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ID PMID Title PublicationDate abstract
8876772 Psychoneuroimmunology of autoimmune disorders. 1996 The interactions between the immune system and psychological states are both intricate and intriguing. Research at a molecular level has thrown considerable light on the previously ill-defined area of psychoneuroimmunology. In this report, we explore the psychoneuroimmunology of autoimmune disorders, particularly rheumatoid arthritis and lupus erythematosus. Animal models of these diseases have provided a particularly useful window on complex psychoneuroimmunological interactions. Observations about the effect of stress on the onset and course of autoimmune disorders has added to our understanding of psychoneuroimmunological interactions. These interactions are bi-directional, as reflected in the autoimmune-mediated neuropsychiatric manifestations of systemic lupus. Exploring the role of various neurotransmitters and neuromodulators in the stress response may have important therapeutic implications for autoimmune disorders.
9014583 Annexin V autoantibodies in rheumatoid arthritis. 1996 Dec OBJECTIVE: To investigate the occurrence of anti-annexin V autoantibodies in sera of patients with rheumatoid arthritis to assess involvement with the disease and any relation to glucocorticoid treatment. METHODS: Anti-annexin V antibodies were measured by an enzyme linked immunosorbent assay (ELISA) which used the purified human recombinant protein as antigen. RESULTS: Concentrations of anti-annexin V autoantibodies, predominantly of the IgG class, were significantly raised in sera from patients with rheumatoid arthritis compared to normal controls. This was not correlated with other indices of disease activity such as erythrocyte sedimentation rate or C reactive protein and was unrelated to glucocorticoid treatment. CONCLUSIONS: Extracellular annexin V provides an antigenic stimulus for autoantibody production and its in vivo expression is independent of glucocorticoid control. Such autoantibodies may have a detrimental role in the arthritic condition by interfering with putative functions of annexin V, including collagen type II binding, inhibition of phospholipase A2 activity, and Fc receptor activity.
1583890 Development and application of a radioimmunoassay for interleukin-8: detection of interleu 1992 Apr A sensitive and specific radioimmunoassay for human interleukin-8 (IL-8) was developed using isotopically labeled homogenous natural protein. The detection limit (20% inhibition of 125I-IL-8 binding) was 30 pg/100 microliters; 50% displacement occurred at 140 pg/100 microliters. There was no cross-reactivity with the structurally and functionally related neutrophil-activating peptides 2 and 3 up to 500 ng/100 microliters. The intra- and inter-assay coefficients of variation were 4 and 7%, respectively. In vitro experiments showed that human fibroblasts triggered by interleukin-1, double-stranded RNA or virus release immunoreactive and biologically active IL-8 in a dose- and time-dependent manner. Monocytes produce immunoreactive IL-8 in the 100 ng/ml range when exposed to plant mitogen, bacterial endotoxin, virus or IL-1. Although the radioimmunoassay was more sensitive than the chemotaxis assay (detection limit 0.6 ng/ml versus 10 ng/ml) a correlation between concentrations of immunoreactive IL-8 and neutrophil chemotactic activity in the supernatants from stimulated monocytes and fibroblasts was observed. In synovial fluids from patients with inflammatory joint disease, IL-8 was clearly demonstrable, but there was no correlation between IL-8 levels and general parameters of disease activity (erythrocyte sedimentation rate and serum levels of C-reactive protein). Synovial fluids from patients with rheumatoid arthritis, seropositive for rheumatoid factor, contained significantly higher concentrations of IL-8 than synovial fluids from seronegative rheumatoid arthritis patients and patients with non-rheumatoid arthritis joint inflammation. There was a highly significant correlation between IL-8 levels and serum titers of rheumatoid factor. These findings suggest that the molecular mechanisms underlying joint inflammation may be distinct in different types of arthritis.
1377997 Allotype-dependent stimulation of peripheral blood and synovial lymphocytes by IgG3 in rhe 1992 Jun The immunopathologic process of rheumatoid arthritis (RA) is primarily expressed in the synovium where rheumatoid factor (RF) synthesis is concentrated. We hypothesized that RF synthesized by rheumatoid synovial cells (RSC) may be driven via a T cell-mediated immune response developed against IgG3 epitopes. To identify and characterize specific RSC RF epitopes and T cell antigens, two 28 amino acid peptides homologous with the C-terminus of IgG1 (P1) and IgG3 [G3m(5)] (P3) were synthesized and used in RF-binding studies and lymphocyte proliferation assays. Our results indicate that (i) the C-terminus of the CH3 domain contains epitopes for IgG3-reactive RSC RF; (ii) IgG3-reactive RSC RF binds primarily to IgG3 [G3m(5)]; (iii) P3 stimulated proliferation of T lymphocytes from both RA peripheral blood and RSC; and (iv) RF production was enhanced by P3 in selected RA cell cultures. These observations suggest that the C-terminus of IgG3 allotype G3m(5) may be important in T cell activation and RF production in RA.
8871836 Low serum hyaluronan in psoriatic arthritis patients in comparison to rheumatoid arthritis 1996 Jul OBJECTIVE: Serum hyaluronan (HA) was determined in 37 patients suffering from psoriatic arthritis (PSA), 39 patients with rheumatoid arthritis (RA), 31 with osteoarthritic joint disease (OA) and 26 healthy controls (C) in order to examine earlier reports that HA levels are increased in the serum of RA and to assess whether this finding is also relevant for PSA, another inflammatory joint disease, since HA in serum is considered a sign of inflammation in general. METHOD: HA in the serum samples was measured with an enzyme linked microplate assay. RESULTS: Sera from PSA, RA and OA patients showed a significantly higher HA concentration than those of healthy controls (56.0 +/- 16.0 micrograms/l). The serum HA concentration in PSA patients amounted to 107.8 +/- 57.2 micrograms/l, which was not significantly different from OA patients (104.9 +/- 16 micrograms/l). A significant difference, however, could be observed between the HA concentrations of the PSA subgroups: the mean HA level of patients suffering from symmetrical polyarthritis was 134 +/- 79.6 micrograms/l, which turned out to be significantly higher than in patients suffering from symmetrical oligoarthritis (89.9 +/- 42.8 micrograms/l; P < 0.04), but was insignificantly increased in comparison to patients with ankylosing spondylitis as the predominant feature (109 +/- 27.8 micrograms/l; P = 0.49). The mean HA concentration for RA sera was 197.1 +/- 122.9 micrograms/l, which was statistically significantly increased compared to PSA (P < 0.001) and OA (P < 0.001) sera. The sera of seropositive RA patients showed significantly higher HA levels than PSA patients with symmetrical polyarthritis (P < 0.04). CONCLUSION: The data obtained support recent studies which have shown HA levels to be higher in RA patients than in OA patients. Seronegative and seropositive RA patients showed the same HA concentrations, while patients suffering from "seronegative" PSA were found to have lower HA concentrations. Therefore, HA serum levels may reflect cartilage degradation in general or the degree of articular inflammatory processes, indicating different pathogenetic pathways.
7639808 Usefulness of the American College of Rheumatology recommendations for liver biopsy in met 1995 Aug OBJECTIVE: To test the usefulness and cost savings resulting from application of the new American College of Rheumatology (ACR) guidelines for assessing the risk for the development of clinically significant liver disease in rheumatoid arthritis (RA) patients treated with methotrexate (MTX). METHODS: One-hundred twelve MTX-treated RA patients were prospectively followed up for MTX hepatotoxicity and underwent liver biopsies according to modified guidelines of the Psoriatic Task Force (PTF). All biopsies were graded according to the Roenigk classification. The new ACR recommendations were then retrospectively applied to test their usefulness and cost-effectiveness in this cohort. RESULTS: Based on the PTF guidelines, 66 patients underwent liver biopsies; a total of 110 liver biopsies were performed. Two patients had biopsy-related complications. Five patients were found to have Roenigk grade IIIB or IV histologic abnormalities. The total cost for this group was $111,380. Applying the new ACR criteria, only 15 patients would have undergone liver biopsies; there would have been a total of 18 biopsies, with no complications. Four of the 5 patients with Roenigk grade IIIB or IV liver abnormalities would have been identified. One patient with insulin-dependent diabetes mellitus (IDDM) who was found to have cirrhosis (Roenigk grade IV) on liver biopsy as a result of use of the PTF guidelines would have been missed with use of the ACR guidelines. The total cost for the group receiving biopsies based on the ACR guidelines would have been $16,956. Overall, the new ACR guidelines had 80% sensitivity and 82% specificity and resulted in a cost savings of $1,430 per patient. CONCLUSION: The new ACR guidelines on MTX monitoring and biopsy surveillance appear to be clinically useful and result in considerable cost savings. However, 1 IDDM patient with significant liver histologic abnormalities would have been missed. We suggest that IDDM be added to the ACR guidelines as a risk factor for MTX hepatotoxicity.
7691662 A comparative evaluation of the metabolic profiles of normal and inflammatory knee-joint s 1993 Oct 18 High resolution 1H NMR spectroscopy has been employed to investigate the metabolic profile of healthy human knee-joint synovial fluid (SF) and the biochemical data acquired have been compared with those of matched serum, and inflammatory knee-joint SF samples. Results obtained indicate that the healthy human knee-joint has a hypoxic status (high lactate level when expressed relative to that of paired serum) that is milder than that of the inflamed human knee-joint. Moreover, normal SF differs from that of inflammatory SF in that it contains little or no NMR-detectable lipoprotein-associated fatty acids and 'acute-phase' glycoproteins, an observation reflecting the limited passage of these macromolecules from plasma into the synovial space in healthy subjects.
1539124 [Quantification of mRNA using the polymerase chain reaction--cytokines in rheumatoid arthr 1992 Feb 15 A method for quantitation of specific mRNA species by the polymerase chain reaction (PCR) has been developed by using a synthetic RNA as an internal standard. The specific target mRNA and the internal standard are co-amplified in one reaction in which the same primers are used. The amount of mRNA is then quantitated by extrapolating against the standard curve generated with the internal standard. The synthetic internal standard RNA consists of a linear array of the sequence of upstream primers of multiple target genes followed by the complementary sequences to their downstream primers in the same order. This quantitative PCR method provides a rapid method of quantifying the amount of a specific mRNA in a sample of less than 0.1 ng of total RNA. In addition, the same internal standard RNA is used, with appropriate primer pairs, to quantitate multiple different mRNA species in parallel. This technique affords a very sensitive means of measuring important regulatory cytokines in the local inflammatory tissue of rheumatoid arthritis (RA).
7725067 The identification of germinal centres and follicular dendritic cell networks in rheumatoi 1995 May We document here the identification of germinal centres with dark and light zones, a follicular dendritic cell network and clonal expansion in the synovium of rheumatoid arthritis patients. Synovial tissue from 24 patients suffering from rheumatoid arthritis or the polyarticular form of juvenile rheumatoid arthritis were screened for the presence of lymphoid follicles. The synovial tissues of 14 patients contained follicles and four of these had germinal centres and a follicular dendritic cell network. There was a statistically significant association between follicles in the synovium and the presence of rheumatoid factor autoantibodies in the patients' serum indicating a link between local germinal centre formation and the presence of pathological rheumatoid factors. Nucleotide sequencing of monoclonal rheumatoid factors from one of the patients' synovial tissue which contained germinal centres clearly supports the possibility that these rheumatoid factors have gone through a germinal centre reaction. While rheumatoid factors from healthy immunized donors are regulated through a tolerization mechanism which selects against replacement mutations and does not allow affinity maturation, synovial rheumatoid factors seem to lack this tolerization mechanism. The formation of germinal centres where B cells affinity mature and expand at the central site of disease in rheumatoid arthritis may explain why rheumatoid factors in rheumatoid arthritis develop into auto-aggressive antibodies.
8670318 Association of tumor necrosis factor microsatellite polymorphisms with HLA-DRB1*04-bearing 1996 Jul OBJECTIVE: To investigate 1) tumor necrosis factor (TNF) microsatellite allele frequencies in rheumatoid arthritis (RA), and 2) associations between TNF microsatellites and RA-associated HLA specificities in order to build up extended HLA haplotypes. METHODS: Eighty-five caucasoid patients with RA and 109 healthy caucasoid controls were typed for TNF microsatellites a-d using fluorescent-labeled primers and semiautomated genotyping. A further 56 RA patients who were selected for having certain HLA-DRB1 types were also typed for these TNF microsatellites. Linkage disequilibria between TNF and HLA alleles were calculated, and extended haplotypes were established. RESULTS: The TNFa6 allele frequency was significantly increased in the RA patients compared with the controls (P = 0.0019, odds ratio [OR] 2.5, 95% confidence interval [95% CI] 1.3-4.6), an increase that was further evident in patients who were HLA-DRB1*0401 homozygous (P = 0.0003, OR 7.3, 95% CI 2.2-24.4). This increase was found to be due to association with HLA-DRB1*0401. No TNF microsatellite allele was found to be associated with HLA-DRB1*0404. Three HLA extended haplotypes were identified in the RA group: 1) HLA-DRB1*0401;TNFd4;TNFa6;TNFb5;HLA-B44; HLA-Cw5;HLA-A2, 2) HLA-DRB1*0301;TNFd2; TNFa2;TNFb3;HLA-B8;HLA-Cw7;HLA-A1, and 3) TNFd5;TNFc2;TNFa2;TNFb1;HLA-B62;HLA-Cw3. CONCLUSION: TNF microsatellites found to be associated with RA do not appear to be independent of class II HLA associations.
1418016 Evidence for the presence of androgen receptors in the synovial tissue of rheumatoid arthr 1992 Sep OBJECTIVE: To study the presence of androgen receptors in the synovial tissue of male and female patients with rheumatoid arthritis (RA) and matched healthy controls. METHODS: Both site I (high affinity, low binding capacity) and site II (reduced affinity, higher binding capacity) androgen receptors were investigated in soluble and nuclear fractions of homogenized synovial samples, using the dextran-coated charcoal method. The finding of pure, high-affinity site I receptors in both fractions was considered indicative of androgen receptor positivity. In order to determine what type of synovial cell was positive for androgen receptors, cryosections of synovial tissues were immunostained with a specific monoclonal anti-androgen receptor antibody (MAb), using both immunofluorescence and immunoperoxidase techniques. Double immunostaining with this MAb and specific MAb directed toward different macrophage/granulocyte antigens was also performed. RESULTS: Remarkable differences were found between male and female controls: Most males were positive for androgen receptors, and most females were negative. The fetomolar content of androgen receptor in the nuclear fraction was fairly constant, but the soluble fraction showed a higher femtomolar concentration in female RA patients than in controls of either sex, as well as in male RA patients compared with female RA patients. The androgen receptor-positive cells in both RA and control synovial cryosections were found by immunostaining to be macrophage-like synoviocytes, and were also found to be HLA-DR positive. CONCLUSIONS: The immunosuppressive action exerted by androgens might, at least in part, be mediated through their interaction with macrophage-like synoviocytes functioning as antigen-processing and antigen-presenting cells in rheumatoid synovia.
8842724 An approach to complex rheumatoid hand and wrist problems. 1996 Aug Successful surgical reconstruction of the hands in patients with rheumatoid arthritis depends upon knowledge of the pathophysiology of the deformities and available surgical options, the use of appropriate operative and rehabilitative techniques, and, perhaps most importantly, a well-considered strategy for indicating and performing surgical procedures. In the case of complex hand deformities, two general approaches have guided the development of operative strategies. The first and most widely used strategy generally has involved sequential procedures. A less widely used but highly effective strategy uses multiple, concurrent procedures. Although it can be argued that both strategies are comprehensive, they are distinctly different. This article explores and defines the multiple, concurrent operations strategy and presents indications for and examples of its application. In contrast to sequential operations, in comprehensive reconstruction, all operations are done concurrently, providing that specific criteria are satisfied. When appropriately indicated by a hand surgeon experienced in all the technical components, a comprehensive strategy of rheumatoid hand reconstruction using multiple, concurrent operations can be highly effective. The strategy can provide restoration of patients' function and improve the quality of their life without compromising the results of any one component of the operation.
7562790 Interactive conference voting. The OMERACT II Committee. Outcome Measures in Rheumatoid Ar 1995 Jul We describe and analyze opinion polling results from interactive voting procedures undertaken before and after presentations during the Outcome Measures in Rheumatoid Arthritis Clinical Trials Conference (OMERACT II) in Ottawa, Canada, June 30-July 2, 1994. The scoring procedure was a matched voting design; when a participant used the same keypad at the beginning and end of voting, change within a participant could be estimated. Participants, experienced in the rheumatic diseases included clinicians, researchers, methodologists, regulators, and representatives of the pharmaceutical industry. Patients under consideration were those with any rheumatic diseases. Questions were constructed to evaluate the change in voting behavior expected from the content of the presentation. Statistically significant and substantively important changes were evident in most questions.
1588742 [Development of new drugs for the treatment of rheumatoid arthritis]. 1992 Mar Development of new drugs for the treatment of rheumatoid arthritis (RA) can be classified into two categories: one is modification and improvement of the drugs being used now and the other is development of more effective drugs which are being developed by virtue of progress in immunology and molecular biology. The author describes the present status of the treatment of RA and its future trend: anti-rheumatic and anti-inflammatory drugs which may be developed in the near future, recent progress in prodrugs of NSAID, cytokine antagonists, particularly for IL-1, and more specific immunological approaches to the treatment of RA. It is hoped that these potential anti-rheumatic drugs will be developed in next the 10-20 years.
1730105 Treatment of fixed flexion deformities of the knee in rheumatoid arthritis using the Flowt 1992 Jan Thirty established fixed flexion deformities of the knee in 18 rheumatoid arthritis patients were studied prospectively to assess the results of 8 weeks of out-patient treatment using the Flowtron intermittent compression stocking. A 44% mean correction of the fixed flexion deformity was obtained from an initial mean of 29 +/- 1 degrees to 16 +/- 1 degrees (P less than 0.001). More than 85% of this correction was obtained in the first 4 weeks of treatment. There was a significant correlation between the correction obtained and the inflation pressure (P less than 0.05), but the time of daily use (minimum 60 min) was not a significant factor. The modified Stanford Health Assessment Disability Index fell from an initial mean of 2.17 to 2.03 (P less than 0.01).
8759491 Duodenal mucosal ferritin in rheumatoid arthritis: implications for anaemia of chronic dis 1996 Jul Anaemia is a common feature of rheumatoid arthritis (RA) and other chronic diseases. Among the alterations in iron metabolism contributing to this effect is a decrease in intestinal iron absorption. The mechanism for this is unknown, but might involve a 'mucosal block' process similar to that proposed in iron overload, whereby increased expression of an enterocyte storage protein binds absorbed iron and prevents its transfer to the circulation. We examined the effect of disease-modifying therapy on ferritin expression in duodenal mucosa in RA to determine whether it may play a role in the 'mucosal block' process. Endoscopic small bowel biopsies were obtained from 11 patients with active RA both before, and 6 months after, a course of either gold or methotrexate (MTX). Mucosal ferritin levels in small bowel and stomach were measured by radioimmune assay. Duodenal mucosal ferritin decreased significantly following treatment (p < 0.05). There were no changes in gastric mucosal ferritin. The fall in duodenal mucosal ferritin correlated with indices of disease activity at start of therapy, and the largest decreases were in those patients showing the best response to treatment in terms of a fall in inflammatory markers. Site-specific changes in mucosal ferritin may underlie the altered iron absorption observed in active inflammatory disease by modifying the enterocyte 'mucosal block'.
9395559 Excess admixture proportion of extended major histocompatability complex haplotypes of Cau 1996 May Several extended major histocompatability complex (MHC) haplotypes are associated with susceptibility to autoimmune disease in Caucasian populations. It is known that African Americans and Afro-Caribbeans are ethnic groups descended from west, central and southern black African populations which are admixed with Caucasians. To examine the possible association of some marker of Caucasian MHC genes and susceptibility to rheumatoid arthritis (RA) in African Americans, we studied extended MHC haplotypes (HLA-B, complement and DR) in a sample of 18 African American and Afro-Caribbean probands with RA, their first degree relatives and in 15 non-RA families. We defined 36 disease-associated RA haplotypes among the probands and 96 normal haplotypes in normal individuals. To obtain the most conservative estimate, we excluded recognized Caucasian, DR4-bearing, extended MHC haplotypes from the analysis. Admixture proportions for non-HLA-DR4 extended MHC haplotypes of known Caucasian origin among RA-associated and normal haplotypes were computed (0.40 versus 0.163 respectively). When we compared the difference in proportions between RA and normal haplotypes, the proportion of extended MHC haplotypes of known Caucasian origin was significantly increased among RA-associated haplotypes (Z = 3.16, p (one sided) < 0.001, p (adjusted) < 0.008). Our results suggest that racial admixture with Caucasian MHC genes may augment RA susceptibility and thus may be one mechanism to explain the higher prevalence of RA in African Americans and Afro-Caribbeans than in black African populations.
8369888 Transient decrease in osteocalcin and markers of type 1 collagen turnover during high-dose 1993 Sep The effect of corticosteroid pulse therapy on bone metabolism was studied in 10 patients with active RA. We measured alkaline phosphatase, osteocalcin and two recently introduced markers of collagen type 1 metabolism, reflecting synthesis (PICP) and degradation (ICTP). The day after the pulse therapy, there was a statistically significant (P < 0.05) decrease in osteocalcin, PICP and ICTP from the value at start. Three weeks after pulse therapy, these values had returned to baseline. During pulse treatment there is a transient decrease in bone formation, as shown by the changes in osteocalcin and PICP. Because of the changes in ICTP, we conclude that bone resorption is transiently reduced as well, but whether these changes result from a direct or an indirect effect on bone is not clear. ICTP has to be investigated further as a (serum) marker of bone resorption.
8666867 [Open heart surgery in patients with systemic diseases requiring steroid treatment]. 1996 Apr Our surgical experiences in 9 patients who required steroid treatment for systemic diseases before, during and after the open heart surgery were reviewed. Subjects included 3 patients with systemic lupus erythematodes, 3 with aortitis syndrome, 1 with Behçet disease and 1 with rheumatoid arthritis. Cardiovascular lesion was aortic valve regurgitation in 2, Stanford A aortic dissection in 1 and ischemic heart disease in 3 patients. Duration of morbidity for systemic diseases before the surgery ranged between 0 nd 102 months, with a mean of 36 months. Steroid treatment was continued for 4 to 216 months (mean 70+/-76 months) before the surgery at a dose of 5-40 mg per day for conversion into prednisolone. In principal, methylprednisolone was given during the surgery, and the prednisolone was given at a dose of 20-140 mg per day on the day of operation or on the first postoperative day. Surgical procedures included a aortic valve prosthesis with Dacron cloth skirt implantation in 1 patient, surgical angioplasty of the left main coronary ostium in 1 and internal thoracic arteries grafting in 2 patients. Hospital mortality was 1 patient due to low cardiac output syndrome. Acute renal failure occurred in 2 patients with systemic lupus erythematodes, and wound complication was observed in 2 patients. In our experience, appropriate treatment for systemic diseases, timing of surgery and continuation of steroid treatment at an appropriate dose during and after the surgery seemed very important such as surgical procedure in order to prevent postoperative complications such as periprosthetic leakage and failure of anastomosis.
8182625 Effect of etodolac on methotrexate pharmacokinetics in patients with rheumatoid arthritis. 1994 Feb OBJECTIVE: To determine if the pharmacokinetics of methotrexate (MTX) is modified by the coadministration of etodolac. METHODS: MTX (10 mg) was administered intramuscularly in the absence and presence of steady state levels of etodolac in 19 patients with rheumatoid arthritis. MTX levels were assayed by fluorescence polarization immunoassay. Concentrations of 7-hydroxymethotrexate (7-OH-MTX) were assayed by a reverse phase high performance liquid chromatography method. The unbound fraction was determined by ultrafiltration. RESULTS: When etodolac was coadministered with MTX, the highest observed concentration decreased and the mean residence time increased to become statistically significant. However, these differences are not of great clinical importance especially given that the area under the curve and clearances were unchanged. There were no significant differences in binding protein and 7-OH-MTX concentrations between MTX with and without etodolac administration. CONCLUSION: The pharmacokinetics of MTX is slightly modified by coadministration of etodolac. Moreover, no clinical toxicity was observed.