HFP. PDUS is useful to assess and monitor inflammatory vascularization of the HFP lesions.
17302060 [Exploration on relationship between platelet count and efficacy of Chinese medicine and W 2007 Jan OBJECTIVE: To explore the correlationship between platelet count and efficacy of traditional Chinese medicine (TCM) or Western medicine (WM) in treating rheumatoid arthritis (RA) patients. METHODS: A total of 356 patients with confirmed diagnosis of active RA from 9 clinical centers were randomly assigned to the TCM group (184 cases) and the WM group (172 cases). The TCM group was treated with basic therapy (administration of glucosidorum tripterygll totorum and Yishen Juanbi Pill) and TCM syndrome differentiation dependent treatment, while the WM group was treated with non-steroidal anti-inflammatory drugs and slow-acting anti-rheumatic drugs. The therapeutic efficacy was assessed with ACR20, the joint damage degree of both hands was evaluated by X-ray. RESULTS: The platelet count was positively correlated to the X- ray grading of joint damage, namely, patients with a more severe joint damage often presented a higher platelet count. After treatment, in patients with joint damage of X-ray grade II or III and effectively treated with TCM, also in patients with joint damage of grade III and effectively treated with WM, the platelet count was lower than that in those treated ineffectively. CONCLUSION: Platelet count is closely correlated to the efficacy of drug therapy, therefore, it may be taken as an important index for judging the curative effect of therapeutic approach in treating RA patients.
17417990 Erosive arthropathy: clinical variance in lupus erythematosus and association with anti-CC 2007 Jan OBJECTIVE: To describe the occurrence of erosive arthropathy in systemic lupus erythematosus (SLE) and its relationship to anti-CCP antibodies. METHODS: Retrospective medical record review of a case series of five female patients with SLE and erosive arthropathies. RESULTS: The initial disease presentation in all patients was a polyarthritis. Anti-CCP antibodies were detected in 4 out of 5 (80%) patients, 2 of whom had a positive rheumatoid factor. CONCLUSION: Erosive arthritis was strongly associated with the presence of anti-CCP antibodies in these patients with SLE, who presented with polyarthritis. Anti-CCP in patients with SLE may be a marker of a more severe joint disease.
19030862 The Val762Ala polymorphism in the poly(ADP-ribose) polymerase-1 gene is not associated wit 2009 May The findings of the studies on poly(ADP-ribose) polymerase-1 (PARP-1) have suggested that the enzyme inactivation provides significant protection against systemic or tissue inflammation in animal models. It has also shown that the single-nucleotide polymorphism (Val762Ala) of the PARP-1 causes about 40% decrease of enzyme activity. The aim of this study was to analyze the association of the PARP-1 Val762Ala polymorphism in Turkish patients with rheumatoid arthritis. A total of 128 RA patients and 165 normal controls from the same geographic region were studied and polymerase chain reaction (PCR)-based restriction analysis was used to identify Val762Ala polymorphism of the PARP-1. Association analyses were performed using chi (2) tests. Our results indicated that the distribution of the PARP-1 genotypes and alleles did not differ significantly among subjects with or without RA (P > 0.05). The results of the study indicate that, for our Turkish sample, the V762A polymorphism of the PARP-1 may not be involved in susceptibility to RA, implying that the polymorphism may not function as a candidate gene marker for screening RA patients.
18034202 Infection of total hip prosthesis by Mycobacterium tuberculosis and Mycobacterium chelonae 2008 Apr Atypical mycobacterial infections of the musculoskeletal system are very rare and are generally associated with predisposing factors, such as trauma, use of corticosteroids, or an immunocompromised state. There have only been three reports of Mycobacterium chelonae prosthetic infection of which two cases were associated with total hip arthroplasty and one with total knee arthroplasty and no reports of both Mycobacterium tuberculosis and M. chelonae occurring in the same joint. We report a case of a patient with rheumatoid arthritis treated with low-dose methotrexate (15 mg/week) who developed infection with both M. tuberculosis and M. chelonae after the revision of a prosthetic hip. Joint infections by mycobacteria are clinically indistinguishable from those caused by more common bacterial pathogens and, therefore, diagnosis is often delayed. Recurrent prosthetic hip infections, particularly in immunosuppressive patients, should alert the physician to consider the possibility of both tuberculous and atypical mycobacterial infections. Obtaining appropriate cultures can be critical in making the diagnosis and directing treatment. With the increasing use of immunosuppressive agents, including TNF alpha inhibitors, it is likely that there will be an increase in the number of mycobacterial infections complicating arthroplasties.
17968549 Leptin serum levels in rheumatoid arthritis patients: relation to disease duration and act 2008 Apr Leptin is a peptide hormone with the tertiary structure of a cytokine, which not only regulates body weight by inhibiting food intake, but also modulates inflammatory and immune responses. The aim of the study was to investigate if there are connections between leptin concentrations and parameters of nutritional status and disease activity in a group of rheumatoid arthritis (RA) patients. The study group consisted of 37 patients. The mean leptin serum concentration was significantly higher in women than in men. The leptin concentrations correlated positively with BMI only in women with RA. The leptin concentrations were significantly higher in patients with erosive RA. Assessing the group of patients with long-standing RA (duration > 10 years), we found that leptin levels were significantly higher in patients with higher disease activity than in those with DAS28 < or = 5,1; there was also a positive correlation between serum leptin concentration and the value of DAS28, ESR and the number of tender joints. The results suggest that some important dependence exists between the risk of aggressive course of RA and increased leptin levels.
17932479 A rare case of systemic autoimmune disease with intricate features of systemic sclerosis, 2007 Jul We report an unusual case of connective tissue disease characterized by the coexistence of signs, symptoms and immunological features of 4 defined autoimmune diseases: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis (PM) and rheumatoid arthritis (RA). A 53-year-old female was admitted in our clinic with massive polyserositis (pretamponade) as well as skin, joint, muscular lesions and altered general status. The problem we found was the difficulty of including this case in a known clinical entity; SSc/SLE/PM//RA overlap syndrome and mixed connective tissue disease were the two most plausible diagnoses. We discuss the particularities of these clinical and immunological associations and the appropriate therapeutic options used in this kind of patients.
17036499 [Clinical image of oral mucous membrane in rheumatoid arthritis patients]. 2006 The aim of the study was to evaluate the character and frequency of pathological changes in the oral cavity mucous membrane and xerostomy in patients with prolonged hospital and ambulatory treatment due to rheumatoid arthritis (RA). EXAMINATION MATERIAL: The study was conducted in 120 patients with RA, average age 54, and in the control group of 40 generally healthy examinees, average age 53. RESULTS: In patients with RA pathological changes in the oral cavity appeared much more frequently: erosions, fissures, perleche, candidiasis oris, lichen Wilsoni, leukoplakia and persistent xerostomy. RA patients more often used partial prosthesis and more frequently were edentulous. CONCLUSIONS: The treatment of oral cavity diseases and prophylaxis should be provided together with the RA treatment, with special emphasis put on the elimination of xerostomy. Good cooperation of rheumatologists and periodontologists is recommended RA diagnosis.
17159837 [Periodontal tissues state in patients with systemic osteoporosis]. 2006 The results of the study of periodontal tissues in patients with systemic osteoporosis in rheumatoid arthritis are presented. The reduction of bone density in the region of interalveolar septa, insignificant bone tissue loss of the horizontal type and pathological teeth mobility were reported.
16873089 Immunomodulatory effects of lingzhi and san-miao-san supplementation on patients with rheu 2006 Rheumatoid arthritis (RA) is an autoimmune joint disease. We evaluated a standard preparation of Lingzhi (Ganoderma lucidum) and San-Miao-San (Rhizoma atractylodis, Cortex phellodendri, Radix achyranthes bidentatae) capsules (TCM group) for its supplementary treatment efficacy for RA. There was no significant difference in the absolute count, percentage, and ratios of CD4(+)/CD8(+)/natural killer/B lymphocytes between the TCM and placebo groups after taking the capsules (all p > 0.05). There was no significant change in concentrations of plasma cytokines of interferon-gamma-induced protein-10 (IP-10), monocyte chemoattractant protein-1, monokine induced by IFN-gamma, regulated upon activation normal T-cell expressed and secreted, interleukin (IL)-8, and IL-18 after taking the capsules for 8 and 24 weeks (all p > 0.05). The percentage change in ex vivo-induced level of inflammatory cytokine IL-18 was significantly lower in the TCM group than in the placebo group after taking the capsules for 24 weeks (p < 0.05). Therefore, Lingzhi and San-Miao-San capsules might exert a beneficial immunomodulatory effect in patients with rheumatoid arthritis.