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

ID PMID Title PublicationDate abstract
15370754 ICF Core Sets for rheumatoid arthritis. 2004 Jul OBJECTIVE: To report on the results of the consensus process integrating evidence from preliminary studies to develop the first version of a Comprehensive ICF Core Set and a Brief ICF Core Set for rheumatoid arthritis. METHODS: A formal decision-making and consensus process integrating evidence gathered from preliminary studies was followed. Preliminary studies included a Delphi exercise, a systematic review, and an empirical data collection. After training in the ICF, and based on these preliminary studies, relevant ICF categories were identified in a formal consensus process by international experts from different backgrounds. RESULTS: The preliminary studies identified a set of 530 ICF categories at the second, third and fourth ICF levels with 203 categories on body functions, 76 on body structures, 188 on activities and participation, and 63 on environmental factors. Seventeen experts from 12 different countries attended the consensus conference on rheumatoid arthritis (7 physicians with at least a specialization in physical and rehabilitation medicine, 7 rheumatologists, one nurse, one occupational therapist, and one physical therapist). Altogether 96 categories (76 second-level and 20 third-, and fourth-level categories) were included in the Comprehensive ICF Core Set with 25 categories from the component body functions, 18 from body structures, 32 from activities and participation, and 21 from environmental factors. The Brief ICF Core Set included a total of 39 second-level categories, with 8 on body functions, 7 on body structures, 14 on activities and participation, and 10 on environmental factors. CONCLUSION: A formal consensus process integrating evidence and expert opinion based on the ICF framework and classification led to the definition of ICF Core Sets for rheumatoid arthritis. Both the Comprehensive ICF Core Set and the Brief ICF Core Set were defined.
15353607 A new approach to studying angiogenesis in rheumatoid arthritis by means of power Doppler 2004 Dec OBJECTIVE: To evaluate angiogenesis as an essential component of pannus formation and cartilage destruction in rheumatoid arthritis (RA) using power Doppler ultrasonography (PDUS) and serum vascular endothelial growth factor (VEGF) measurement. METHODS: Twenty-one RA patients with a painful and swollen wrist and 12 healthy controls were examined with ultrasound. By means of standard scans, vascularity near and inside the joint capsule was visualized with PDUS. Two trained investigators performed sonography. Representative video clips were stored and read by two independent investigators, under blinded conditions, with regard to the microvascular Doppler flow being either inside or outside the joint capsule and with respect to a qualitative estimate of the intensity of blood flow, according to a grading from 1 to 3. Serum levels of VEGF were measured with a standard quantitative sandwich ELISA. RESULTS: The power Doppler mode identified increased synovial microvascular blood flow inside the joint capsule in 17 of 21 RA patients (81%) vs one of the healthy controls. We found large variation in serum VEGF levels in RA patients and in healthy controls. The degree of synovial vascularity determined by PDUS showed no correlation with the immediate serum VEGF level in the same patient. CONCLUSION: The high correlation between intra-articular microvascular power Doppler flow and clinical synovitis in RA patients (P<0.0001) indicates that PDUS may be helpful in studying the role of synovial blood vessels in rheumatoid inflammation.
12671494 Accuracy of spinal navigation for magerl screws. 2003 Apr The influence of a protocol of preoperative computed tomography scanning and a special registration technique was assessed on the accuracy of navigation for implanting Magerl C1-C2-screws. The use of navigation systems for implanting Magerl screws could help to decrease the risk of complications and to reduce the required skin incision. Two parameters conceivably affecting the accuracy are the protocol of preoperative computed tomography scanning and the registration technique. Four cervical spine segments of human cadavers were scanned with two computed tomography protocols. Registration was done based on anatomic landmarks or using a specially designed percutaneous registration device. For the accuracy check, the pointer tip was placed exactly on the markers. The displayed distance on the monitor was referred as an estimate of accuracy. Varying the computed tomography protocol did not significantly affect the accuracy. The mean accuracy was improved from 3 mm after anatomic pair-point matching to 1.5 mm after matching using the percutaneous registration device. The accuracy obtainable seems to be sufficient for implanting Magerl screws by using frameless stereotactic navigation. Three-millimeter slice thickness and 2-mm table increment is a proper protocol for preoperative computed tomography scanning. Fiducial markers improve the accuracy significantly.
15229943 Quantitation of metalloproteinase gene expression in rheumatoid and psoriatic arthritis sy 2004 Jul OBJECTIVE: The distinct and different patterns of radiological damage in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) may be a product of the relative balance of proteolytic enzyme and inhibitor gene expression in synovial tissue. This study compared metalloproteinase gene expression in synovium located proximal to the cartilage-pannus junction (CPJ) and distal to the CPJ (non-CPJ) in patients with PsA and RA. METHODS: Synovial biopsies were obtained from CPJ and non-CPJ sites under direct vision at arthroscopy of an inflamed knee in patients with PsA (n = 12) and RA (n = 12) who were not under disease modifying antirheumatic drug treatment. A competitive, quantitative RT-PCR technique was established for synovial RNA using a polycompetitor construct containing mRNA-specific primer sites for collagenase (MMP-1), stromelysin (MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1), and GAPDH. cDNA products were separated and quantified by ethidium bromide stained gel electrophoresis and mRNA values were normalized relative to GAPDH expression. RESULTS: MMP-1, MMP-3, and TIMP-1 mRNA were upregulated in RA and PsA synovium with a prodestructive (MMP-1 + MMP-3)/TIMP-1 balance in both diseases. Similar levels of MMP mRNA expression were observed in PsA and RA despite the presence of less radiological erosion in the PsA group. No difference was observed in the degree of upregulation of MMP-1, MMP-3, or TIMP-1 mRNA in paired biopsies from CPJ and non-CPJ sites in either PsA (n = 8) or RA (n = 10). The ratio of TIMP-1 expression in CPJ compared to non-CPJ biopsies was higher in patients with nonerosive disease (10.1 +/- 27.8) than in erosive patients (0.75 +/- 0.27; p = 0.07). CONCLUSION: PsA and RA have similar levels of MMP-1, MMP-3, and TIMP-1 mRNA expression in synovium. There is no evidence of increased metalloproteinase mRNA expression at the CPJ in RA or PsA. The different patterns of radiological progression seen in RA and PsA were not explained by differences in synovial mRNA expression of MMP-1, MMP-3, or TIMP-1.
15020333 The economic burden associated with osteoarthritis, rheumatoid arthritis, and hypertension 2004 Apr OBJECTIVE: To compare the economic burden to society incurred by patients with RA, OA, or high blood pressure (HBP) in Ontario, Canada. METHODS: Consecutive subjects recruited by 52 rheumatologists (RA) and 76 family physicians (OA and HBP) were interviewed at baseline and 3 months. Information was collected on demographics, health status, and any comorbidities. A detailed, open ended resource utilisation questionnaire inquired about the use of medical and non-medical resources and patient and care giver losses of time and related expenses. Annual costs were derived as recommended by national costing guidelines and converted to American dollars (year 2000). Statistical comparisons were made using ordinary least squares regression on raw and log transformed costs, and generalised linear modelling with adjustment for age, sex, educational attainment, and presence of comorbidities. RESULTS: Baseline and 3 month interviews were completed by 253/292 (86.6%) patients with RA and 473/585 (80.9%) patients with OA and/or HBP. Baseline and total annual disease costs for RA (n = 253), OA and HBP (n = 191), OA (n = 140), and HBP (n = 142), respectively, were $9300, $4900, $5700, and US$3900. Indirect costs related to RA were up to five times higher than indirect costs incurred by patients with OA or HBP, or both. The presence of comorbidities was associated with disease costs for all diagnoses, cancelling out potential effects of age or sex. CONCLUSION: The economic burden incurred by RA significantly exceeds that related to OA and HBP, while differences between patients with a diagnosis of OA without HBP or a diagnosis of HBP alone were non-significant, largely owing to the influence of comorbidities.
12607305 [An autopsy case of protein-losing enteropathy due to gastrointestinal amyloidosis, occurr 2002 Sep On August 14, 2001, a 76-year-old woman with a history of rheumatoid arthritis was admitted to our hospital with fever, cough, dyspnea and diarrhea. On admission, her chest radiography showed pleural effusion on the right side, and thoracocentesis was used to diagnose empyema. The patient underwent pleural drainage and received antibiotics. Alpha-Streptococcus was detected in both aerobic and anaerobic cultures of the pleural effusion. After 2 weeks of therapy, her empyema had improved; but her diarrhea, which had started 1 week before admission, had worsened, and her hypoproteinemia had progressed. Examination of the fecal clearance of alpha-1-antitrypsin and biopsied rectal material revealed that the diarrhea was caused by protein-losing enteropathy due to gastrointestinal amyloidosis secondary to rheumatoid arthritis. The patient was treated with steroids, but developed an additional infectious disease and died on September 29, 2001. In this case, she suffered from various infectious diseases including empyema and fungus infections. It has been reported that protein-losing enteropathy accompanies abnormalities in the immune system, by the loss of immunoglobulins and lymphocytes from the gut. We therefore suspect that protein-losing enteropathy due to gastrointestinal amyloidosis caused this patient's empyema.
12920694 Effectiveness of psoriatic arthritis therapies. 2003 Aug OBJECTIVE: To review the effectiveness of systemic therapies for psoriatic arthritis (PsA). METHODS: Data on the efficacy of PsA therapies from selected literature, including American and international medical journals and recent abstracts from key rheumatology meetings, were reviewed. RESULTS: Most therapeutic agents used to treat PsA are used on the basis of data from patients with rheumatoid arthritis (RA), and have not been adequately assessed in patients with PsA. However, the progressively destructive nature of the disease demands aggressive treatment with agents tested specifically in PsA. Conventional agents used to treat RA, such as methotrexate and sulfasalazine, have adverse effects that often lead to drug discontinuation and may not always be effective in reducing symptoms or radiographic progression in PsA. Newer medications, such as etanercept and infliximab, specifically inhibit the actions of tumor necrosis factor, which plays a major role in joint destruction. The Food and Drug Administration has recently approved etanercept for treatment of PsA. Current data with infliximab are limited to small open-label trials; however, randomized controlled trials are underway. CONCLUSIONS: PsA and RA are distinct diseases, and the efficacy and safety of an agent in RA cannot necessarily be equated with efficacy and safety in PsA. For most conventional agents, data from controlled clinical trials in PsA are scant. Etanercept is currently the only therapeutic agent with sufficient data from placebo-controlled, randomized trials to receive a Food and Drug Administration indication for the treatment of PsA.
12491140 [Essential cryoglobulinemic vasculitis with severe peripheral neuropathy and neurogenic mu 2002 Dec We report on a 60 year old patient with peripheral neuropathy, neurogenic muscular atrophy, skin ulcers, arthritis and weakness. Detection of cryoglobulins in association with typical clinical symptoms, exclusion of hepatitis C and any other disease led to a rare diagnosis: essential cryoglobulinemic vasculitis. The case demonstrates not only the difficult diagnostic process but also the problems of an adequate and effective therapy. Since the usual immunosuppressive treatments such as methotrexate, high dose corticosteroid and intermittent intravenous pulse cyclophosphamide therapy (Austin's scheme) failed, we performed plasmapheresis (cascade filtration), which brought about an immediate and long-term remission. Besides discussing various types of plasmapheresis procedures and potential pathophysiological mechanisms, we point out that this therapy could find an early use in severe essential cryoglobulinemic vasculitis because of its excellent risk/benefit ratio.
15552955 [Unanticipated endotracheal tube displacement in a short-neck patient with a history of ch 2004 Oct Endotracheal tubes are known to have a risk of being displaced at neck extension or flexion or rotation. However, the displacement seldom causes clinical problems. An 74-year-old patient suffering from chronic rheumatoid arthritis underwent debridement in the infected knee under general anesthesia. Mechanical ventilation had to be continued because of poor oxygenation after the operation. She had been intubated with Hi Lo Evac endotracheal tube (HLE) for 3 days, then extubated. However, she again needed mechanical ventilation because of aggravated oxygenation. At that time, Profile cuff siliconised endotracheal tube (PCS) was placed for 3 days. We encountered dangerous displacement of HLE during the first mechanical ventilation, but did not have any clinically dangerous displacement of PCS during the second mechanical ventilation. Therefore, we compared the hardness of the three popular endotracheal tubes. We found the hardness of HLE was higher than the others. This might be one of the reasons for dangerous displacement of the endotracheal tube in our case.
15593201 Development of autoimmune arthritis with aging via bystander T cell activation in the mous 2004 Dec OBJECTIVE: A wide spectrum of extraglandular manifestations may occur in patients with Sjogren's syndrome (SS), but the mechanisms responsible for in vivo progression are still obscure. We undertook this study to evaluate the age-related changes during the development of extraglandular autoimmune lesions, including arthritis, in the murine model of primary SS, and to evaluate the possible relationship between age-related disturbance of activation-induced cell death and the in vivo kinetics against autoantigens. METHODS: A total of 126 NFS/sld mice were investigated at ages 2, 4, 6, 10, 12, 18, 20, and 24 months. Cytokine production was tested using culture supernatants from anti-CD3 monoclonal antibody-stimulated T cells. Anti-single-stranded DNA (anti-ssDNA) antibodies, Ig isotypes (IgG1, IgG2a), rheumatoid factor (RF), and anti-type II collagen (anti-CII) antibodies were detected by enzyme-linked immunosorbent assay. Proliferative T cell responses against each of 3 recombinant alpha-fodrin proteins and against CII were analyzed. RESULTS: Autoimmune arthritis developed in SS model mice until age 24 months. Significant elevations in serum levels of RF, anti-ssDNA antibodies, and anti-CII antibodies were found in aging SS model mice. A high titer of serum autoantibodies against alpha-fodrin fragments (containing different epitopes that were originally identified in primary SS model mice) was frequently detected in young and aged SS model mice. Moreover, we found that alpha-fodrin autoantigen induced Th1 immune responses and accelerated disturbance of Fas-mediated T cell apoptosis in aged SS model mice. CONCLUSION: These results indicate that age-related disturbance of activation-induced cell death via bystander T cell activation may play a crucial role in the development of autoimmune arthritis in a murine model of SS.
12508772 Hyperprolactinaemia in patients with systemic lupus erythematosus. 2002 Nov OBJECTIVE: To verify the presence of hyper-PRL in SLE patients, its association with high disease activity, specific organ involvement or presence of anti-ds-DNA antibodies. METHODS: The group under study consisted of 80 patients with systemic lupus erythematosus (SLE), 28 patients with rheumatoid arthritis (RA) and 27 healthy controls. PRL serum levels were assayed using standard commercial kits (Immunotech Prague) with the radioimmunometric method for testing three samples of each of the subjects. The samples were taken in the morning hours (9-11 a.m.) of absolute rest 30 minutes after the introduction of the cannula at 30-minute intervals. RESULTS: A significantly higher rate of elevated PRL levels was found in SLE patients (40.0%) compared with the healthy controls (14.8%, p < 0.017). No proof was found of association with the presence of anti-ds-DNA or with specific organ involvement. Similarly, elevated PRL levels were found in RA patients (39.3%). The PRL elevation tended to decline from the 1st to the 3rd sample in the group of patients with SLE and RA but not in healthy controls. CONCLUSION: As follows from our measurements of prolactin serum values in SLE patients they are varriable by definition. According to our opinion further investigations are needed.
15182636 [Effects of total alkaloids of Tongbiling prescription on Th1 type cytokine expression in 2004 Jan AIM: To study the effects of total alkaloid of Tongbiling prescription(TBL) on Th1 type cytokine expression in T cells in order to elucidate the anti-inflammatory mechanism of TBL. METHODS: The lymphocytes were isolated from mouse mesenteric lymph nodes and cultured in-vitro. Various concentrations of TBL were added to the culture followed by phorbol ester and inomycin treatment and then incubated for another 4 hours. The expressions of IFN-gamma and TNF-alpha in the lymphocytes were analyzed by flow cytometry. RESULTS: 200 mg/L and 100 mg/L TBL could obviously inhibit IFN-gamma and TNF-alpha expressions in T lymphocytes. CONCLUSION: Inhibiting Th1 cytokine expression may be one mechanism by which TBL can treat rheumatoid arthritis.
14648481 [Functional duality of kinin receptors in pathophysiology]. 2003 Nov Kinins are autacoid peptides and central neuromediators involved in cardiovascular regulation, inflammation and pain. Their effects are mediated by two transmembrane G-protein-coupled receptors denoted as B1 and B2. While the B2 receptor is constitutive, the B1 receptor is inducible and up-regulated in the presence of cytokines, endotoxins or during tissue injury. The B2 receptor is believed to play an important role in the beneficial effects of angiotensin-1 converting enzyme inhibitors used in the treatment of cardiovascular diseases, yet it is involved in the acute phase of inflammation and of somatic and visceral pain. Conversely, the B1 receptor participates in the chronic phase of these responses and is likely to play a strategic role in diseases with a strong immune component such as rheumatoid arthritis, multiple sclerosis, septic shock and diabetes. A dual function for the B1 receptor is also reported in some pathologies in which it can exert either a protective (multiple sclerosis and septic shock) or harmful (pain and inflammation) effect. Therefore, the use of antagonists for these receptors as clinical therapeutic agents requires a rigorous evaluation of the potential side effects.
14634788 Myocardial infarction caused by rheumatoid vasculitis: histological evidence of the involv 2003 Nov Rheumatoid arthritis (RA) is a chronic joint disease that can be complicated with extra-articular manifestations due to vasculitis. We describe a patient with RA who developed systemic vasculitis and died of myocardial infarction. Autopsy demonstrated vasculitis of the left anterior descendent and circumflex coronary arteries, which were narrowed or occluded with organizing thrombosis. Formation of granuloma with multinucleated giant cells was also observed in media of the circumflex artery. There was no microscopic evidence of atheroma formation in the coronary arteries. Of note, there was a follicle-like infiltration of CD45RO-positive T lymphocytes in interna of the left coronary arteries and the right renal artery. Although not frequently reported, coronary vasculitis as a cause of myocardial infarction should be considered in patients with RA. Moreover, our results suggest that infiltration of T lymphocytes might be involved in the development of rheumatoid vasculitis.
15124024 The MHC class I-like Fc receptor promotes humorally mediated autoimmune disease. 2004 May The MHC class I family-like Fc receptor, FcRn, is normally responsible for extending the life span of serum IgG Ab's, but whether this molecule contributes to autoimmune pathogenesis remains speculative. To determine directly whether this function contributes to humoral autoimmune disease, we examined whether a deficiency in the FcRn heavy chain influences autoimmune arthritis in the K/BxN mouse model. FcRn deficiency conferred either partial or complete protection in the arthritogenic serum transfer and the more aggressive genetically determined K/BxN autoimmune arthritis models. The protective effects of an FcRn deficiency could be overridden with excessive amounts of pathogenic IgG Ab's. The therapeutic saturation of FcRn by high-dose intravenous IgG (IVIg) also ameliorated arthritis, directly implicating FcRn blockade as a significant mechanism of IVIg's anti-inflammatory action. The results suggest that FcRn is a potential therapeutic target that links the initiation and effector phases of humoral autoimmune disease.
14613263 Comparison of rheumatoid arthritis clinical trial outcome measures: a simulation study. 2003 Nov OBJECTIVE: Isolated studies have suggested that continuous measures of response may be better than predefined, dichotomous definitions (e.g., the American College of Rheumatology 20% improvement criteria [ACR20]) for discriminating between rheumatoid arthritis (RA) treatments. Our goal was to determine the statistical power of predefined dichotomous outcome measures (termed "a priori"), compared with that of continuous measures derived from trial data in which there was no predefined response threshold (termed "data driven"), and to evaluate the sensitivity to change of these measures in the context of different treatments and early versus later-stage disease. In order to generalize beyond results from a single trial, we performed simulation studies. METHODS: We obtained summary data from trials comparing disease-modifying antirheumatic drugs (DMARDs) and from comparative coxib-placebo trials to test the power of 2 a priori outcomes, the ACR20 and improvement of the Disease Activity Score (DDAS), as well as 2 data-driven outcomes. We studied patients with early RA and those with later-stage RA (duration of <4 years and 4-9 years, respectively). We performed simulation studies, using the interrelationship of ACR core set measures in the trials to generate multiple trial data sets consistent with the original data. RESULTS: The data-driven outcomes had greater power than did the a priori measures. The DMARD comparison was more powerful in early disease than in later-stage disease (the sample sizes needed to achieve 80% power for the most powerful test were 64 for early disease versus 100 for later disease), but the coxib-versus-placebo comparison was less powerful in early disease than in later disease (the sample sizes needed to achieve 80% power were 200 and 100, respectively). When the effects of treatment on core set items were small and/or inconsistent, power was reduced, particularly for a less broadly based outcome (e.g., DDAS) compared with the ACR20. CONCLUSION: The simulation studies demonstrate that data-driven outcome definitions can provide better sensitivity to change than does the ACR20 or DDAS. Using such methods would improve power, but at the expense of trial standardization. The studies also show how patient population and treatment characteristics affect the power of specific outcome measures in RA clinical trials, and provide quantification of those effects.
15093759 Effects of rofecoxib and naproxen on life expectancy among patients with rheumatoid arthri 2004 May 1 BACKGROUND: The VIOXX Gastrointestinal Outcomes Research (VIGOR) trial showed a 53% decrease in the risk of upper gastrointestinal toxicity and a fivefold increase in the risk of myocardial infarction for rofecoxib (a selective cyclooxygenase-2 inhibitor) compared with naproxen. We examined the effects of these competing adverse events on life expectancy in patients with rheumatoid arthritis. METHODS: We used decision analysis to compare the life expectancy of a cohort of rheumatoid arthritis patients taking naproxen versus a similar cohort taking rofecoxib, using data from the VIGOR trial. We incorporated the competing risks of upper gastrointestinal toxicity and myocardial infarction, as well as their long-term health consequences, on the basis of population-based studies. RESULTS: For 58-year-old women with rheumatoid arthritis (i.e., typical of participants in the VIGOR trial), naproxen was associated with a longer life expectancy than was rofecoxib (difference = 4.4 months). This difference was larger among 58-year-old men (7.8 months). The probability that naproxen is associated with a longer life expectancy than rofecoxib among 58-year-old patients was 92% for women and 98% for men. Life expectancy became the same between the two treatments when the risk of upper gastrointestinal toxicity was 70% higher or the risk of myocardial infarction was 40% lower than that of the base case among women, and when the risk of upper gastrointestinal toxicity was 4.4-fold higher or the risk of myocardial infarction was 70% lower among men. CONCLUSION: Our analysis suggests that the competing risks of upper gastrointestinal toxicity and myocardial infarction shown in the VIGOR trial would project a longer life expectancy with naproxen than rofecoxib among patients with rheumatoid arthritis, except in those at low risk of myocardial infarction or at high risk of upper gastrointestinal toxicity.
11863229 Guidelines for the laboratory use of autoantibody tests in the diagnosis and monitoring of 2002 Feb The Italian Society of Laboratory Medicine Study Group on the Diagnosis of Autoimmune Diseases has generated a series of guidelines for the laboratory diagnosis and monitoring of systemic autoimmune rheumatic diseases intendedfor the use of clinical pathologists and laboratory physicians. These guidelines are based on a systematic review of published works and expert panel discussion and consist of 13 recommendations for antinuclear antibodies, anti-double-stranded native DNA, and antinuclear specific antibodies. To improve analytic performances and help select the most appropriate test for specific autoantibodies, as well as provide education and guidance in the use of these tests, special emphasis is placed on laboratory methods.
14611807 Two-loci interaction confirms arthritis-regulating quantitative trait locus on rat chromos 2003 Dec A form of genetic interaction, or epistasis, occurs when one gene interferes with the phenotypic effect of another nonallelic gene. In pristane-induced arthritis (PIA) in rats we have previously identified Pia3, on chromosome 6, to be a locus that regulates onset of disease. In a single congenic strain containing Pia3 on the arthritis-susceptible DA background, DA.Pia3, no difference in onset of disease or early disease severity could be detected. After a two-loci interaction analysis of (E3 x DA)F2 intercross data, Pia3 was found to interact with Pia4 (chromosome 12). Subsequently, the DA.Pia3 congenic strain was combined with the DA.Pia4 congenic strain so that an effect of Pia3 could be observed. The effect of heterozygosity in Pia4 results in lower severity and thus in combination with Pia3 made it possible to observe that Pia3 alleles from the arthritis-resistant E3 strain rendered more severe arthritis into the otherwise 100% susceptible DA strain. As the introduction of Pia4 heterozygosity results in a lower level of arthritis severity we regard this as an additive interaction with a severity threshold-lowering effect.
12051398 Mononuclear cell response to enterobacteria and Gram-positive cell walls of normal intesti 2002 Mar OBJECTIVE: To study whether enterobacteria and Gram-positive bacterial cell walls (BCW) derivedfrom normal intestinal microbiota are involved in the etiopathogenesis of early rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were isolatedfrom patients with early RA (the average duration of 5 months) and the controls (other types of inflammatory arthritis). The mononuclear cell proliferation and tumor necrosis factor-alpha (TNF-alpha) responses to heat-killed Salmonella enteritidis (SE). Yersinia enterocolitica (YE), and Escherichia coli (EC), and to Gram-positive BCW derived from four common intestinal indigenous bacteria, Eubacterium aerofaciens (EA), Eubacterium limosum (EL), Lactobacillus casei (LC), and Lactobacillus fermentum (LF), and a BCW derived from a pathogen, Streptococcus pyogenes (SP) were investigated. RESULTS: 39% or 56% of patients with early RA showed significant proliferation responses by PBMC or SFMC against enterobacteria, respectively. In other types of arthritis, corresponding figures were 59% or 66%. When BCW were used as antigens, 8.1% or 23% of patients with early RA showed proliferation responses by PBMC or SFMC, respectively. In other types of arthritis the corresponding figures were 7.5% or 35%, respectively. However, TNF-alpha production by SFMC stimulated by EA BCW, SE, YE or EC, was significantly higher in early RA than in other types of arthritis. CONCLUSION: These results suggest that SFMC reacting with enterobacteria or BCW exist in some patients with early RA, but also in other types of inflammatory arthritis. Intestinal bacterial agents may play a role in the etiopathogenesis of RA, but the effect appears to be non-specific.