Browse

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

ID PMID Title PublicationDate abstract
11899234 Regulation of apoptosis and cell cycle activity in rheumatoid arthritis. 2001 Nov The regulation of proliferation and cell death is vital for homeostasis, but the mechanisms that coordinately balances these two events in rheumatoid arthritis (RA) remains largely unknown. In RA, the synovial lining increases through enhanced proliferation, migration, and/or decreased cell death. The aberrant decrease in apoptosis or increased cell cycle activity of fibroblast-like or macrophage-like synoviocytes is responsible for the synovial hyperplasia and contributes to the destruction of cartilage and bone. Recently, numerous molecules that modulate apoptosis and cell cycle have been implicated to play a role in RA. This review will describe the current understanding of the molecular mechanisms that govern apoptosis and cell cycle and their relationship to RA pathogenesis.
11528522 Presence of four major haplotypes in human BCMA gene: lack of association with systemic lu 2001 Aug BCMA (TNFRSF17), along with TACI, has recently been demonstrated to be a receptor for BLyS (TNFSF13B). Recent studies indicated substantial role of BLyS signaling pathway for systemic lupus erythematosus (SLE). In the present study, we made an attempt to screen for polymorphisms of human BCMA, and to test their possible association with SLE and rheumatoid arthritis (RA). Two single nucleotide polymorphisms (SNPs) were detected within the coding sequence, both of which were synonymous substitutions. In addition, two SNPs within the promoter, two SNPs in the 5'-untranslated region (UTR), one SNP and one single nucleotide deletion in the 3'UTR and four rare variations were detected. From the combination of the polymorphisms, it was elucidated that four major haplotypes account for most of the genotypes in the Japanese population. Association with SLE and RA was not detected, although a slight tendency for the increase of BCMA.03 in SLE was observed (P = 0.089). These results indicated that human BCMA is conserved with respect to the amino acid sequence, and evidence for association with SLE and RA was not observed.
10963910 Understanding the adoption of arthritis self-management: stages of change profiles among a 2000 Sep Clinical observations and recent studies suggest that arthritis patients vary considerably in their involvement in self-management efforts. In the literature on health promotion, there is growing recognition that patients may be at different stages of change with respect to the adoption of self-management strategies. The major goal of the present study was to examine whether cluster analysis could be used to identify homogeneous subgroups of patients having persistent arthritis pain based on their responses to a stages of change questionnaire. Participants in this study (103 patients having rheumatoid arthritis and 74 patients having osteoarthritis) completed a stages-of-change measure specific to adoption of a self-management approach to their arthritis. A cluster analysis identified five distinct subgroups of arthritis patients: (1) precontemplation - 44% of the sample; (2) contemplation - 11% of the sample; (3) preparation - 22% of the sample; (4) unprepared action - 6% of the sample; and (5) prepared maintenance - 17% of the sample. These subgroups are generally consistent with what might be expected based on the transtheoretical model of stages of change by Prochaska and DiClemente (Prochaska JO, DiClemente CC. Towards a comprehensive, transtheoretical model of change: states of change and addictive behaviors. In: Miller WR, Heather N, editors. Applied clinical psychology, 2nd ed. Treating addictive behaviors, New York: Plenum Press, 1998. pp. 3-24.), and may have important clinical implications. For example, it is possible that the arthritis subgroups identified may predict arthritis patients' participation in and responsiveness to pain-coping skills training, exercise interventions, or other formal self-management training programs. Also, one may be able enhance the outcomes of self-management interventions for arthritis by tailoring treatment to the patient's particular stage.
10796420 Moderate-term, low-dose corticosteroids for rheumatoid arthritis. 2000 OBJECTIVES: To perform a systematic review of low-dose corticosteroid efficacy in the moderate term for the treatment of rheumatoid arthritis (RA). SEARCH STRATEGY: We conducted a search in MEDLINE from 1966 to 1998, using the keywords "corticosteroids" and "rheumatoid arthritis". We also handsearched all issues of Arthritis and Rheumatism and the Scandinavian Journal of Rheumatology from their dates of first publication to 1994. Furthermore, we examined all Arthritis and Rheumatism abstracts over the 15 year period preceding 1994. References of all identified studies were searched for relevant trials. Authors of unpublished manuscripts were contacted. SELECTION CRITERIA: Studies were selected by two independent reviewers (LC, KS) using a set of predetermined criteria. Specifically, we required that trials be randomized or cross-over and report at least one of the following outcome measures in a quantitative manner: joint tenderness, joint swelling, grip strength, or erythrocyte sedimentation rate (ESR). We also required that trials be of at least three months duration and use prednisone (or a comparable corticosteroid preparation) at a mean dosage of less than or equal to 15 mg/day. We included studies that used either placebo or active drug controls (i.e., comparative studies). DATA COLLECTION AND ANALYSIS: We compared the effectiveness of prednisone to placebo and/or active controls using a fixed effects model for continuous data. A chi square test for homogeneity was performed, and where heterogeneity existed a random effects model was used. We reported results for all available outcomes recommended by the Outcome Measures for Rheumatology Trials (OMERACT) group. These included the number of tender and swollen joints, pain, functional status and ESR. Grip strength was also evaluated. Standardized mean differences (SMD) were used for outcomes assessing the same concept with different scales (eg. swollen joint counts). MAIN RESULTS: Very few studies directly assessed the effectiveness of corticosteroids for RA treatment and many were of poor methodologic quality. Only seven of 34 studies identified by our search met criteria for inclusion. Our results indicated that corticosteroids were significantly more effective than placebo controls for four of six outcomes assessed [standardized mean difference for tender joints = -0.37 (95%CI: -0. 59, -0.14), swollen joints = -0.41 (-0.67, -0.16), pain = -0.43 (-0. 74, -0.12), and functional status = -0.57 (-0.92, -0.22)]. The results for grip strength and ESR were not significant [GS = +0.30 (-0.19, +0.80), weighted mean difference (WMD) for ESR = -7.03 (-18. 06, +4.01)]. The single trial that compared prednisone to aspirin indicated no statistically significant difference between these groups for joint tenderness (0.10 (-0.35, +0.55) and for ESR [0.00 (-11.09, +11.09]. Overall, the four outcomes assessed in the single trial that compared prednisone to chloroquine suggested that the effectiveness of these two agents is similar [SMD for joint tenderness = +0.23 (-0.30, +0.75), swollen joints = +0.43 (-0.11, +0. 96), functional status = -0.27 (-0.80, +0.26), and WMD for ESR = -16. 00 (-30.58, -1.42)]. REVIEWER'S CONCLUSIONS: Based on the limited data available, moderate-term prednisone treatment of RA appears to be superior to placebo and comparable to treatment with aspirin or chloroquine in improving several common rheumatoid arthritis disease activity measures.
11143910 Upper cervical spine surgery in rheumatoid arthritis: retrospective study of 30 patients f 2000 PURPOSE: To evaluate the efficacy of upper cervical spine surgery in symptomatic atlantoaxial instability due to rheumatoid arthritis (RA). MATERIAL AND METHODS: Thirty RA patients (29 women and one man) with a mean age of 56 years were studied retrospectively. Symptomatic forward slippage of the atlas on the axis with a synovial pannus surrounding the odontoid and magnetic resonance imaging evidence of spinal cord compression was present in all 30 patients; 18 patients had vertical translocation of the odontoid and 14 had basilar invagination. Surgery, performed between 1991 and 1997, consisted of occipitocervical fusion in 18 patients and atlantoaxial fusion in 12. Cotrel-Dubousset instrumentation was performed in all 30 patients. RESULTS: Mean follow-up was four and a half years. All patients were satisfied with the procedure and exhibited marked functional gains and objective neurological improvement (by one class in the Ranawat scheme). Stable fusion was documented in all 30 patients. CONCLUSION: Cervical instrumentation and bone grafting seems to provide functional and neurological gains in carefully selected RA patients with atlantoaxial instability and spinal cord compression. Long term follow-up suggests that the benefits are sustained and that morbidity is low.
10507305 Canine rheumatoid arthritis and inflammatory cytokines. 1999 Aug 2 Bioassays were developed to detect canine pro-inflammatory cytokines. These enabled characterisation of these cytokines and their isoforms and provided means for their assay in the joints of dogs with different naturally occurring arthropathies. Canine IL-1 was detected by its induction of proliferation of D10(N4)M cell line, whilst IL-6 had a proliferative effect on B9 cell line. TNFalpha had a cytotoxic effect on WEHI 164 (13) cells. Partial purification of the cytokines was achieved by FPLC ion-exchange chromatography and two isoforms of IL-1 were shown, possibly corresponding to IL-1alpha and IL-1beta. TNFalpha only appeared as one isoform whereas IL-6 showed at least five isoforms, possibly corresponding to the other molecules in the IL-6 family, such as IL-11 and oncostatin M. Analysis of synovial fluids from dogs with osteoarthritis (OA) and rheumatoid arthritis (RA) showed that IL-1 and TNFalpha bioactivity was not readily detectable at increased levels in diseased joints but that IL-6 was significantly increased in both diseases. It is now important to determine the role of IL-6 in OA and RA in the dog, particularly in the induction of proteolytic enzymes which lead to cartilage loss.
9195507 Evidence for reduced Th1 function in normal pregnancy: a hypothesis for the remission of r 1997 Jun OBJECTIVE: The mechanisms underlying the pregnancy induced remission of rheumatoid arthritis (RA) remain unclear. We assessed the hypothesis that it reflects systemic physiologic changes in immune response during gestation. METHODS: We used in vitro whole blood culture systems stimulated with either lipopolysaccharide or phytohemagglutinin to assess cytokine secretion of cells from healthy pregnant and control donors. RESULTS: Interleukin 2 (IL-2) production was decreased during pregnancy, more so in the 3rd trimester, and soluble tumor necrosis factor (TNF) receptor p55 and p75 was increased, again most significantly in the 3rd trimester. TNF-alpha and IL-1 beta were unchanged. CONCLUSION: These findings are consistent with the hypothesized downregulation of Th1 responses during pregnancy. Further studies to assess the relationship with fetal/maternal HLA class II disparity, and eventually the presence or absence of remission in actual patients with RA, are required.
11318600 Mutational analysis of immunoglobulin germline derived Vlambda4B light chains in rheumatoi 2001 May OBJECTIVE: We investigated the somatic mutational pattern of a specific Vlambda light chain variable region (V) gene in rheumatoid arthritis (RA) patients. The Vlambda4B light chain was chosen because of its location on the lambda locus and because of its previously observed use in IgM rheumatoid factors. METHODS: We sequenced 13 different mRNA transcripts of Vlambda4B from the synovium of three different RA patients. These were compared to 31 identifiable Vlambda4B sequences from GenBank, which were obtained from the PBL of patients without RA. RESULTS: A subset of Vlambda4B had a high rate of mutation, especially in the framework regions within the RA synovium. Furthermore, a set of codons within the first complementary determining region of Vlambda4B displayed frequent replacement mutations but did not possess any silent mutations. CONCLUSION: The hypermutation of RA synovial-derived Vlambda4B sequences, especially in the framework areas, may contribute to or may be the result of altered mutational mechanisms and/or prolonged B cell life.
11771022 Hearing loss in rheumatoid arthritis. 2001 Oct OBJECTIVE: Hearing loss, both sensorineural and conductive, has been reported in patients with rheumatoid arthritis (RA). The aim of this study was to try and ascertain the type of hearing loss and to determine the cause for any conductive element noted in these cases. DESIGN AND SETTING: A prospective case-control study in the otolaryngology department of a university teaching hospital in the United Kingdom. METHODS AND OUTCOME MEASURES: This study compared 35 patients with RA with 35 age- and sex-matched controls. All patients had pure-tone audiometry, speech discrimination, tympanometry, acoustic reflex, and acoustic reflex decay carried out. Statistical analysis of the two groups was carried out using the F test for differences in variation and the t-test for independent samples. RESULTS: Sensorineural hearing loss that was statistically significant (p < .05) at 500 Hz, 1 kHz, and 2 kHz in both ears was found in 60% of the RA group and in 34.29% of the control group. A conductive hearing loss that was statistically significant (p < .05) at 250 Hz, 500 Hz, 1 kHz, and 2 kHz in the right and left ears was found in 17.14% of the RA patients and in 5.71% of the control group. Speech discrimination did not show a statistically significant difference between the two groups. Tympanometry showed that the conductive element was probably owing to laxity of the middle ear transducer mechanism. Acoustic reflex and reflex decay did not show statistically significant differences between the two groups. CONCLUSION: Sensorineural hearing loss of the cochlear variety is a common finding in patients with RA, whereas conductive loss, although seen, is much less common. Increased laxity of the middle ear transducer mechanism is the likely cause of the conductive element.
10918218 Expression of vascular endothelial growth factor isoforms and their receptors Flt-1, KDR, 2000 Aug Angiogenesis is an indispensable process in the chronic proliferative synovitis and pannus formation of rheumatoid arthritis (RA). This study examined the expression of vascular endothelial growth factor (VEGF) isoforms and VEGF receptors, Flt-1, KDR and neuropilin-1, in RA and osteoarthritis (OA) synovia, and studied the relationship between their expression and the synovial angiogenesis. By RT-PCR analysis, the isoform VEGF(121) was constitutively expressed in all the RA (17/17 patients) and OA (8/8 patients) synovia. In contrast, the expression of the isoform VEGF(165) was observed in 41% of the RA synovia (7/17 patients), but was undetectable in the OA samples (0/8 patients). The receptor Flt-1 was almost constitutively expressed in RA (15/17 patients) and OA (8/8 patients) synovia, while the expression of KDR was detected in the synovia of six RA patients (6/17 patients; 35%) but none of the OA patients (0/8 patients). The expression of neuropilin-1, an isoform-specific receptor for VEGF(165) which enhances the binding of VEGF(165) to KDR, was also up-regulated in the same RA synovia that expressed KDR. Furthermore, there was a close correlation between the expression of isoform VEGF(165) and that of its receptors KDR and neuropilin-1. Morphometric analysis demonstrated that the vascular density is significantly higher in the RA synovial tissues with expression of VEGF(165), KDR, and neuropilin-1 than in those without their expression (p<0.01). In situ hybridization and immunohistochemical studies indicated that the cells expressing VEGF are macrophage-like synovial lining cells and spindle-shaped cells in the sublining cell layer. These results suggest that the selective up-regulation of the isoform VEGF(165) and its signalling via KDR and neuropilin-1 play an important role in the synovial angiogenesis which occurs in RA.
9486402 Increase of CD57+ T cells in knee joints and adjacent bone marrow of rheumatoid arthritis 1998 Feb The distribution of CD57+ T and CD56+ T cells in patients with RA was examined. In control osteoarthritis patients, these cells exist as a minor population in the peripheral blood. Our data show that in patients with RA, CD57+ T cell levels are elevated in peripheral blood, knee joint fluid, knee synovial membrane and bone marrow (BM), compared with peripheral blood of controls. CD57+ T cells are especially high in knee joint fluid and joint-adjacent BM, while CD56+ T cells show no such increase. CD57+ T cells contain a major population of CD8+ cells and higher proportions of CD4-8- cells and gammadelta T cells than do CD57- T cells. CD57+ T cells in peripheral blood and joint fluid increase with the duration of disease. Erythrocyte sedimentation rate (ESR) is inversely correlated with the proportion of CD57+ T cells in the joint fluid. Although RA frequently occurs in patients with CD3+57+ cell leukaemia, and some CD57+ T cells are likely to be involved in the onset of RA, we suggest that CD57+ T cells may rather suppress inflammation of RA, and other cellular components (e.g. granulocytes) may govern the severity of the inflammation of RA. These CD57+ T cells are probably generated extrathymically in the adjacent BM or joint space.
10807502 A major metabolite of aceclofenac, 4'-hydroxy aceclofenac, suppresses the production of in 2000 Mar OBJECTIVE AND DESIGN: We examined the effects of aceclofenac and its metabolites on the production of pro-collagenase-1/pro-matrix metalloproteinase-1 (proMMP-1), pro-gelatinase A/proMMP-2, pro-stromelysin-1/proMMP-3 and tissue inhibitor of metalloproteinases-1 (TIMP-1) by rheumatoid synovial cells. MATERIALS: Synovial cells were obtained from patients with rheumatoid arthritis. TREATMENT: Cultures of confluent cells were treated with interleukin-1beta (IL-1beta)(1 ng/ml) and/or test drugs (0.3-30 microM) for 48 h. METHODS: Production of proMMPs and TIMP-1 was monitored by Western blotting or gelatin zymography. Prostaglandin E2 (PGE2) was measured by an enzyme immunoassay. RESULTS: 4'-Hydroxy aceclofenac, a major metabolite of aceclofenac, down-regulated both basal and IL-1beta-induced production of proMMP-1 and proMMP-3 at a concentration sufficient to suppress PGE2 production without modulating proMMP-2 or TIMP-1, whereas aceclofenac itself had no marked effect on the production of proMMPs. CONCLUSIONS: Down-regulation of proMMP-1 and proMMP-3 production by 4'-hydroxy aceclofenac may contribute to the therapeutic effect of aceclofenac on rheumatoid arthritis and osteoarthritis.
9627949 Treatment of refractory rheumatoid arthritis with low-dose cyclophosphamide. Long-term fol 1998 Apr Although cyclophosphamide (CYC) is an effective drug in the treatment of refractory rheumatoid arthritis (RA), the application of this drug in RA has largely been abandoned, due to potentially life-threatening adverse events such as myelosuppression and cancer development. However, the question remains open, whether it is possible to balance the toxicity and the efficacy of CYC with low-dose therapy. 108 patients with refractory RA or with vasculitic organ involvement were treated with 50 mg CYC per day. Joint indices and laboratory parameters were gathered prospectively and the occurrence of serious side effects was monitored over a median of 10 years. The efficacy was surveyed in six months intervals. A 50% improvement of the swollen joint count was required to continue therapy. A long-term follow-up was performed to survey the incidence of malignancies. 85 patients dropped out within the first year. Only four patients were treated for longer than 4 years. In the total cohort, 50 patients were withdrawn due to the lack of efficacy, 34 patients had to discontinue because of adverse events, and 9 patients dropped out for both reasons. Gastrointestinal intolerance was the most frequent adverse event that led to the discontinuation of the drug, followed by myelosuppression. Five patients suffered from 6 malignancies occurring after a median of 4.5 years after cessation of treatment. Treatment of RA patients with 50 mg CYC per day resulted in a more favorable rate of serious adverse events and a markedly lower incidence of tumors compared to the treatment with 75 to 150 mg per day described in the literature. However, the long-term efficacy of this regimen was poor in our cohort.
11564377 Rheumatic fever. 2001 Oct Rheumatic fever is a multisystem inflammatory disease that occurs as a delayed sequel to group A streptococcal pharyngitis. It is less common than it was 50 years ago but is still a major cause of heart disease in developing areas of the world. The relationship between the site of infection, the type of causative organism, and susceptibility of the host is essential in the development of the disease. Its major clinical manifestations include carditis, migratory polyarthritis, chorea, erythema marginatum, and subcutaneous nodules. It can manifest as an acute febrile illness consisting of migratory polyarthritis involving the large joints, as carditis and valvulitis, or as Sydenham's chorea with involvement of the central nervous system. The disorder in its milder form resolves itself without sequelae. Carditis is the condition most associated with increased mortality and morbidity and may be fatal in its severe forms. Penicillin is the most appropriate primary and secondary prophylaxis. Anti- inflammatory agents provide symptomatic relief but do not prevent rheumatic heart disease.
9710235 Epitope glycosylation plays a critical role for T cell recognition of type II collagen in 1998 Aug Immunization of mice with type II collagen (CII) leads to collagen-induced arthritis (CIA), a model for rheumatoid arthritis. T cell recognition of CII is believed to be a critical step in CIA development. We have analyzed the T cell determinants on CII and the TCR used for their recognition, using twenty-nine T cell hybridomas derived from C3H.Q and DBA/1 mice immunized with rat CII. All hybridomas were specific for the CII(256-270) segment. However, posttranslational modifications (hydroxylation and variable O-linked glycosylation) of the lysine at position 264 generated five T cell determinants that were specifically recognized by different T cell hybridoma subsets. TCR sequencing indicated that each of the five T cell epitopes selected its own TCR repertoire. The physiological relevance of this observation was shown by in vivo antibody-driven depletion of TCR Valpha2-positive T cells, which resulted in an inhibition of the T cell proliferative response in vitro towards the non-modified CII(256-270), but not towards the glycosylated epitope. Most hybridomas (20/29) specifically recognized CII(256-270) glycosylated with a monosaccharide (beta-D-galactopyranose). We conclude that this glycopeptide is immunodominant in CIA and that posttranslational modifications of CII create new T cell determinants that generate a diverse TCR repertoire.
10209065 Binding of nuclear proteins to the negative regulatory element of the IL-2 gene in lymphoc 1999 Mar T lymphocytes from several autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) exhibit deficient mitogenic response in terms of proliferation and IL-2 production. The expression of the IL-2 gene is regulated by various transcription factors. One of these factors suppresses IL-2 expression and binds to the negative responsive element in the IL-2 gene 5' flanking region (NRE-A). The authors hypothesized that the decreased production of IL-2 by T cells from RA and SLE patients is at least partially caused by high expression of the NRE-A binding protein. To test this hypothesis T cells from healthy donors and patients with RA and SLE were stimulated. Using the electrophoretic mobility shift assay we detected NRE-A DNA-binding proteins in the nuclei of the stimulated cells. No difference was found between NRE-A DNA binding in nuclear extracts of T cells taken from healthy donors and those taken from patients. The specificity of the DNA-protein interactions was ascertained through the use of unlabeled DNA competitors. No correlation was found between DNA-binding and the patients' disease duration or medication. In conclusion, decreased IL-2 biosynthesis by T lymphocytes from RA and SLE patients can not be explained by abnormal expression of the NRE-A DNA-binding protein.
9868328 [Hypercoagulability status previous to total hip and knee arthroplasty: the contribution o 1998 Oct PURPOSE: Starting from a status hypercoagulability previous to substitutive hip and knee surgery, the aim of this work was to investigate the influence of different osteoarthropatic pictures for which arthroplasty is indicated in the activation of the clotting cascade, rheumatoid arthritis (RA) being one of such pictures. PATIENTS AND METHODS: Of 79 patients suitable for prosthetic surgery of hip (53) and knee (26), the preoperative values of several markers, namely, D dimers (D-D), thrombin-antithrombin (TAT) complex, and F1 + 2 prothrombin fragment (F1 + F2) were assessed by enzymoimmunoasay. The mean age of the patients was 65.5 years, and their sex distribution was 50 women and 29 men. The indications for arthroplasty were as follows: osteoarthrosis (62), aseptic necrosis (11), RA (9), articular gout (2), previous fracture (2), more than one diagnosis overlapped in some cases. The results attained were compared with a control group comprised of 33 subjects (16 women and 17 men) with mean age similar to the patient's group (68.06 years). RESULTS: The D-D values in the patients suitable for hip arthroplasty and the TAT values in patients suitable for both types of surgery were significantly higher than those found in the control group (p = 0.012 and 0.01, respectively). The preoperative TAT levels of the RA patients were significantly higher (p = 0.025) than those found in the patients with the other surgical indications. CONCLUSIONS: Previously to the performance of arthroplasty, the patients show hypercoagulative marker values higher than those of age-matched controls. The significant rising of TAT found in RA patients is concordant with the literature, and this fact makes it advisable to include RA among the pathologic situations associated with hypercoagulability, as this is a common indication for substitutive hip and knee surgery with high risk of venous thromboembolic disease.
9263138 Comparative usefulness of C-reactive protein and erythrocyte sedimentation rate in patient 1997 Aug OBJECTIVE: To determine the comparative usefulness of the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the assessment of rheumatoid arthritis (RA) activity and to provide tables and nomograms of normative data in RA allowing the linking and interchange of test values. METHODS: We studied 774 patients with RA seen in the clinic by obtaining complete rheumatologic examinations and laboratory studies. Clinical variables included visual analog scale pain and global severity, joint count, functional disability, depression, and a composite measure of disease activity. In addition, we measured ESR and hemoglobin, and rheumatoid factor (RF), CRP, IgG, IgA, IgM, haptoglobin, alpha 1-antitrypsin, albumin, pre-albumin, and C4 by nephelometry. RESULTS: Median values for CRP were 0.82 mg/dl and ESR 26 mm/h. The average correlation with 7 clinical variables was 0.248 for ESR compared to 0.259 for CRP. But partial correlation analysis showed that a substantial portion of the correlation with ESR is explained by the effect of immunoglobulins, RF, and hemoglobin rather than the acute phase response. Twenty-eight percent of results were discordant between ESR and CRP, and this discordance was explained by the above factors. When discordance occurred, CRP was a better measure of disease activity than ESR. CONCLUSION: Simple comparisons between ESR and CRP suggest that both tests are similar, but partial correlation analysis indicates that part of the correlation between ESR and clinical variables comes from non-acute phase factors. These factors, in turn, are responsible for most of the discordance between ESR and CRP results. Thus, CRP appears to be the better test regarding measurement of the acute phase. Because ESR is sensitive to immunoglobulins and RF, it may measure general severity better than CRP, even though it is a poorer measure of inflammation. This perhaps accounts for the relative equivalence of the tests. The combination of ESR and CRP yields useful information that is often not apparent when only a single test is used.
11550960 Interleukin 10 (IL-10), not IL-4 or interferon-gamma production, correlates with progressi 2001 Sep OBJECTIVE: Both interleukin 4 (IL-4) and IL-10, separately and in combination, and under in vitro and in vivo conditions in animals, have been reported to inhibit characteristics of rheumatoid arthritis (RA) and experimentally induced arthritis. We investigated if IL-10 and IL-4 production, as well as interferon-gamma (IFN-gamma) production, opposing IL-4, were related to RA disease variables. A method was chosen to exclude the influence of age and disease duration. METHODS: We selected RA patients with mild and severe disease. Inclusion criteria were erythrocyte sedimentation rate (ESR) < or = 28 mm/h and > or = 50, C-reactive protein (CRP) < or = 20 and > or = 30, Thompson joint score < or = 60 and > or = 100 and radiographic joint damage score, Sharp score < or = 30 and > or = 40. Age and disease duration were restricted: 30 to 70 years and 5 to 15 years, respectively. Peripheral blood mononuclear cells were isolated and the ex vivo 48 h production of T cell IL-10, IL-4, and IFN-gamma (after CD3-CD28 stimulation) was assessed and was correlated to clinical variables. RESULTS: Only IL-10 production differed significantly between the 2 groups of RA patients, being highest in the "mild" group. Taking all patients together, a strong negative correlation was found between IL-10 production and radiographic joint damage (r = -0.53, p < 0.001) as well as progression of joint damage (r = -0.56, p < 0.0001). Similar negative correlations, although less powerful, were found between IL-10 production and ESR, CRP, and Thompson joint score. No correlation was found for IFN-gamma, IL-4, or the ratio of the 2 with disease activity variables or joint damage. CONCLUSION: The findings suggest that the high IL-10 production found in patients with RA may be protective, especially against progression of joint destruction in RA.
9184845 Immunocytochemical identification of metallothionein-positive cells in rheumatoid synovium 1997 Apr Metallothionein is a ubiquitous low molecular weight metalloprotein with powerful protective properties against oxygen radical-mediated cytotoxicity associated with inflammatory processes. In rheumatoid arthritis, the inflammatory damage to the synovium appears to be mediated by free radicals released by the high concentration of neutrophils found in the synovial fluid of the inflamed joint. Synovial tissue obtained during routine surgery on rheumatoid and non-rheumatoid joints was subjected to an indirect immunoperoxidase protocol for the immunolocalization of metallothionein using mouse monoclonal anti-metallothionein antibody E9, reactive against the two major isoforms of mammalian metallothionein. A layer of large dendritic-like cells situated subsynovially in the rheumatoid synovium stained very positively for the metalloprotein, both cytoplasmically and in their nuclei. These cells were not found in non-rheumatoid osteoarthritic or in undamaged synovial tissue associated with traumatic joint injury. An attempt was made to investigate their lineage using a series of antibody markers against epithelial cells, endothelial cells, smooth muscle, mesothelial cells, fibroblasts, neutrophils, dermal dendrocytes, macrophages, low and high molecular weight cytokeratin as well as a cell proliferation marker. From our results, it is suggested that these metallothionein-positive cells are probably myofibroblasts similar to the highly motile cells present in granulation tissue. They may originate from perivascular areas of synovium and their movement into the inflamed synovium may reflect the cytoprotective role of metallothionein acting as a free radical scavenger against oxidative damage.