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ID PMID Title PublicationDate abstract
12223108 Cardiovascular risk in rheumatoid arthritis versus osteoarthritis: acute phase response re 2002 Rheumatoid arthritis (RA) patients experience a markedly increased frequency of cardiovascular disease. We evaluated cardiovascular risk profiles in 79 RA patients and in 39 age-matched and sex-matched osteoarthritis (OA) patients. Laboratory tests comprised ultrasensitive C-reactive protein (CRP) and fasting lipids. Insulin sensitivity (IS) was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI) in all OA patients and in 39 of the RA patients. Ten RA patients were on glucocorticoids. RA patients exercised more frequently than OA patients (chi2 = 3.9, P < 0.05). Nine RA patients and one OA patient had diabetes (chi2 = 4.5, P < 0.05). The median CRP, the mean QUICKI and the mean high-density lipoprotein (HDL) cholesterol were 9 mg/l (range, 0.5-395 mg/l), 0.344 (95% confidence interval [CI], 0.332-0.355) and 1.40 mmol/l (95% CI, 1.30-1.49 mmol/l) in RA patients, respectively, as compared with 2.7 mg/l (range, 0.3-15.9 mg/l), 0.369 (95% CI, 0.356-0.383) and 1.68 mmol/l (95% CI, 1.50-1.85 mmol/l) in OA patients. Each of these differences was significant (P < 0.05). After controlling for the CRP, the QUICKI was similar in RA and OA patients (P = 0.07), while the differences in HDL cholesterol were attenuated but still significant (P = 0.03). The CRP correlated with IS, while IS was associated with high HDL cholesterol and low triglycerides in RA patients and not in OA patients. A high CRP (>/= 8 mg/l) was associated with hypertension (chi2 = 7.4, P < 0.05) in RA patients. RA glucocorticoid and nonglucocorticoid users did not differ in IS and lipids (P > 0.05). Excess cardiovascular risk in RA patients as compared with OA patients includes the presence of decreased IS and HDL cholesterol in RA patients. The latter is only partially attributable to the acute phase response. The CRP, IS, HDL cholesterol, triglycerides and hypertension are inter-related in RA patients, whereas none of these relationships were found in OA patients.
12718499 What employees with rheumatoid arthritis, diabetes mellitus and hearing loss need to cope 2003 Apr OBJECTIVES: This study attempted to determine factors that help currently employed people with rheumatoid arthritis, diabetes mellitus or hearing loss to continue working. METHODS: This was a qualitative study that used three concept-mapping sessions. Sixty-nine participants (rheumatoid arthritis 21, diabetes mellitus 23, and hearing loss 25) were recruited from the patient records of the rheumatology, diabetes, and audiology outpatients of the Academic Medical Center (AMC), Amsterdam, and referrals from occupational physicians and patient associations. An arthritis consultant, a diabetes consultant, and an audiologist screened the patients for the used illness inclusion criteria. A researcher screened the patients for the inclusion criteria of age and work. RESULTS: The main factors enabling employees to continue working were ability to cope with the illness, support from management and colleagues, adequate work conditions, support of patient organizations and society, support of medical professionals and facilities, and benefits. The three groups of employees rated the priority of these factors differently. For the employees with rheumatoid arthritis, the support of management was the most important, followed by self-acceptance, self-efficacy, and professional advice on how to cope at work. For those with diabetes mellitus, self-acceptance, self-care, and support from management, colleagues and health professionals were the most important. For employees with hearing loss, being well informed about hearing equipment, reimbursement, and self-acceptance were the most important. A topic list was developed that can be used by health professionals as a guideline for exploring the work-related problems of patients with a chronic disease. CONCLUSION: The results provide an understanding of the needs chronically ill employees have at work and the areas to which health professionals need to pay attention.
12905466 Rheumatoid arthritis is a heterogeneous disease: evidence for differences in the activatio 2003 Aug OBJECTIVE: To generate a molecular description of synovial tissue from rheumatoid arthritis (RA) patients that would allow us to unravel novel aspects of pathogenesis and to identify different forms of disease. METHODS: We applied complementary DNA microarray analysis to profile gene expression, with a focus on immune-related genes, in affected joint tissues from RA patients and in tissues from osteoarthritis (OA) patients as a control. To validate microarray data, real-time polymerase chain reaction was performed on genes of interest. RESULTS: The gene expression signatures of synovial tissues from RA patients showed considerable variability, resulting in the identification of at least two molecularly distinct forms of RA tissues. One class of tissues revealed abundant expression of clusters of genes indicative of an involvement of the adaptive immune response. Detailed analysis of the expression profile provided evidence for a prominent role of an activated signal transducer and activator of transcription 1 pathway in these tissues. The expression profiles of another group of RA tissues revealed an increased tissue remodeling activity and a low inflammatory gene expression signature. The gene expression pattern in the latter tissues was reminiscent of that observed in the majority of OA tissues. CONCLUSION: The differences in the gene expression profiles provide a unique perspective for distinguishing different pathogenetic RA subsets based on molecular criteria. These data reflect important aspects of molecular variation that are relevant for understanding the biologic dysregulation underlying these subsets of RA. This approach may also help to define homogeneous groups for clinical studies and evaluation of targeted therapies.
11934970 Dendritic cells in rheumatoid synovial membrane after total removal of the hyaline articul 2002 Mar OBJECTIVE: To investigate the effect of total removal of the hyaline articular cartilage on dendritic cells in synovial membrane in rheumatoid arthritis (RA) or ankylosing spondylitis (AS). PATIENTS AND METHODS: Immunohistochemical staining for two dendritic cell markers, CD35 and RFD1, was carried out on synovial membrane specimens from arthritis patients undergoing primary (n=10) or revision (n=8) total hip replacement (THR). The results are expressed as the number (mean+/-standard deviation) of positive cells per 1000 total cells. RESULTS: CD35-(112+/-9) and RFD1-(27+/-5) positive cells were found in all primary RA synovial membrane, while only two out of eight synovial membrane samples from revision THR contained CD35-positive follicular dendritic cells (nine and 12 cells), and no revision samples contained any RFD1-positive interdigitating dendritic cells. CONCLUSION: Removal of the hyaline articular cartilage reduces the infiltration and functional differentiation of dendritic cells in synovial membrane. Our findings suggest that the antigen driving chronic arthritis/synovitis is contained in the hyaline articular cartilage.
15012711 Antineutrophil cytoplasmic antibody-negative pauci-immune crescentic glomerulonephritis as 2003 Oct Clinically relevant renal lesions in rheumatoid arthritis (RA) are not common. More often renal involvement is related to complications of therapy than the disease itself. The most common forms of primary renal disease in RA are membranous glomerulonephropathy and a pure mesangial proliferative glomerulonephritis. Some studies have described the association between crescentic glomerulonephritis (crescentic GN) and RA, but they were all found to be perinuclear antineutrophil cytoplasmic antibody (p-ANCA) positive. However, RA associated with ANCA negative pauci-immue crescentic GN has not been reported. This is a case report of a 37-year-old female with RA who initially presented with general oedema and acute deterioration of renal function. The renal biopsy revealed ANCA negative pauci-immune crescentic GN. The patient was treated with steroid pulse and plasmapheresis, but not cyclophosphamide because of severe urosepsis. Despite the use of aggressive therapy, her renal function was not improved and she underwent maintenance haemodialysis thereafter. Because ANCA negative crescentic GN may occur in RA patients without frank systemic vasculitis, but with severe clinical manifestation, a heightened suspicion for a relatively 'silent' crescentic GN would have led to the correct diagnosis and appropriate treatment.
15379178 Reactive arthritis. Immune-mediated synovitis or joint infection. 2004 Jul Reactive arthritis is one form of the seronegative Spondyloarthropathies. Susceptibility to reactive arthritis is closely linked to individuals who have the genetic predisposition to the HLA-B27 allele (gene form). Although there is a reactive-inflammatory joint reaction present, the synovium is not damaged by infectious agents (bacteria, fungi, or virus). This article discusses the pathogenesis of reactive arthritis.
12687538 Risk of malignant lymphomas in patients with rheumatoid arthritis and in their first-degre 2003 Apr OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk for malignant lymphomas. Both conditions display a familial aggregation, and there are reports of RA and malignant lymphomas occurring in the same families. This study was undertaken to determine the risk of malignant lymphomas in first-degree relatives of RA patients, in order to investigate whether the increased risk of malignant lymphomas in RA could be due to genetic or environmental risk factors common to both conditions, rather than being a consequence of the rheumatic disease. METHODS: Using Swedish nationwide and population-based registers, we identified 76,527 patients hospitalized with RA in 1964-1999 and 70,290 first-degree relatives of a subset of these patients. These subjects were followed up for more than 3 decades, and information on cancer occurrence was recorded. RESULTS: Patients with RA had a significantly increased risk of malignant lymphomas (535 cases; standardized incidence ratio [SIR] 2.00, 95% confidence interval [95% CI] 1.83-2.17), which was apparent for up to 2 decades of followup. Among the first-degree relatives without RA, no increased risk of malignant lymphomas was found overall, although modest and nonsignificantly elevated risk estimates were observed in subgroups. With respect to childhood cancer (0-14 years of age), we observed an increased risk of Hodgkin's lymphoma (5 cases; SIR 3.18, 95% CI 1.03-7.42). CONCLUSION: Patients with RA are at a markedly, but possibly time-limited, increased risk for malignant lymphomas. There is little to suggest a prominent role for coinherited or common environmental risk factors in malignant lymphomas arising in the context of RA. Instead, lymphomas complicating RA appear to be a direct consequence of the inflammation or its treatment.
12707581 Apoptosis in rheumatoid arthritis. 2003 May Apoptosis is a key mechanism that regulates tissue composition and homeostasis. Alterations in the apoptosis of synovial cells have been described in residential synoviocytes as well as inflammatory cells and associated with the pathogenesis of rheumatoid arthritis. These changes constitute hallmarks of synovial cell activation and contribute to both chronic inflammation and hyperplasia. Rheumatoid arthritis synovial fibroblasts are affected most prominently, and their resistance to apoptosis has been linked closely to the progressive destruction of articular cartilage. Although a detailed understanding of mechanisms that prevent synovial fibroblasts from programmed cell death is lacking, several antiapoptotic molecules have been identified. Among them, downstream modulators of Fas-signaling, such as sentrin-1/small ubiquitin-like modifier (SUMO)-1 and Fas-associated death domain-like interleukin (IL)-1beta-converting enzyme-inhibitory protein (FLIP), as well as transcriptional regulators such as NFkappaB, Stat3, and p53, have been suggested to regulate apoptosis most prominently. Current efforts are aimed at elucidating the specific role of these molecules in regulating the apoptosis of rheumatoid fibroblasts and at identifying molecular targets to interfere with altered apoptosis.
15175782 An unusual cause of pulmonary haemorrhage in a patient with rheumatoid arthritis. 2004 May INTRODUCTION: Pulmonary haemorrhage is a rare presentation of strongyloides hyperinfection. CLINICAL PICTURE: A 69-year-old female patient with rheumatoid arthritis on methotrexate and prednisolone presented with severe community acquired pneumonia. Intravenous trimethoprim/ sulfamethoxazole (bactrim) and high dose hydrocortisone for Pneumocystis carinii pneumonia were commenced. She developed pulmonary haemorrhage 2 weeks later and bronchoalveolar lavage cytology revealed helminthic larvae identified as strongyloides. TREATMENT AND OUTCOME: Despite treatment with ivermectin and albendazole with rapid tailing down of hydrocortisone, she succumbed to her illness. CONCLUSIONS: Strongyloides hyperinfection should be considered in an immunocompromised patient on high dose corticosteroid presenting with pulmonary haemorrhage. Prognosis remains dismal as supported by our case report and current literature.
15050194 Rheumatoid arthritis in beta-thalassemic trait: clinical, serologic and immunogenetic prof 2004 Mar OBJECTIVES: To investigate the clinical, serologic, radiologic and immunogenetic characteristics of rheumatoid arthritis (RA) occurring in patients with beta-thalassemic trait as compared with RA in control patients from the same geographical area. MATERIALS AND METHODS: Twenty-eight patients with beta-thalassemic trait fulfilling the American College of Rheumatology (ACR) criteria for RA were compared with a control group of twenty-eight RA patients matched for age, sex, disease duration and place of birth. Clinical and routine laboratory assessment, including anti-keratin antibodies and anti-citrullinated peptide antibodies, was carried out in the two groups. The patients were also evaluated for HLADRB1 alleles and radiologic damage. RESULTS: No differences were found with regard to clinical indexes of disease activity, laboratory parameters, and joint erosions. The immunogenetic analysis did not show any significant difference, the percentage of patients with alleles encoding for the shared epitope being similar in the two groups (61% vs. 57%). As for the extra-articular features, we found a trend for a lower prevalence of sicca syndrome in the beta-thalassemic group (14% vs. 39%; P = 0.06). Rheumatoid nodules were not found in beta-thalassemic patients while they were present in two RA patients in the control group. CONCLUSIONS: The chronic polyarthritis occurring in beta-thalassemic trait carriers can be regarded as a true RA similar to that found in Mediterranean countries, possibly characterized by a low prevalence of extra-articular features.
11960310 The IDDM13 region containing the insulin-like growth factor binding protein-5 (IGFBP5) gen 2002 Apr We considered that the constitutive over-expression by cultured rheumatoid arthritis (RA) fibroblast-lineage synoviocytes of genes like IGFBP5 could indicate new candidate susceptibility genes. IGFBP5 is located in a region where an insulin-dependent diabetes mellitus (IDDM) susceptibility locus, IDDM13 (2q33-q36), has been mapped. Previous evidence that non-MHC IDDM loci overlap RA susceptibility loci made IGFBP5 and its region an interesting candidate locus which was tested for linkage. Forty-nine sibships (2-4 affected siblings per sibship) with RA were genotyped with microsatellite markers covering an 11.2 cM interval in the IGFBP5/IDDM13 region. Both the two-point LOD scores and a 'nonparametric' allele-sharing analysis revealed no evidence for linkage (max LOD = 0.54, P = 0.5, respectively). Adjustments for the presence of 'shared-epitope' alleles did not significantly change the LOD scores. These results suggest that, despite the involvement of the 2q33-q36 chromosomal region in another organ-specific autoimmune disease, it is unlikely that this region harbors a RA susceptibility locus.
15334453 Increased levels of C-reactive protein in serum from blood donors before the onset of rheu 2004 Aug OBJECTIVE: We previously reported that approximately half of the patients with rheumatoid arthritis (RA) have specific serologic abnormalities (elevated serum concentrations of IgM rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies) starting several years before the onset of symptoms. In this study, the presence of serologic signs of inflammation in patients with preclinical RA was investigated with serial measurements of C-reactive protein (CRP). METHODS: Seventy-nine patients (61% female; mean age at onset of symptoms 51 years) who had been blood donors before the onset of RA were identified. Frozen serum samples from each donor were retrieved, together with 1 sample from a control donor matched for age, sex, and date of donation. CRP was measured using a highly sensitive latex-enhanced assay. The dates of donation were categorized into 15 1-year periods preceding the onset of RA symptoms. For each period, the median CRP levels in the patient and control groups were compared using the Mann-Whitney U test. The course of CRP concentrations over time in the patient group was estimated with random coefficient analysis. RESULTS: A median of 13 samples (range 1-51) per patient were available; the earliest donation was made a median of 7.5 years (range 0.4-14.5 years) before the onset of symptoms. A total of 1,078 patient samples and 1,071 control samples were tested. For all 1-year periods, the median CRP concentration was increased in the patient group compared with the control group, but this difference was statistically significant only for the periods 0-1 year, 1-2 years, and 4-5 years before the onset of symptoms. The CRP concentration increased significantly over time in patients with preclinical RA; levels were slightly higher in the group of patients who had serologic abnormalities before the onset of symptoms than in those without such serologic abnormalities. CONCLUSION: After observing specific serologic abnormalities 5 years before the onset of RA symptoms, we now report increased levels of CRP in blood donors in whom RA later developed; these increases were most common within the 2 years before the onset of symptoms. The preclinical increase in CRP levels was observed both in donors with and in those without serologic abnormalities.
15505320 MRI of large intraosseous lesions in patients with inflammatory arthritis. 2004 Nov OBJECTIVE: The purpose of our study was to evaluate on MRI the occurrence of large cystlike intraosseous lesions in patients with inflammatory arthritis. SUBJECTS AND METHODS: We prospectively reviewed contrast-enhanced MR images of 128 hands and wrists in 44 patients with clinical presentation of inflammatory arthritis. Large lesions (> or = 1 cm) found on MR images were further evaluated for the presence of a cortical break and intraarticular extension. These data were correlated with clinical and laboratory findings and the duration of arthritis. RESULTS: We found 26 patients with rheumatoid arthritis, seven with psoriatic arthritis, two with systemic lupus erythematosus, one with HIV-associated arthritis, one with mixed connective tissue disorder, one with paraneoplastic-associated arthritis, one with inflammatory bowel disease arthritis, and five patients with early unclassified inflammatory arthritis. Twelve patients had 16 large intraosseous lesions, none of which were detected on available radiographs (availability of radiographs for large erosions was 75%). A cortical break with intraarticular extension of the large lesions was seen in 12 cases. Four lesions were not intraarticular. CONCLUSION: Even large intraosseous lesions may be occult on radiography. MRI is a superior technique for detecting these lesions in the small joints of the hand and wrist in inflammatory arthritis. Although large intraosseous erosions often communicate with joints, we observed four large purely intraosseous enhancing lesions without intraarticular connection. Patients with large erosions have a longer duration of inflammatory arthritis.
12715413 Assessing the value of rheumatoid arthritis treatment alternatives: the potential effect o 2003 Mar Early intervention with drugs that delay structural damage from rheumatoid arthritis may limit disability and reduce the high costs associated with advancing disease. However, conventional agents have a potential for significant toxicities, which require monitoring that confers additional treatment costs. A new class of drugs has been developed: biologic response modifiers, two of which--etanercept and infliximab--inhibit tumor necrosis factor, a pivotal regulator of inflammation, and delay arthritic progression. Managed care organizations should encourage early diagnosis of rheumatoid arthritis, referral to a rheumatologist, and treatment with agents that reduce the overall costs of this debilitating disease.
12942698 Serum matrix metalloproteinase 3 levels in comparison to C-reactive protein in periods wit 2003 Jul OBJECTIVE: To evaluate serum matrix metalloproteinase 3 (MMP-3) levels in comparison to C-reactive protein (CRP) in periods with and without progression of radiological damage in patients with early rheumatoid arthritis (RA). METHODS: Thirty-two patients with RA and radiological progression (> or = 5 points according to the Sharp/van der Heijde method) during 6 months followed by a 6-month period without radiological progression (< or = 1 point) were selected from a prospective follow-up study of early RA patients. Serum MMP-3 levels, CRP, the erythrocyte sedimentation rate (ESR), disease activity index (DAS), swollen joint count (SJC), tender joint count (TJC), and Ritchie articular index (RAI) were measured monthly and results were transformed into mean values for the 6-month periods. RESULTS: During the period with radiological progression the mean serum MMP-3 correlated significantly with the mean CRP (r = 0.68, p < 0.001), ESR (r = 0.54, p = 0.001) and swollen joint count (r = 0.48, p = 0.006). In the period without radiological progression the mean serum MMP-3 only correlated with the mean CRP (r = 0.44, p = 0.012). Individual changes--expressed in percentages (%)--between the two periods showed a decrease in both the mean serum MMP-3 and CRP in 19 and an increase in 3 patients, in parallel with other markers of disease activity in these patients (69% of cases). The individual change (%) in mean serum MMP-3 or CRP did not correlate with the difference in radiological progression between the two periods. CONCLUSIONS: Serum MMP-3 and CRP are closely related and there seems to be no difference between serum MMP-3 and CRP with regard to the monitoring of the progression of radiological damage.
12465140 Metacarpophalangeal arthroplasty in rheumatoid arthritis: what determines satisfaction wit 2002 Dec OBJECTIVE: In patients with rheumatoid arthritis (RA), it is unclear what determines satisfaction with metacarpophalangeal (MCP) joint replacement surgery. Previous studies have focused primarily on objective outcomes, such as range of motion (ROM) or strength, although some subjective measures have been examined. We investigate which outcomes most strongly correlate with patient satisfaction. METHODS: We assembled a retrospective cohort of 26 RA patients who received a total of 160 MCP silastic spacer implants. Patients answered a telephone survey, and 18/26 patients were examined. The strength of association between specific outcome variables and patient satisfaction with surgery was measured using Spearman correlations. RESULTS: Patients had a mean age of 64.8 years and 77% were female. The mean time since surgery was 5.5 years. The strongest determinant of patient satisfaction was postoperative hand appearance (Spearman r > or = 0.60). Pain was also highly correlated with satisfaction with surgery (Spearman r > or = 0.46). Ability to perform activities of daily living and portions of the Jebsen Hand Function Test were moderately correlated with patient satisfaction. Most other measures of hand strength and ROM showed only minimal correlation with patients' overall satisfaction with surgery. CONCLUSION: Overall satisfaction with silastic spacer surgery in this cohort of RA patients was most influenced by postoperative hand appearance and by pain. While objective measures of surgical outcomes are valuable reflections of technical success, they are not important determinants of patient satisfaction. The criteria used to assess MCP arthroplasty results should be revised to better capture the outcomes that appear to matter most to patients.
12913926 Intraarticular release and accumulation of defensins and bactericidal/permeability-increas 2003 Aug OBJECTIVE: Defensins and bactericidal/permeability-increasing protein (BPI) are the components of the azurophilic granules of polymorphonuclear cells (PMNC) maintaining antimicrobial protection. Both these substances have been suggested to interact with the host immune system rather than merely kill invading pathogens. We assessed concentrations of BPI and a-defensins in synovial fluid (SF) and matching blood samples of patients with rheumatoid arthritis (RA). METHODS: Matching samples of SF and blood were collected from 67 patients with RA (aged 21-73 yrs) with acute joint effusion. Blood samples from 22 healthy individuals made up a control group. Concentrations of BPI and human neutrophil peptides (HNP 1-3) were measured by ELISA. The results were related to radiological signs of destructive arthritis, duration of the disease, and laboratory markers of inflammation. RESULTS: BPI and HNP concentrations in SF were 10-60 times higher than in matching blood samples (p < 0.0001). Strong correlations between BPI and HNP concentrations were found in both blood and SF. In SF, BPI and HNP concentrations correlated to white blood cell (WBC) count (p < 0.001), and were associated with erosive joint disease (p < 0.05). In contrast, WBC count, serum C-reactive protein, or rheumatoid factor were not significantly correlated to the BPI or HNP concentrations. Serum BPI concentrations were moderately but significantly increased in RA patients compared in blood to controls (p < 0.05). CONCLUSION: BPI and HNP are accumulated in the synovial cavity of patients with RA. Significant correlation between joint erosion and local occurrence of BPI and HNP suggests participation of these molecules in regulation of the destructive course of RA.
14969071 DMARD use in early rheumatoid arthritis. Lessons from observations in patients with establ 2003 Sep The concept of early and aggressive therapy of rheumatoid arthritis (RA) has been well documented in the past years. It includes immediate DMARD institution after diagnosis, the use of the most effective DMARDs, and rapid switching of regimens if a level of disease activity close to remission is not achieved. In this review we briefly explore to what degree this new concept has been implemented in routine clinical care. Based on an observational dataset comprising 3342 DMARD courses, we present evidence of a change in DMARD patterns in newly diagnosed RA patients towards a higher prescription rate of more aggressive drugs like methotrexate (MTX), as well as a decreasing lag time until MTX was instituted in RA patients over the years. One consequence of recent changes in therapeutic strategies is that comparative analyses of formerly versus recently employed DMARDs will be considerably biased in observational studies. By contrast to changes in DMARD usage, survey data show neither a shortening of referral time nor a change in the approach to diagnose early RA. These data indicate a need for more dissemination of the early arthritis concept.
14673986 Suppression of osteoclastogenesis in rheumatoid arthritis by induction of apoptosis in act 2003 Dec OBJECTIVE: To examine the suppressive effect of anti-human Fas monoclonal antibody (mAb) on osteoclastogenesis in rheumatoid arthritis (RA) both in vitro and in vivo. METHODS: For in vitro analysis, activated CD4+ T cells derived from peripheral blood mononuclear cells were left untreated or were treated with humanized anti-human Fas mAb (R-125224) and cocultured with human monocytes. On day 12, the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells was counted. For in vivo analysis, tissue derived from human RA pannus was implanted with a slice of dentin subcutaneously in the backs of SCID mice (SCID-HuRAg-pit model). R-125224 was administered intravenously once a week for 3 weeks. The implanted tissue and dentin slice were removed, and the pits formed on the dentin slice were analyzed. RESULTS: In vitro, coculture of activated CD4+ T cells and peripheral monocytes induced osteoclastogenesis. The number of TRAP-positive multinucleated cells was reduced when activated CD4+ T cells were treated with R-125224. We established a new animal model for monitoring osteoclastogenesis, SCID-HuRAg-pit. We found that with R-125224 treatment, the number of pits formed on the implanted dentin slices was significantly reduced and the number of lymphocytes in the implanted RA synovial tissue was dramatically reduced in this model. CONCLUSION: This is the first study to demonstrate the suppressive effect of anti-human Fas mAb on osteoclastogenesis in RA synovial tissues through the induction of T cell apoptosis. Induction of apoptosis of infiltrated lymphocytes could be a useful therapeutic strategy for RA, in terms of suppressing both inflammation and bone destruction.
12746895 Epstein-Barr virus load in the peripheral blood of patients with rheumatoid arthritis: acc 2003 May OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) have elevated Epstein-Barr virus (EBV) load in their peripheral blood mononuclear cells (PBMCs) and whether it is correlated with the HLA-DR genes they express, we developed an accurate EBV DNA quantitative assay using real-time polymerase chain reaction (PCR) with fluorescent probes. METHODS: We studied the EBV DNA load in the PBMCs of 84 patients with RA, 69 normal controls, and 22 patients with rheumatic conditions other than RA. A 214-bp segment from the long internal repeat of EBV was amplified from 500 ng of PBMC DNA (150,000 cells) and quantified by real-time PCR with fluorescent probes. RESULTS: We demonstrated that in patients with RA, the EBV DNA load in PBMCs is increased almost 10-fold compared with that in normal controls. The EBV load is stable over time and is not obviously influenced by disease-modifying antirheumatic drugs or HLA-DR. CONCLUSION: Patients with RA have elevated EBV load in their peripheral blood.