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ID PMID Title PublicationDate abstract
12208180 Rheumatoid arthritis is auto-immunoreaction to collagen II in cartilage happened in synovi 2002 Oct Rheumatoid arthritis is complex and not clear on the mechanism of pathogenesis. On the basis of analysis of the symptom and pathology of rheumatoid arthritis patients, we raised a new hypothesis. The content of the hypothesis is as follows: (A) Collagen II or collagen II-Iike substance in human cartilage is the cross-autoantigen of some infecting virus or bacteria because of the structure's similarity. (B) The inflammation in synovial tissue is auto-immunoreaction to collagen II in cartilage. (C) The proliferation and attachment of synovial tissue to the surface of cartilage is due to the chemotaxis of collagen II in cartilage for the immunocytes in synovial tissue. (D) The collagenase secreted from synovial cells and immunocytes are the direct elements in the destruction of cartilage. The fallen collagen II from cartilage is one of the most important inducer on the synovial cells and immunocytes for the production of collagenase.
11927997 Hy-Flex II total knee system and range of motion. 2002 Apr We developed the Hy-Flex II total knee and ligament balancing system (Hy-Flex II total knee) which provides (1) a flexion angle of at least 120 degrees or more, (2) a range of motion (ROM) comparable to or greater than that before surgery, and (3) occasional full flexion. The system design has several features: small posterior femoral condyle radius, a 4 degrees posterior tilting of the tibial joint surface, and equal tension of the bilateral soft tissues obtained by using a ligament tensor. From September 1997 to June 1999, Hy-Flex II total knee arthroplasty was carried out on 114 joints of 84 patients with rheumatoid arthritis. One year after surgery, the average flexion in our series was 122.1 degrees +/-15.0 degrees. The number of knees operated on which had a flexion angle of 120 degrees or greater was 82 (71.9%) 1 year after surgery among the total of 114 knees. In total, 94 (82.5%) joints obtained the same level or better than the preoperative flexion; 26 (22.8%) attained full flexion 4 weeks after the operation and 15 (13.1%), 1 year after the operation. These results suggest that this system will be able to achieve our aims in almost all rheumatoid knees.
15361125 Intercellular adhesion molecule-1 polymorphisms in Korean patients with rheumatoid arthrit 2004 Oct Rheumatoid arthritis (RA) is characterized by synovial proliferation and the accumulation of inflammatory cells in the affected joints. Intercellular adhesion molecule-1 (ICAM-1) is readily detected in RA synovial tissues and helps recruit inflammatory cells to the joint. ICAM-1 shows genetic polymorphisms at codons 241 (R241G) and 469 (K469E). In order to investigate the association between ICAM-1 gene polymorphisms and RA, we genotyped ICAM-1 R241G and ICAM-1 K469E polymorphisms in 143 Korean patients with RA, and in 138 healthy controls, by using the polymerase chain reaction-restriction fragment length polymorphism method. No polymorphism of R241G was found in Korean subjects. However, the frequency of the K469 allele was found to be significantly lower in RA patients than in healthy controls. Allele frequency of K469 was lower in RA patient group, compared to that in healthy controls, regardless of the shared epitope status. Distribution of K469E allele frequencies was not different whether the patient had rheumatoid factor, radiographic erosion or extra-articular complications. In conclusion, this study shows lower frequency of the ICAM-1 K469E allele in Korean patients with RA than that in healthy controls.
12399885 [Effects of the chemokine MIP-1alpha on anemia and inflammation in rheumatoid arthritis]. 2002 Oct Macrophage inflammatory protein-1alpha (MIP-1alpha) is an interesting chemokine because in addition to its variety proinflammatory activities including chemotaxis and immunomodulation, it is a potent inhibitor of hematopoetic stem cell proliferation. Inhibition of erythroid progenitor cells due to MIP-1alpha or other cytokines can play a role in the pathogenesis of anemia which is one of the most common extra-articular features of active rheumatoid arthritis (RA). In 84 patients with RA, serological and immunological parameters were assessed to detect inflammatory mechanisms and anemia in relation to the serum concentrations of MIP-1alpha. All patients fulfilled the ACR criteria for the diagnosis of a definite or classic RA. We used a quantitative enzyme immuno assay for the detection of MIP-1alpha as well as for the measurement of the acute phase protein serum amyloid A (SAA), the erythropoiesis inducer erythropoietin (EPO) and the transferrin receptor (TfR). The immune activation marker neopterin was measured radioimmunologically. Half of the patients with RA were anemic with hemoglobin values below 12 g/dl. MIP-1alpha was found to be elevated significantly in serum of patients with active rheumatoid arthritis and in patients with anemia. Most of the anemic patients with markedly elevated acute phase reactions had an anemia with chronic diseases and not a functional iron deficiency alone. TfR correlated with EPO. The results show that enhanced expression of MIP-1alpha is indicative of systemic inflammation in RA. Moreover, besides the regulation of inflammatory processes, this chemokine may influence the pathogenesis of anemia in RA patients.
15077265 The clinical effect of glucocorticoids in patients with rheumatoid arthritis may be masked 2004 Apr 15 OBJECTIVE: Our previous analysis of patients with early active rheumatoid arthritis (RA) treated with prednisone or placebo revealed the following discrepancy: although a significant retardation of joint damage was observed in the prednisone group compared with the placebo group, no differences in clinical variables between the 2 groups were observed, due to greater use of additional therapy in the placebo group. We sought to investigate whether this discrepancy would extend to variables of well-being. METHODS: We conducted a double-blind, randomized, placebo-controlled clinical trial of prednisone (10 mg) in patients with RA; the duration of the study was 2 years. Following the placebo-controlled trial, a 1-year open-label followup study was conducted in 81 patients with early (
12695163 Circulating tumour necrosis factor alpha and soluble tumour necrosis factor receptors in p 2003 May OBJECTIVE: To examine the relation between the serum levels of tumour necrosis factor alpha (TNFalpha), soluble tumour necrosis factor receptors (sTNF-R), and the histological pattern of rheumatoid synovitis. METHODS: An enzyme linked immunosorbent assay (ELISA) was used to measure TNFalpha, p55 sTNF-R, and p75 sTNF-R concentrations in the serum of 43 patients with rheumatoid arthritis (RA) and 34 patients with osteoarthritis (OA). RESULTS: Upon histological analysis two variants of rheumatoid synovitis emerged. Twenty six RA specimens presented only diffuse infiltrates of mononuclear cells. In the remaining 17 samples the formation of lymphocytic follicles with germinal centre-like structures was found. Serum concentrations of TNFalpha, p55 and p75 sTNF-R were raised in patients with RA compared with the OA control group (p<0.001 for all comparisons). Levels of TNFalpha, p55 and p75 sTNF-R were higher in the serum of patients with RA with follicular synovitis than in patients with diffuse synovitis (p<0.001, p<0.01, and p<0.05, respectively). Serum concentrations of TNFalpha, p55 and p75 sTNF-R correlated with markers of disease activity. CONCLUSION: Different histological types of rheumatoid synovitis associated with distinct serum levels of TNFalpha and sTNF-R reflect varying clinical activity of the disease and support the concept of RA heterogeneity.
12073751 Selection bias due to non-response in a health survey among patients with rheumatoid arthr 2002 Jun BACKGROUND: Non-response may lead to bias in health(care) outcomes. METHODS: We compared respondents (n = 334) to a questionnaire survey among patients with rheumatoid arthritis with non-respondents (n = 68) and determined predictors of (non-)response. The bias in prevalence estimates of health characteristics and health care use was quantified. RESULTS: Self-reported pain and health care utilization were the most important predictors of (non-)response with respondents experiencing pain more often and more often using specific health care services. Bias concerned especially an underestimation of 'never having pain' (60%) and 'no contact with health care services' (51%). CONCLUSION: More insight into the phenomenon of non-response is important to assess disease burden and health care burden more precisely.
15517620 Wnt1 inducible signaling pathway protein-3 regulation and microsatellite structure in arth 2004 Nov OBJECTIVE: Rheumatoid arthritis (RA) synovial tissue expresses several embryonic gene families, including wingless (wnt) and their receptors, frizzled (fz). The Wnt proteins, including Wnt-1, activate the Wnt inducible signaling pathway proteins (WISP), which are members of the CCN family that regulate cell growth and differentiation. WISP3 is of particular interest because it contains a microsatellite region in its coding region that is susceptible to frameshift mutations and leads to a truncated protein. To investigate the contribution of WISP3 to synovial inflammation, we evaluated its expression and regulation in arthritis. METHODS: mRNA and protein expression of WISP3 were determined by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis, respectively. For mutation analysis, PCR product amplified from genomic DNA of synovial tissue and cultured fibroblast-like synoviocytes (FLS) was subcloned and sequenced. RESULTS: WISP3 mRNA is expressed in synovial tissue, but is 11-fold higher in RA than osteoarthritis (OA) or normal samples. Surprisingly, WISP3 protein levels are similar in RA, OA, and normal synovium samples. Immunohistochemistry of synovial tissue reveals that WISP3 protein is located primarily in the synovial intimal lining. WISP3 mRNA expression is also 6-fold higher in RA FLS compared with OA FLS and 50-fold higher in RA than in normal FLS. When RA FLS are stimulated with interleukin 1 or tumor necrosis factor-a, WISP3 mRNA is significantly increased. The cytokines also increase WISP3 mRNA in OA FLS, but the maximal level in stimulated OA FLS is still less than medium-treated RA FLS. Mutation analysis in the coding region microsatellite of the WISP3 gene in RA and OA synovium and FLS shows a limited number of insertion and deletion mutations. CONCLUSION: WISP3 gene expression is higher in RA synovium and FLS compared with OA and normal synovial tissue and is further induced by proinflammatory cytokines in vitro. Protein levels are not increased, indicating discoordinate regulation of WISP3 protein and mRNA. Although functionally relevant mutations were observed in genomic DNA, they were noted in both OA and RA samples.
12832710 Activated leucocytes express and secrete macrophage inflammatory protein-1alpha upon inter 2003 Nov OBJECTIVE: To examine the expression and regulation of chemotactic factor, macrophage inflammatory protein-1alpha (MIP-1alpha) by fibroblast-like synoviocytes (FLS), monocytes and polymorphonuclear neutrophils (PMN) isolated from the synovial fluid (SF) of rheumatoid arthritis (RA) patients. METHODS: Monocytes or PMN obtained from RA SF were co-cultured with unstimulated semiconfluent RA FLS. Culture supernatants were assayed for MIP-1alpha by enzyme-linked immunosorbent assay. The expression of MIP-1alpha mRNA and protein was also determined by Northern blot analyss and immunohistochemistry respectively. RESULTS: Interaction of activated leucocytes with FLS synergistically increased MIP-1alpha expression and secretion via a mechanism mediated by beta2-integrin/ intercellular adhesion molecule 1. CONCLUSION: MIP-1alpha expression within inflamed joints appears to be regulated not only by inflammatory cytokines but also by the physical interaction of activated leucocytes and FLS, and plays a crucial role in the progression and maintenance of RA synovitis.
14713577 Low-dose radiotherapy (LD-RT) and the modulation of iNOS expression in adjuvant-induced ar 2003 Dec PURPOSE: Low-dose radiotherapy (LD-RT) of arthritic joints applied during the peak of the acute inflammatory response improves the clinical and histomorphological development of adjuvant arthritis. The study was undertaken to investigate the cellular composition of the inflammatory infiltrate and the expression of the pro-inflammatory and anti-inflammatory enzymes, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX-2) and haem-oxygenase 1 (HO-1), in response to LD-RT. MATERIALS AND METHODS: Adjuvant arthritis in female Lewis rats was induced by intradermal injection of heat-inactivated mycobacterium tuberculosis on day 0. Both arthritic hind paws were sham irradiated (group 1) or X-irradiated with either 5 x 1.0 Gy (group 2) or 5 x 0.5 Gy (group 3) from days 15 to 19 after induction (15 animals/group). On days 21 (n=12 joints/group) and 30 (n=18 joints/group), cryostat sections were analysed histologically and immunohistologically after specific staining for macrophages, iNOS, COX-2 and HO-1. RESULTS: A total of 5 x 1.0 Gy or 5 x 0.5 Gy led to a significant reduction of clinical symptoms from days 21 to 29, and a highly significant reduction of cartilage and bone destruction on day 30. Macrophage-positive areas could be detected continuously throughout the periarticular infiltrate, and were slightly reduced after LD-RT on days 21 and 30. This reduction was more pronounced after 5 x 1.0 Gy. Following LD-RT, the iNOS score was reduced by about 45-50% on days 21 (p<0.05) and 30 (p<0.001). In contrast, the HO-1 score was increased by about 50% on days 21 (p=0.08) and 30 (p=0.03). CONCLUSIONS: The clinically and histologically observed prevention of the progression of adjuvant arthritis after LD-RT given during the peak of the acute inflammatory response and the reduction of cartilage and bone destruction in the chronic phase appears to be related to the modulation of iNOS activity by low X-ray doses.
12865402 Osteopontin: a bridge between bone and the immune system. 2003 Jul The molecular mechanisms underlying the putative role of osteopontin in the chronic inflammatory disease rheumatoid arthritis are unclear. A study in a murine model of arthritis now demonstrates that a specific antibody directed against the exposed osteopontin epitope SLAYGLR is capable of preventing inflammatory cell infiltration in arthritic joints.
14998195 Acute severe reversible oligohydramnios induced by indomethacin in a patient with rheumato 2004 Although the association between oligohydramnios and indomethacin use for premature labor has been well known for many years, there have been few cases published about it. We present a case of indomethacin-induced oligohydramnios due to use in a patient for rheumatoid arthritis. A 27-year-old G2P1 woman was referred to our prenatal unit with oligohydramnios at 33 weeks of pregnancy. Ultrasonography revealed severe oligohydramnios with an amniotic fluid index of 0.9 cm. She gave a history of daily 150 mg indomethacin use for newly diagnosed rheumatoid arthritis. All possible reasons for oligohydramnios were excluded and indomethacin was discontinued. In four days the amniotic fluid was observed as normal. We concluded that the oligohydramnios caused by indomethacin occurs quickly, is dose-related and reversible. Amniotic fluid volume should be monitored while using indomethacin.
15515416 Serotonin type 3 receptor antagonist tropisetron in the treatment of chronic inflammatory 2004 Several lines of research indicate that serotonin (5-hydroxytryptamine, 5-HT) and 5-HT receptors may play a part in the pathogenesis of chronic inflammatory rheumatic conditions like rheumatoid arthritis (RA) and scleroderma/progressive systemic sclerosis (PSS). In this paper, case reports on two patients with RA who were successfully treated with 5-HT3 receptor antagonist tropisetron were presented. Short-term oral tropisetron (5-10 mg/d) induced either remission of RA or improvement in RA-related symptoms, which lasted for several weeks or months after the treatment was discontinued. Interestingly, tropisetron was effective in a patient with refractory rheumatoid vasculitis, which is a severe complication that requires high-dose glucocorticoids in most cases. The beneficial effect of 5-HT3 receptor antagonists in RA and PSS suggests that this class of drugs may have potential in the treatment of chronic inflammatory rheumatic conditions. Double blind, placebo-controlled studies are urgently needed to confirm the efficacy and tolerance of 5-HT3 receptor antagonists in larger cohorts of patients.
12115174 The relationship of serum infliximab concentrations to clinical improvement in rheumatoid 2002 Jun OBJECTIVE: To investigate the relationship between serum concentrations of infliximab, a monoclonal anti-tumor necrosis factor alpha antibody, and clinical improvement from infliximab therapy for rheumatoid arthritis (RA). METHODS: Multiple blood samples were obtained from each of 428 subjects with active RA who were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (ATTRACT [Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy]) evaluating the clinical efficacy and safety of infliximab therapy. Serum levels of infliximab were measured by enzyme-linked immunosorbent assay. Dose-response trends were analyzed using generalized logistic regression techniques. Pharmacokinetic modeling was used to predict the serum concentrations of infliximab after simulated infusions using doses and dosing intervals not evaluated in the trial. RESULTS: At week 54, 26% of the subjects receiving 3 mg/kg infliximab every 8 weeks had undetectable trough serum levels of infliximab, a significantly greater proportion than in the other 3 treatment groups (P < 0.001). Increased magnitude of American College of Rheumatology (ACR) response (measured by the ACR-N, a continuous measure of clinical improvement derived from the ACR 20% response criteria) and greater reduction from baseline in serum C-reactive protein level were both associated with higher trough serum concentrations of infliximab (P < 0.001), as was less progression of radiographic joint damage (P = 0.004), providing support for a dose-response relationship. Pharmacokinetic models predicted that decreasing the dosing interval from 8 weeks to 6 weeks would yield higher trough serum levels of infliximab than increasing the dose by 100 mg. CONCLUSION: These results suggest that some patients with RA may benefit from infliximab given at higher doses than 3 mg/kg or more frequently than every 8 weeks.
12581606 Hypoxia-induced upregulation of the glycolytic enzyme glucose-6-phosphate isomerase perpet 2003 Mar Intra-articular hypoxia in the inflamed rheumatoid joint is associated with increased cell proliferation, enhanced metabolism and compromised vascular perfusion. Recent clinical studies using direct measurements of hypoxia in rheumatoid joints have delineated up to 20% of soft tissue pO(2) readings as below 10mm Hg. Increased markers for glycolysis exist in rheumatoid synovial fluid and upregulation of tissue glycolytic enzymes occurs in a rat model of synovitis. Recent reports show arthritis is provoked by linked T and B cell lymphocyte recognition of the glycolytic enzyme glucose-6-phosphate isomerase (GPI). This suggests an unusual physiological feature of rheumatoid joints leads to autoimmune destruction. In this report I suggest that hypoxia, within the rheumatoid joint, leads to upregulation of the glycolytic enzyme GPI which in turn perpetuates rheumatoid arthritis.
12223101 The molecular mechanism of osteoclastogenesis in rheumatoid arthritis. 2002 Bone-resorbing osteoclasts are formed from hemopoietic cells of the monocyte-macrophage lineage under the control of bone-forming osteoblasts. We have cloned an osteoblast-derived factor essential for osteoclastogenesis, the receptor activator of NF-kappaB ligand (RANKL). Synovial fibroblasts and activated T lymphocytes from patients with rheumatoid arthritis also express RANKL, which appears to trigger bone destruction in rheumatoid arthritis as well. Recent studies have shown that T lymphocytes produce cytokines other than RANKL such as IL-17, granulocyte-macrophage colony-stimulating factor and IFN-gamma, which have powerful regulatory effects on osteoclastogenesis. The possible roles of RANKL and other cytokines produced by T lymphocytes in bone destruction are described.
12707579 The power of the third dimension: tissue architecture and autoimmunity in rheumatoid arthr 2003 May Lymphoid organs are the anatomic solution to the challenge of responding to minute amounts of antigen with powerful effector mechanisms. By arranging interacting cells in complex three-dimensional topographies lymphoid organs provide an optimal match between form and function. This principle is exploited in ectopic lymphoid structures that characteristically appear in rheumatoid synovitis. Synovial tissue T cells and B cells cooperate in different types of lymphoid organizations. Dendritic cell networks in the inflamed synovial membrane optimize antigen collection, storage, processing, and presentation. Synovial tissue cells participate in lymphocyte recruitment and the formation of tissue architectures that amplify immune responses. Recent data support the concept that the tissue organization in the rheumatoid joint fosters a breakdown in self-tolerance by promoting a phase transition from self-limited immune responses to self-perpetuating autoimmune responses.
15266060 Raised serum prolactin in rheumatoid arthritis: genuine or laboratory artefact? 2004 Oct OBJECTIVES: Serum prolactin concentrations have been reported as higher, similar or lower in patients with rheumatoid arthritis (RA) compared with control subjects. We investigated whether low biological activity macroprolactin (a prolactin antibody complex), which is detected variably in different prolactin immunoassays, could account for the discrepant total prolactin results reported in RA. METHODS: We compared serum total prolactin and free prolactin in 60 women with RA and 31 female controls. RESULTS: No subject had hyperprolactinaemia or macroprolactinaemia. Serum concentrations of total and free (monomeric) prolactin were higher (P<0.05) in women with RA [mean (s.d.), 225.6 (104.6) and 201.6 (95.4) mU/l respectively] compared with controls [175.0 (68.5) and 154.0 (60.9) mU/l respectively]. CONCLUSIONS: We report higher serum free prolactin concentrations in women with RA compared with control subjects. This result indicates that the higher serum total prolactin levels in patients with RA are the consequence of increased free prolactin concentrations and are not due to macroprolactin.
15146421 Proteomic surveillance of autoimmunity in osteoarthritis: identification of triosephosphat 2004 May OBJECTIVE: Autoimmunity to proteins, such as type II collagen and cartilage intermediate layer protein, that are produced by chondrocytes has been reported in patients with osteoarthritis (OA) as well as in patients with rheumatoid arthritis (RA). However, it remains to be determined whether the overall specificities of the autoimmunity differ between OA and RA patients. This study sought to clarify the differences by applying proteomic surveillance for the detection of autoantigens comprehensively. METHODS: Serum samples were obtained from 20 patients with OA, 20 patients with RA, and 20 healthy volunteers. Human chondrocyte proteins were separated from the sera by 2-dimensional electrophoresis, and antigenic protein spots were detected by Western blotting. The antigenic proteins were then identified by mass fingerprinting. The antigenicity of the identified proteins was confirmed and the prevalence of the autoantibodies in the OA, RA, and other disease groups was determined with the use of recombinant proteins. In addition, autoepitopes were mapped on the antigens. RESULTS: Nineteen protein spots were recognized only by the OA sera, but not by the RA sera. One of these proteins was identified as triosephosphate isomerase (TPI). IgG-type anti-TPI autoantibodies were detected in 24.7% of the serum samples and 24.1% of the synovial fluid samples from the patients with OA, whereas <6% of the RA and systemic lupus erythematosus samples were positive for anti-TPI. In addition, multiple autoepitopes were identified on TPI. CONCLUSION: The overall profile of autoimmunity in OA differs from that in RA, which may reflect the OA-specific pathologic role of autoimmunity. The autoantibody to TPI, detected predominantly in the OA samples and produced by the antigen-driven mechanism, has the potential to be used as a diagnostic marker for OA.
12810925 CARD15/NOD2 analysis in rheumatoid arthritis susceptibility. 2003 Nov OBJECTIVE: To determine if the mutations in the CARD15/NOD2 gene predisposing to Crohn's disease (CD) contribute also to the genetic susceptibility to rheumatoid arthritis (RA). METHODS: The frequencies of the three commonest mutations of CARD15/NOD2 predisposing to CD (2104C > T, 2722G>C and 3020insC) were determined in 210 RA patients and 227 controls. RESULTS: Allelic frequencies of the CARD15/NOD2 mutations in RA patients (2104C>T, 2.8%; 2722G>C, 0.9%; and 3020insC, 2.4%) did not differ significantly from the controls (2104C>T, 5.3%; 2722G>C, 0.7%; and 3020insC, 1.1%). CONCLUSION: There was no evidence of association between the commonest CD CARD15/NOD2 mutations and RA susceptibility.