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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
9330932 Bone scintigraphy of the hands in early stage lupus erythematosus and rheumatoid arthritis 1997 Oct OBJECTIVE: To evaluate retrospectively the discriminatory value of bone scintigraphy, especially spot images of the hands, in differentiating early stage systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: Data from 19 patients with SLE (3 men, 16 women) and 20 patients with RA (6 men, 14 women), presenting with early stage articular disease (arbitrarily defined as articular complaints for no longer than 3 mo), were reviewed. At this stage, radiographs were normal in all patients. In all 39 patients, total body bone scintigraphy with spot images of the hands was performed as part of a complete diagnostic investigation. For differentiation between SLE and RA in early disease stage, less extensive semiquantitative description in 3 categories (normal, diffuse mildly increased, and (multi)focal moderately to markedly increased tracer accumulation) proved to be sufficient. Locations of bone scintigraphic findings were correlated to clinical findings. RESULTS: In RA, bone scintigraphy revealed foci of moderate to markedly increased tracer accumulation, corresponding to the sites of clinical synovitis in all patients. In 10 patients with SLE, bone scintigraphy images of the hands were normal, and in 9 patients diffuse mildly increased tracer accumulation was observed. CONCLUSION: The data suggest bone scintigraphy may be useful to differentiate SLE from RA in early stage disease.
9213790 [Favorable results of early 2nd-stage medication in rheumatoid arthritis]. 1997 Apr 12 OBJECTIVE: To compare the effects of treatment with and without 'slow-acting antirheumatic drugs' (SAARDs) for patients with recent-onset rheumatoid arthritis (RA). DESIGN: Open randomized clinical trial. SETTING: Outpatient clinics of six medical centers, the Netherlands. METHOD: The study population consisted of 304 consecutive patients with recently diagnosed RA. A therapeutic strategy with delayed introduction of a SAARD was compared with a strategy comprising early start of SAARD treatment. Primary endpoints were functional disability, pain, joint score, erythrocyte sedimentation rate and progression of radiological abnormalities at 12 months. RESULTS: Four of the five endpoints improved statistically significantly more in the early-SAARD group than in the non-SAARD group; radiological abnormalities progressed at an equal rate in the two groups. Adverse reactions remained at an acceptable level and were the same in the two groups. CONCLUSION: Early introduction of a SAARD was more beneficial than a therapeutic strategy with delayed introduction of a SAARD for patients with recently diagnosed RA.
9762375 Minocycline-associated tooth staining. 1998 Sep OBJECTIVE: To describe a case of tooth discoloration in an adult after minocycline treatment for arthritis. CASE SUMMARY: A 68-year-old white women presented with blue-black staining of her lower anterior teeth after 4 months of minocycline therapy for arthritis. Her other medications are not known to cause discoloration of teeth. While the patient continued taking minocycline, her dentist was not able to remove the discoloration. Within 1 month after discontinuation of the minocycline, the dentist was able to remove the discoloration entirely. DISCUSSION: Minocycline, a synthetic derivative of tetracycline, has been shown to cause abnormal pigmentation of the skin, thyroid gland, nails, bone, sclera, and conjunctiva in adults. It also has been shown to cause tooth discoloration in a few patients. This case is unusual in that the tooth discoloration disappeared after discontinuing minocycline therapy. CONCLUSIONS: This complication of minocycline is more commonly thought of in the pediatric population. However, clinicians need to be aware of this adverse drug reaction, as this agent may be used increasingly in the treatment of adults with arthritis.
11386807 Patients with rheumatoid arthritis adapt differently to repetitive painful stimuli compare 2001 May The aim of the study was to investigate whether there are changes of the nociceptive system in patients with chronic inflammatory joint pain. A pain model was used which is based on the recording of cortical chemo-somatosensory event-related potentials (CSSERP) after nociceptive stimulation of the nasal mucosa with gaseous carbon dioxide (CO(2)). Twenty-five patients with rheumatoid arthritis (RA) were compared to healthy controls matched for age and gender. Responses to both different intensities of painful stimuli and constant intensities of series of 4 stimuli were analysed. When testing increasing CO(2) concentrations ratings and CSSERP amplitudes increased for both patients and controls. However, when repetitive stimulation was performed with an interval of 2s CSSERP amplitudes N1 were significantly greater in RA patients. It is hypothesized that chronic inflammatory joint pain changes nociceptive processing in terms of generalized changes of the nociceptive system which may amplify chronic pain.
10986305 Radiographic damage of large joints in long-term rheumatoid arthritis and its relation to 2000 Sep OBJECTIVE: To describe the extent of radiographic damage of large joints in long-term rheumatoid arthritis (RA) and its relationship to small joint involvement and physical function. METHODS: After 12 yr of follow-up, radiographs of all large joints (Larsen large joint score 0-60) of 105 recent RA patients were assessed. Correlations were evaluated between the Larsen large joint score and radiographic damage of the hands and feet as measured by the van der Heijde modification of the Sharp score (SHS) and the health assessment questionnaire (HAQ). We determined the relative contributions of radiographic damage of small and large joints, disease activity and psychological function to the HAQ. RESULTS: The median Larsen large joint score was 3. In 54% of the patients at least one large joint was erosive. The correlation of the Larsen score with the SHS and HAQ scores was 0.76 and 0.60, respectively. Disease activity and radiographic damage of the large joints were the major determinants of the HAQ score. CONCLUSION: Large joint involvement after 12 yr of follow-up is extensive and is associated with functional disability. Large joint involvement is closely associated with small joint involvement.
10943872 Modulation of inflammation and metalloproteinase expression in synovial tissue by leflunom 2000 Aug OBJECTIVE: Leflunomide and methotrexate have proven to be efficacious in reducing joint inflammation and slowing destruction in clinical trials of patients with rheumatoid arthritis (RA). This study was conducted to provide more insight into the mechanism of action of these agents in synovial tissue. METHODS: In a 2-center, prospective, randomized, double-blind clinical trial, we compared leflunomide (20 mg/day, after a 3-day 100 mg/day loading dose) and methotrexate (increased stepwise to 15 mg/week) treatment in patients with active RA. Paired synovial tissue biopsy samples were obtained by knee arthroscopy at baseline and after 4 months of treatment. Frozen synovial tissue sections were stained for macrophages (CD68), T cells (CD3), adhesion molecules (intercellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule 1 [VCAM-1]), cytokines (tumor necrosis factor alpha, interleukin-1beta [IL-1beta]), matrix metalloproteinase 1 (MMP-1), and tissue inhibitor of metalloproteinases 1 (TIMP-1). RESULTS: Paired synovial tissue sections were available in 35 patients (16 taking leflunomide, 19 taking methotrexate). Both drugs displayed equal clinical efficacy, with 8 leflunomide-treated patients (50%) and 10 methotrexate-treated patients (53%) fulfilling the American College of Rheumatology 20% response criteria. Both compounds showed similar effects on synovial tissue: reduced numbers of macrophages and reduced ICAM-1 and VCAM-1 expression were noted after 4 months of treatment. Both leflunomide- and methotrexate-treated patients exhibited a decreased MMP-1:TIMP-1 ratio in the synovial tissue. In the subset of patients fulfilling the 20% response criteria of the American College of Rheumatology, a more pronounced reduction in the expression of ICAM-1, VCAM-1, IL-1beta, and MMP-1 was found compared with the nonresponders. CONCLUSION: Leflunomide and methotrexate are clinically efficacious drugs that interfere with mechanisms involved in joint inflammation and destruction of joint integrity.
10693889 Rheumatoid arthritis exacerbation caused by exogenous interleukin-12. 2000 Feb Interleukin-12 (IL-12) is a pleiotropic cytokine with proinflammatory, immunoregulatory, antitumor, and antimetastatic properties. It plays a crucial role in the development of the Th1 response and subsequent interferon-gamma production and enhancement of cell-mediated cytotoxicity. Recently, IL-12 has been used as an experimental therapy for cancer. Given the multiple immunomodulatory properties of IL-12, there are potential concerns associated with its clinical use. Of special interest are the possible side effects of IL-12 therapy in patients with autoimmune diseases, especially those that are T cell mediated, such as rheumatoid arthritis (RA). We present a case of severe RA exacerbation caused by treatment with IL-12 for metastatic cervical cancer. This is the first reported case of RA flare caused by exogenous IL-12.
10370372 C/EBP beta in rheumatoid arthritis: correlation with inflammation, not disease specificity 1999 Jun Rheumatoid arthritis synovial tissue was examined and compared with osteoarthritis tissue for the presence of the nuclear transcription factor C/EBP beta (NF-IL-6). The region (lining or sublining), cell type, and subcellular distribution (cytoplasmic or nuclear) of the expression of C/EBP beta was characterized. Rheumatoid arthritis synovial fluid and blood and normal peripheral blood were also examined. C/EBP beta was detected in the synovial lining and in sublining cells of synovial tissue from patients with both rheumatoid and osteoarthritis. A significant (P < 0.001 and < 0.05, respectively) increase in the percentage of cells with nuclear staining was seen in the lining layer, compared to cells in the sublining region, in rheumatoid and osteoarthritis. In both diseases a strong correlation (r = 0.79, P < 0.001) was observed between the percentage of cells in the synovial lining that were positive for nuclear C/EBP beta and lining cell depth. Two-color immunohistochemistry demonstrated that both macrophages and fibroblast-like synoviocytes were positive for nuclear C/EBP beta. The presence of C/EBP beta was confirmed by immunohistochemistry and Western blot analysis with isolated synovial fibroblasts. Nuclear C/EBP beta was also detected in rheumatoid synovial fluid monocytes/macrophages, but not in lymphocytes or neutrophils. Western blot analysis confirmed the presence of C/EBP beta in these cells. The intensity of C/EBP beta staining was greater (P < 0.001) in synovial fluid monocytes than in those from normal or rheumatoid peripheral blood. In conclusion, the enhanced nuclear staining for C/EBP beta in the synovial lining, compared to the sublining, suggesting activation in the lining, and the positive correlation of lining layer depth with the percentage of cells in the lining positive for nuclear C/EBP beta, suggest a potential role for C/EBP beta in chronic inflammation. The regulation of the production or activity of C/EBP beta, to inhibit inflammatory mediator expression by synovial macrophages and fibroblasts, offers a novel approach to therapeutic intervention.
9082940 CR1, CD35 in synovial fluid from patients with inflammatory joint diseases. 1997 Mar OBJECTIVE: To investigate synovial fluid (SF) for the presence of CR1 and to study its relationship to SF leukocytes and to serum levels of soluble CR1 (sCR1) in patients with rheumatic diseases. METHODS: Synovial fluids were collected from 35 patients with rheumatoid arthritis (RA) and 26 patients with other inflammatory joint diseases. Total CR1 in the SF and serum were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) that recognized both soluble and transmembrane forms of CR1. The characteristics of CR1 in SF were analyzed by ultracentrifugation and by a second ELISA specific for transmembrane CR1. RESULTS: CR1 was found in all SF samples tested (range 5-281 ng/ml). SF CR1 was higher in patients with RA (mean +/- SD 81 +/- 66 ng/ml) than in those with other inflammatory joint diseases (31.8 +/- 23.8 ng/ml) (P < 0.001). Serum sCR1 was not significantly increased in the patients compared with the normal subjects. There was no correlation between serum sCR1 and SF CR1. In 44% of the patients, the SF CR1 level was higher than the serum sCR1 level. A fraction (30-80%) of SF CR1 was pelleted by ultracentrifugation and, unlike serum sCR1, it reacted in an ELISA specific for transmembrane CR1. Thus, SF contained 2 forms of CR1: a membrane-associated and a soluble form, which was confirmed by sucrose density-gradient ultracentrifugation. SF CR1 levels correlated directly with the number of SF total leukocytes and polymorphonuclear leukocytes (PMN). These 2 forms of CR1 were also found in the supernatant of in vitro-activated PMN from normal subjects. SF CR1 exhibited the capacity to act as a cofactor for the factor I degradation of C3b. CONCLUSION: CR1 is found in the SF of patients with joint inflammation. The data suggest that SF CR1 originates from the infiltrating leukocytes, which shed both a soluble and a membrane-associated form. Whether SF CR1 participates in the local regulation of complement activation remains to be examined.
10820257 Molecular basis for recognition of an arthritic peptide and a foreign epitope on distinct 2000 Jun 1 KRN TCR transgenic T cells recognize two self-MHC molecules: a foreign peptide, bovine RNase 42-56, on I-Ak and an autoantigen, glucose-6-phosphate isomerase 282-294, on I-Ag7. Because the latter recognition event initiates a disease closely resembling human rheumatoid arthritis, we investigated the structural basis of this pathogenic TCR's dual specificity. While peptide recognition is altered to a minor degree between the MHC molecules, we show that the receptor's cross-reactivity critically depends upon a TCR contact residue completely conserved in the foreign and self peptides. Further, the altered recognition of peptide derives from discrete differences on the MHC recognition surfaces and not the disparate binding grooves. This work provides a detailed structural comparison of an autoreactive TCR's interactions with naturally occurring peptides on distinct MHC molecules. The capacity to interact with multiple self-MHCs in this manner increases the number of potentially pathogenic self-interactions available to a T cell.
11520463 TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impa 2001 Aug BLyS and APRIL have similar but distinct biological roles, mediated through two known TNF receptor family members, TACI and BCMA. We show that mice treated with TACI-Ig and TACI-Ig transgenic mice have fewer transitional T2 and mature B cells and reduced levels of circulating immunoglobulin. TACI-Ig treatment inhibits both the production of collagen-specific Abs and the progression of disease in a mouse model of rheumatoid arthritis. In BLyS-deficient mice, B cell development is blocked at the transitional T1 stage such that virtually no mature B cells are present, while B-1 cell numbers are relatively normal. These findings further elucidate the roles of BLyS and APRIL in modulating B cell development and suggest that BLyS is required for the development of most but not all mature B cell populations found in the periphery.
11108572 Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoa 2000 Jun Concentrations of interleukin (IL)-6 and IL-8 in serum and synovial fluid obtained from patients with osteoarthritis (OA) of the knee were determined by the chemiluminescence-ELISA (CL-ELISA) method, the sensitivity of which is 100-1,000 times greater than that of the conventional ELISA method. The results were compared with those obtained from patients with rheumatoid arthritis (RA) and from healthy subjects. The mean IL-6 and IL-8 levels in synovial fluid indicated higher concentrations in RA than in OA. The IL-6 and IL-8 levels in serum were significantly higher in RA and OA relative to controls. Among OA patients in whom remarkable improvement was noted in hydrarthrosis, the synovial fluid IL-6 and IL-8 levels at the initial examination were relatively higher, and were markedly decreased after treatment with sodium hyaluronate (NaHA). Among those in whom no improvement was noted in hydrarthrosis, the synovial fluid IL-6 and IL-8 levels at the time of initial examination were relatively lower, and hydrarthrosis was not significantly improved even after treatment with NaHA. In addition, there was a tendency for the synovial fluid IL-6 and IL-8 levels to decrease as HA levels increased. Evaluation of X-ray findings revealed that the IL-6 levels in synovial fluid at the initial examination in low-grade cases tended to be significantly higher than in high-grade cases. In low-grade cases, as determined by X-ray findings, there was a significant decrease in IL-6 levels in synovial fluid after treatment with NaHA.
10889331 New gamma-fluoromethotrexates modified in the pteridine ring: synthesis and in vitro immun 2000 May Our continuing program to develop new antifolate drugs useful against rheumatoid arthritis led us to modify the pteridine ring of gamma-fluoromethotrexate. Pyrrolopyrimidine derivatives 1e and 1t were found to exhibit potent suppressive effects on the responses of both T and B cells to mitogens, although tetrahydropyridopyrimidine derivatives 2e and 2t and quinazoline derivatives 3e, 3t and 4e showed very weak suppressive activities. Thus, conversion of the pteridine ring of gamma-fluoromethotrexate to a pyrrolopyrimidine ring led to a new potential antirheumatic compound.
9602769 Cumulative revision rate with the Scan Hip Classic I total hip prosthesis. 1,660 cases fol 1998 Apr We analyzed the cumulative revision rate in 1,474 patients (1,660 hips) operated on with a cemented Scan Hip Classic I prosthesis from November 1983 to January 1994 at Lund University Hospital. The revision rate was analyzed for 3 diagnoses--arthrosis, rheumatoid arthritis and complication after a hip fracture--and for 2 head diameters--22 and 32 mm. Until January 1996, 36 hips were revised: 31 because of aseptic loosening, 3 because of dislocation and 2 because of infection. The overall revision rate was 5.6% after 10 years and was similar in arthrosis, rheumatoid arthritis and fracture cases. Due to revisions because of dislocation in the 22 mm group, the total revision rate was lower in the 32 mm group (p = 0.03).
9572644 Perforation of the sigmoid colon in a rheumatoid arthritis patient treated with methylpred 1998 We describe a 61 year-old caucasian male diagnosed with rheumatoid arthritis. He was started on methylprednisolone pulses because of a severe flare of symmetric polyarthritis while he was on weekly intramuscular methotrexate and low-dose oral prednisone. After the second pulse of methylprednisolone the patient suddenly developed severe abdominal pain with free air under the right hemidiaphragm in the chest roentgenogram. The emergency surgery revealed the perforation of a colonic diverticulum. We suggest that methylprednisolone pulses should be carefully used in those patients over 50 years of age and/or people with demonstrated or suspected diverticular disease.
10074595 Remission of the nephrotic syndrome in a patient with renal amyloidosis due to rheumatoid 1998 Nov A 46-year-old woman developed nephrotic syndrome secondary to rheumatoid arthritis (RA). A renal biopsy showed deposition of amyloid fibrils in the subendothelial space of the glomerular capillary walls. After treatment with prednisolone (PSL, 40 mg/day), the levels of C-reactive protein (CRP) and serum amyloid A decreased to within normal limits for 2 weeks. However, the nephrotic syndrome persisted for 6 months after the therapy. To maintain the suppression of disease activity and to reduce PSL, methotrexate (5 mg/week) was added. The nephrotic syndrome resolved gradually, and the level of serum albumin returned to normal. Although renal prognosis of patients with nephrotic syndrome due to amyloidosis caused by RA has been considered poor, adequate and long-term treatment of RA with antiinflammatory drugs, including PSL and methotrexate, is useful for patients with secondary amyloidosis complicated by RA.
10752585 Rheumatologic serologies in secondary restless legs syndrome. 2000 Mar Diagnostic criteria for restless legs syndrome (RLS) have been established; however, the pathophysiology of this common condition remains elusive. Several secondary forms of RLS potentially include renal failure, iron deficiency, pregnancy, and neuropathy. RLS has also been reported in approximately 25% of patients diagnosed with rheumatoid arthritis and Sjögren's syndrome. We performed clinical and serologic evaluations on 68 patients diagnosed with RLS to determine how many may have concurrent rheumatologic disease that could be causing their RLS symptoms. We compared these with other postulated secondary causes of RLS. No patient had clinical evidence of rheumatologic disease, and only four had any positive serologic evaluations (two positive SSA/SSB and two mildly elevated RF titers). Three of these had a positive family history for RLS. Patients without a family history of RLS did have lower ferritin levels, more cases of neuropathy, and an older age at symptom onset. We do not think rheumatologic disease represents a significant secondary cause of RLS and do not recommend serologic investigation unless there are overt clinical signs. In contrast, our study suggests that neuropathy and serum iron deficiency do represent secondary forms of RLS.
10975477 Immunoadsorption of immunoglobulins alters intracytoplasmic type 1 and type 2 T cell cytok 2000 Aug Intracellular cytokine staining and flow cytometry were used to investigate whether immunoadsorption (IA) of immunoglobulins alters intracytoplasmic cytokine production in CD4+ and CD8+ T cells from the blood of patients with refractory rheumatoid arthritis (n = 7), membrane proliferative glomerulonephritis (n = 1), and Goodpasture's syndrome (n = 1). Four patients (Group 1) showed severely depressed production of TNF-alpha, IL-2, IFN-gamma, and IL-4 by CD4+ and CD8+ T cells and responded to 3 IA sessions with significant increases in CD4+TNF-alpha+, CD4+IL-2+, and CD8+IL-2+ T cells. Also, a tendency toward increased percentage levels of CD4+ T cells producing IFN-gamma or IL-4 and of CD8+ T cells producing either TNF-alpha or IFN-gamma was seen, but due to the small number of patients investigated, these differences did not attain statistic significance. Group 2 (n = 5) showed unimpaired intracellular cytokine levels and responded to IA with a heterogeneous pattern of changes in TNF-alpha, IL-2, IFN-gamma, and IL-4 production, but these alterations were smaller than those in Group 1. The present findings indicate that the extracorporeal removal of immunoglobulins by anti-IgG or protein A adsorber columns has an impact on T cell immunity and suggest that modulating effects on cellular immune system function are involved in the mode of action of IA.
9820607 Description of a new DRB1*11 allele (DRB1*1132). 1998 Oct We describe a new DRB1*11 allele which is similar to DRB1*11011 except at codon 74, where a GCG is changed for a GTG leading to an alanine/valine substitution. This new allele was carried by a Caucasian patient suffering from rheumatoid arthritis and by her healthy daughter. The motif at codon 74 of the new DRB1*11 is not found in any other known DRB alleles, nor among the published DQA1, DQB1, DPA1 or DPB1 alleles, and therefore suggests a mechanism of point mutation.
9214421 Mycoplasma infection and rheumatoid arthritis: analysis of their relationship using immuno 1997 Jul OBJECTIVE: To examine the relationship between infection with Mycoplasma and the development of rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). METHODS: Immunoblotting of patient synovial fluid and sera on detergent-phase membrane protein extracts of various Mycoplasma species was carried out to learn whether patients exhibited serologic evidence of previous exposure to mycoplasmas. Moreover, an ultrasensitive polymerase chain reaction (PCR) method was developed for assessing whether Mycoplasma DNA could be detected in synovial fluid from patients and controls. RESULTS: Immunoblotting provided serologic evidence of previous Mycoplasma exposure in patients and controls. The genus-specific PCR detected known human Mycoplasma species and could reliably detect <5 copies of Mycoplasma hominis, Mycoplasma fermentans, or a molecular mimic control in synovial fluid. Repeat testing revealed no evidence of Mycoplasma DNA in patient synovial samples. CONCLUSION: This study provided serologic evidence suggesting that, while previous exposure to Mycoplasma was common, there was no detectable persistence of Mycoplasma DNA in the synovial fluid or tissue of patients with RA or JRA.