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ID PMID Title PublicationDate abstract
10102645 Distribution of TNF-alpha, TNF-R55 and TNF-R75 in the rheumatoid synovial membrane: TNF re 1999 Mar The expression of TNF-alpha and its receptors in the rheumatoid synovial membrane was investigated using immunohistochemistry and immunocytofluorescence. TNF-alpha+ cells (< 10% of all cells) were found in all regions, predominantly in sublining and diffuse infiltrates. The highest percentage of TNF-R+ cells was found in the lining layer (50-90%), with a slight predominance of TNF-R55. In the sublining, fewer cells expressed TNF-R (approximately 50%), mostly TNF-R75. TNF-R75+ cells were also detectable in diffuse infiltrates and lymphoid aggregates (10-50%). These contained only individual TNF-R55+ cells. In diffuse infiltrates, there were slightly more TNF-R55+ cells than in lymphoid aggregates (in both cases < 10%). In sequential sections, TNF-alpha+ cells localized mostly in the vicinity of TNF-R+ cells. Macrophage-like cells appeared to be the predominant TNF-R+ cell type. CD3+ T cells in lymphoid aggregates expressed exclusively TNF-R75. Subsequently, the expression of membrane-bound TNF-alpha, TNF-R55 and TNF-R75 was tested by FACS analysis in isolated RA synoviocytes (n = 7 patients). Only four specimens expressed mTNF-alpha, and that on a low percentage of cells (2 +/- 2.4%; mean +/- SD). In contrast, all specimens expressed higher percentages of TNF-R55 and TNF-R75 (21 +/- 1% and 14 +/- 7.1%, respectively). These results demonstrate that: (1) the percentage of cells expressing soluble/transmembrane TNF-alpha is greatly outnumbered by the percentage of cells expressing TNF receptors; and (2) TNF-alpha-expressing cells are localized in regions expressing substantial levels of TNF receptors. Therefore, the known pro-inflammatory and pro-arthritic effects of TNF-alpha are probably mediated by local interactions between the receptors and their soluble and transmembrane ligands.
10227806 Neutrophilic myeloperoxidase-macrophage interactions perpetuate chronic inflammation assoc 1999 May Rheumatoid arthritis is a systemic disease of unknown etiology. The purpose of this study was to elucidate an unrecognized interaction between neutrophilic myeloperoxidase (MPO) and macrophages (Mphi) which could perpetuate the inflammatory response associated with arthritis. A monoarticular arthritis was induced by intra-articular injection of group A streptococcus cell wall fragments (PG-APS) into the ankle joint of female Lewis rats. After swelling/erythema subsided, joints were reinjected with either recombinant MPO or enzymatically inactive MPO (iMPO). Joint measurements were made daily and arthritis was confirmed by histology. Neither iMPO nor MPO could initiate "clinical" arthritis; however, either form of the enzyme injected after PG-APS induced a dose-dependent increase in erythema and swelling. Mannans, which block the binding of MPO to Mo, ablated clinical symptoms. Also, the presence of tumor necrosis factor alpha was observed only in diseased joints using immunocytochemistry.
11014342 The course of radiologic damage during the first six years of rheumatoid arthritis. 2000 Sep OBJECTIVE: To describe the radiologic course in a large cohort of patients with early rheumatoid arthritis (RA) and to analyze individual components of damage. METHODS: Five hundred two patients with recent-onset RA (disease duration <1 year) underwent annual radiologic assessment for a maximum of 6 years in this longitudinal prospective study. The study was designed to investigate the efficacy of 3 different therapeutic strategies. For the assessment of radiologic damage, radiographs of the hands and feet were scored according to the modified Sharp/van der Heijde method (SHS; range 0-448). A mean of 2.9 (range 1-7) radiographs was read per patient. RESULTS: Stable rates of progression of the SHS, erosion score, and narrowing score were found over the course of RA: the mean rates were 8.6, 5.4, and 3.2 modified Sharp units per year, respectively. The rate of progression of newly (not previously) damaged joints declined, and the rate of progression of already damaged joints (which became more damaged) increased during followup, leading to an equal contribution to progression of the SHS at 5 years. The joints of the feet, especially the fifth metatarsophalangeal joint, generally became eroded earlier and more of them became eroded compared with the joints of the hands. CONCLUSION: Radiologic damage progresses at a constant rate. In advanced disease, monitoring the progression of previously existing damage is as important as assessing new abnormalities in previously undamaged joints. Radiographs of the feet should be included in assessments of radiologic damage that are used in clinical intervention trials and daily practice.
10955344 Measuring the epidemiology of distress: the rheumatology distress index. 2000 Aug OBJECTIVES: (1) To examine clinical and psychological variables to determine which are associated with psychologic and psychosocial severity or "distress"; (2) to investigate whether patients with the 2 major rheumatic disorders, rheumatoid arthritis (RA) and osteoarthritis (OA), differ in distress variables and distress; and (3) to develop and validate a simple, clinically acceptable index of distress suitable for routine care and research purposes. METHODS: A total of 2,403 patients were evaluated in 2 data sets (N = 1,399 and N = 1,490). The first data set was evaluated in the clinic by a routine clinical examination and administration of the Clinical Health Assessment Questionnaire (CLINHAQ). This instrument includes measures of pain, global severity, functional disability, anxiety, depression, sleep disturbance, fatigue, health satisfaction, and health status. The second data set was evaluated by a mailed questionnaire that included the CLINHAQ, but also coping scales, the Beliefs in Pain Control Questionnaire, the Self Performance Scale, and the Arthritis Helplessness Index. RESULTS: RA and OA groups had similar scores for the variables associated with distress: pain, global severity, functional disability, anxiety, depression, sleep disturbance, fatigue, health satisfaction, and health status. Patients with fibromyalgia (FM) had more abnormal scores for every variable, reflecting overall distress. Using patients with FM as a "gold standard" of distress, we developed an index in data set 2. the Rheumatology Distress Index (RDI), made up of 5 variables, anxiety, depression, global severity, fatigue, and sleep disturbance, that best identified patients with FM compared to other patients. We then validated the instrument on the distress severity clusters formed in data set 1. The correlation between RDI and distress severity cluster was 0.874 with all patients considered and 0.867 with FM patients excluded. In addition, RDI predicted 1,174 of 1,399 (83.9%) cluster memberships correctly. Compared with a battery of psychological and clinical tests that classified 74% of FM and non-FM patients correctly, the RDI and is only slightly less effective, classifying 70.3% correctly. CONCLUSION: Distress is a patient rather than a disease phenomenon. A simple, easy to administer self-report questionnaire can be used to classify patients according to their level of distress. The resulting index, the RDI. accurately identifies distressed and non-distressed patients. Such an index should be useful for patient care and research.
11426026 Osteoclast-like cells in an in vitro model of bone destruction by rheumatoid synovium. 2001 Jun OBJECTIVE: Osteoclasts may be involved in the process of rheumatoid bone destruction. To test this hypothesis, we developed an in vitro model of bone destruction by osteoclast-like cells derived from cultured rheumatoid synovial tissue without using any inducers. METHODS: Synovial tissues were obtained from rheumatoid arthritis and osteoarthritis patients and tissue pieces of about 2 mm(3) that contained synovial lining were cultured. Multinucleated cells derived from cultured synovial tissues were studied cytochemically and morphologically for osteoclast-specific markers. RESULTS: Fibroblast-like and macrophage-like cells from the tissue pieces proliferated in the coexistence of lymphocytes. After 14 days of culture, multinucleated cells with tartrate-resistant acid phosphatase activity appeared. These cells expressed vacuolar H(+)-ATPase, the vitronectin receptor and cathepsin K. Although binding of (125)I-labelled salmon calcitonin was very low, the cells contained ringed structures of F-actin and showed strong bone-resorbing activity on ivory slices. Proliferation of macrophage-like cells and formation of multinucleated cells continued during 6 months of culture in the presence of fibroblast-like cells. The bone-resorbing activity of multinucleated cells derived from rheumatoid synovial tissue was much higher than that of cells from osteoarthritis synovial tissue, and was related to the disease activity of rheumatoid arthritis. CONCLUSION: Our culture system reproduced in vitro the process of bone destruction by rheumatoid synovium, including the proliferation and fusion of precursor cells, polarization, activation and bone tissue resorption. This system may provide a tool for understanding the mechanisms of bone destruction in rheumatoid arthritis and for the development of new therapies to prevent bone destruction.
11178946 Up-regulation and differential expression of the hyaluronan-binding protein TSG-6 in carti 2001 Jan OBJECTIVE: TSG-6 [the product of tumor necrosis factor (TNF)-stimulated gene-6] is a hyaluronan-binding protein that is present in the synovial fluids of arthritis patients and is secreted by cells of articular joints (e.g. chondrocytes and synoviocytes). This study examines the pattern of TSG-6 expression in normal and diseased cartilage and synovium using immunohistochemical techniques. DESIGN: A polyclonal antibody was raised against recombinant Link module from human TSG-6 and used to detect the protein in tissue sections taken from osteoarthritis (OA) and rheumatoid arthritis (RA) patients and controls. RESULTS: There was no TSG-6 detected in normal tissues. In all OA synovium there was intense TSG-6 expression throughout the intimal layer, whereas in RA staining in this region was generally less pronounced and was absent at the synovial surface in tissues exhibiting significant inflammation. In RA TSG-6 was also expressed by infiltrating leukocytes and by cells at the cartilage-synovium pannus junction. TSG-6 immunoreactivity was present in the tunica intima of blood vessels in OA subintima, being particularly noticeable in the thickened smooth muscle of inflamed vessel walls, but was mostly confined to the lumen of the vessel in RA. In cartilage the majority of chondrocytes expressed TSG-6 in both OA and RA, usually with extensive staining in the surrounding matrix. CONCLUSION: TSG-6 is present within synovium and cartilage of arthritic joints, but not normal controls, and is synthesized by the resident cells. The pattern of TSG-6 expression is consistent with its proposed roles in extracellular matrix (ECM) remodeling and cellular proliferation.
9550475 Quantitative microscopic analysis of inflammation in rheumatoid arthritis synovial membran 1998 Apr OBJECTIVE: To evaluate microscopic measures of inflammation in rheumatoid arthritis synovial tissue samples selected at arthroscopy compared with those obtained blindly by needle biopsy from the suprapatellar pouch (SPP) of the same joint. METHODS: Samples were selected at knee arthroscopy from the SPP and the lateral and medial gutters. Immediately following arthroscopy, a biopsy needle was inserted through the same portal into the SPP by a second investigator, and 3 further samples were obtained blindly. Using standard immunohistologic methods, all samples were analyzed by a single investigator without knowledge of the original tissue location and biopsy technique. Following staining with anti-CD3 and anti-CD68 monoclonal antibodies, T lymphocyte and macrophage infiltration were measured by quantitative analysis. RESULTS: Synovial tissues from 14 patients were analyzed. In comparing microscopic measures of inflammation using the 2 procedures, mean scores of lining cell depth and the percentage of CD68+ cells in the lining layer correlated positively (tau = 0.59, P = 0.003 and tau = 0.73, P = 0.0003, respectively). In the sublining layer, CD3+ cell counts also correlated significantly (tau = 0.71, P = 0.0004). Sublining CD68+ cell counts did not correlate. This was explained by the observation that CD68+ cell infiltration in areas adjacent to articular cartilage was significantly greater than in the SPP (P = 0.01), suggesting preferential trafficking to this site by macrophages, but not by T lymphocytes. Macroscopic appearance at arthroscopy did not predict microscopic features. CONCLUSION: Most microscopic measures of inflammation in synovial tissue samples obtained blindly from the SPP were similar to those determined in samples selected at arthroscopy. However, measurements in samples from the SPP may underestimate the intensity of macrophage infiltration in areas more adjacent to cartilage. These observations have important implications for future study of macrophage function in synovial tissue.
10875318 Weak androgen levels, glucocorticoid therapy, and bone mineral density in postmenopausal w 2000 OBJECTIVE: To study dehydroepiandrosterone sulfate (DHEAS) and androstenedione (AND) status in postmenopausal women with rheumatoid arthritis (RA), the effects of glucocorticoid therapy on DHEAS and AND levels, and their relationship with bone mineral density (BMD). METHODS: Forty-six postmenopausal women with RA were separated into two groups based on whether they had a negative history for glucocorticoid therapy (n = 24) or were currently on glucocorticoid therapy (n = 22). The control group was composed of 39 postmenopausal women who had never received hormone replacement therapy. Serum DHEAS and AND levels were measured using a radioimmunoassay. BMD was determined at the lumbar spine (L2-L4) and femoral neck using a DEXA Hologic QDR-1000 densitometer. Results. RA patients and controls were similar in age, weight, body mass index, and years since menopause. DHEAS and AND levels were lower in the glucocorticoid-treated RA group than in the other two groups. The glucocorticoid-treated RA group also had a significantly lower femoral BMD value than the nonglucocorticoid-treated RA group. Lumbar BMD was similar in the two RA groups and in the controls. CONCLUSION: Decreases in DHEAS and AND levels in postmenopausal women with RA are probably related to glucocorticoid therapy rather than to the disease itself.
9117175 Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. 1997 Jan The objective was to analyse whether the activity of the cytochrome P450 isoenzyme CYP3A4 is altered by disease activity of rheumatoid arthritis (RA). Urinary 6 beta-hydroxycortisol excretion, expressed as a fraction of the urinary creatinine output, was measured in 21 patients with RA treated with three different disease-modifying anti-rheumatic drugs (DMARDs) over 24 weeks. There were no correlations between urinary 6 beta-hydroxycortisol/creatinine (6 beta-OHC/Creat) ratio and measurements of disease activity such as plasma viscosity, Ritchie articular index and early morning stiffness. In addition, the three DMARDs sulphasalazine, sodium aurothiomalate and D-penicillamine, smoking and the intake of various CYP3A4 substrates had no consistent detectable effect on the 6 beta-OHC/Creat ratio. There is no evidence that the dosage of drugs metabolized by the CYP3A4 isoenzyme needs to be adjusted for disease activity in RA.
10591975 [Lesional pattern and clinical symptoms in rheumatoid flexor tendon disease]. 1999 Oct OBJECTIVES: To assess complaints and clinical findings of rheumatoid hand flexor tendon disease in relationship to the anatomical site and the type of lesion in order to improve the diagnosis and enable early operative treatment with preservation of hand function. METHODS: 123 patients of the hands of 78 patients (66 female, 12 male) with a mean age of 57 years were analyzed retrospectively. Preoperative complaints and clinical findings were recorded according to their frequency. Three different types of flexor tendon disease were distinguished intraoperatively: isolated tenosynovitis, tenosynovitis with tendon lesion, and complete tendon rupture. RESULTS: 188 tendons showed isolated synovitis, 208 had a tendon lesion with synovitis, and 30 tendons a rupture. Tenosynovitis was found in the palm and wrist mainly. The 2nd, 3rd and 4th finger were most frequently involved. 81 tendon adhesions, 12 nodules, 63 superficial lesions and 52 defects were detected. These lesions were found mainly in the palm and the second and third ray. The profundus tendon was affected most often. Ruptures were detected most often in the wrist caused by bony spurs and tenosynovitis. A clinical difference between tenosynovitis with and without tendon lesion was not found. However, complaints and findings were different in the digit, palm, wrist and forearm. Ruptures had characteristic clinical findings. CONCLUSIONS: Rheumatoid flexor tendon disease is common. Tenosynovitis is often accompanied by tendon lesions. Ruptures occur as disease progresses. Exact assessment of complaints and clinical findings is mandatory to diagnose and localize flexor tendon disease. Early operative intervention helps to preserve the function of the hand.
9228123 Role of HLA-DR-DR and DR-DQ associations in the expression of extraarticular manifestation 1997 Jul OBJECTIVE: To investigate the role of HLA-DRB1 genotypes and HLA-DRB1*0401-DQB1*03 haplotypes in the expression of extraarticular manifestations and rheumatoid factor (RF) in rheumatoid arthritis (RA). METHODS: 189 patients with RA were classified according to the presence of vasculitis and seropositivity for RF. IgM RF were determined by at least 2 of the following methods: standard latex agglutination, the Waaler-Rose test, and nephelometry. HLA genotyping was performed by reverse dot blot hybridization for DRB1 alleles and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for DQB1 alleles. RESULTS: The QKRAA susceptibility sequence, which characterizes the HLA-DRB1*0401 allele, was observed in 71.5% of the 21 patients with vasculitis and 57.6% of the 158 RF positive patients. The influence of a 2nd allele within the major histocompatibility complex was observed but the allele differed according to the clinical features examined. Higher risk for vasculitis was observed in patients who carried 2 DRB1 susceptibility alleles, one characterized by the QKRAA sequence and the other by the QRRAA sequence (OR = 3). Conversely, the higher risk for IgM RF positivity was observed in patients who carried the QKRAA sequence of the DRB1 alleles with the DQB1*0301 alleles of the DQ region (OR = 4.7). CONCLUSION: Our data suggest that a distinct immunogenetic association is involved in the extraarticular manifestations of RA and in the expression of RF.
9684082 Pedal manifestations of musculoskeletal disease. 1998 Jul The major systemic musculoskeletal diseases that involve the foot include the inflammatory arthritides, gout, and diabetic osteoarthropathy. Podiatric problems are present in over one-third of patients with musculoskeletal disease and in over half of all patients with diabetes. The pedal manifestations of musculoskeletal disease are reviewed as the first indicators of systemic disorders and as they occur in established systemic diseases.
9559334 Cyclosporin A and FK-506 inhibit development of superantigen-potentiated collagen-induced 1998 May 1. Staphylococcal enterotoxine B (SEB; superantigen) accelerated the onset of arthritis in mice preimmunized with type II collagen (SEB-potentiated collagen-induced arthritis). Cyclosporin A and FK-506 inhibited the induction and development of clinical signs and histopathological changes of SEB-potentiated collagen-induced arthritis in mice. 2. Simultaneously, both cyclosporin A and FK-506 inhibited the development of humoral and cellular immunity to type II collagen. 3. The expression of IL-2 receptor (CD25) by SEB on splenocyte T cells from collagen-preimmunized mice was inhibited by both agents in ex vivo experimentation.
10868016 [Long-term outcome of metatarsal head resection in rheumatoid arthritis]. 2000 Apr Between January 1983 and December 1987, metatarsal head-resections were performed on 203 patients, comprising a total of 370 feet, using the Hueter/Mayo and Hoffmann procedure. Seventy-two patients, comprising a total of 126 feet, were available for post-operative review after an average of 11.4 years from the date of the original operations. The information obtained from standardized questionnaires was compared to the information found in each patient's file. In addition, every available pre- and post-operative x-ray taken from 1983 to 1987 was analyzed. Thus, with an average follow-up period of 5.6 years, the changes found in the pre- and post-operative x-rays from a total of 183 feet could be compared. Before the operations, nearly 100% of the examined feet suffered from painful synovial hypertrophy and erosion of the metatarsophalangeal joints with dislocation and subluxation, causing approximately 70% of all patients to have great difficulties in walking. After the operations, however, 90.2% of the patients reported that this condition had noticeably improved or had completely disappeared. In fact, 87.5% of all patients reported a lasting improvement in their ability to walk longer distances. As the main criteria in determining the success of an operation (namely, the noticeable reduction of pain and increased mobility) were achieved in 87.5% of the patients, we consider the metatarsal head-resection a reliable method of correcting forefoot deformities in rheumatoid arthritis.
10437187 Therapeutic effects of the instant rheumatoid medicinal granules for treatment of acute rh 1997 Sep The Instant rheumatoid medicinal granules (IRMG [symbol: see text]) is a proprietary drug for oral administration after being dissolved in boiled water. It consists of the herbs for clearing away heat, detoxifying, eliminating dampness, promoting flow of qi, invigorating blood circulation and relieving pain, used for treatment of acute rheumatoid arthritis. Of the 34 cases treated, 5 cases were clinically cured, and 15 cases markedy effective, the total effective rate being 91.23%. IRMG also showed certain action on immune regulation.
9125243 Immunogenetic similarities between patients with Felty's syndrome and those with clonal ex 1997 Apr OBJECTIVE: Patients with chronic clonal proliferation of large granular lymphocytes (LGL leukemia) often have splenomegaly, neutropenia, and rheumatoid arthritis (RA), thereby resembling the manifestations observed in patients with Felty's syndrome. The present study sought to determine whether patients with these disorders represent 2 distinct subsets of neutropenic RA. METHODS: Prospective cohort study of outpatients attending clinics in university and private hospitals and in offices of private practice physicians. Twenty-two patients with Felty's syndrome and 22 patients with LGL leukemia, 10 of whom had RA, were studied. HLA genotyping was performed on peripheral blood mononuclear leukocyte genomic DNA. RESULTS: Nineteen of the 22 patients with Felty's syndrome (86%) were DR4 positive. Nine of the 10 patients with LGL leukemia plus RA were also DR4 positive. In contrast, only 4 of the 12 patients with LGL leukemia without RA (33%) were DR4 positive, a frequency that was within the normal range. CONCLUSION: The finding of an equally high prevalence of DR4 in patients with Felty's syndrome and in those with LGL leukemia plus RA suggests that both disorders have a similar immunogenetic basis and are parts of a single disease process rather than 2 separate disorders.
10505523 Total elbow arthroplasty with use of a nonconstrained humeral component inserted without c 1999 Sep BACKGROUND: Most total elbow prostheses that are currently in use require cement for fixation of each component. We developed a new (type-5) prosthesis that does not need cement for fixation. METHODS: The humeral component is made of cobalt-chromium alloy, and its stem is porous-coated with a plasma spray of titanium alloy. There are two options for the ulnar component: an all-polyethylene type and a metal-backed type with a porous-coated stem. Forty-three elbows in thirty-seven patients who had rheumatoid arthritis were treated with total elbow replacement arthroplasty with use of the type-5 prosthesis. The humeral component was implanted without cement in all elbows, whereas the ulnar component was implanted without cement in eleven elbows and was fixed with cement in the remaining thirty-two. The elbows were followed for an average of three years and ten months (range, two years and six months to five years and six months). RESULTS: The clinical results were assessed according to a modification of the Mayo Clinic Performance Index. At the time of the latest follow-up, the overall result was excellent for six elbows, good for thirty-one, and fair for six. All elbows had been rated as poor before the operation. There was almost complete relief of pain in twenty-nine elbows and mild or occasional pain in the remaining fourteen. Flexion increased markedly, from an average of 104 degrees preoperatively to an average of 133 degrees postoperatively; this difference was highly significant (p < 0.001, Student t test). In contrast, extension (flexion contracture) worsened slightly, from an average of 38 degrees preoperatively to an average of 42 degrees postoperatively; this difference was significant (p < 0.05). There was one postoperative dislocation of the elbow, and ectopic bone formed in another, with recurrence of ankylosis. Both elbows had a reoperation, and a good result eventually was obtained. There were no instances of postoperative infection or neuropathy of the ulnar nerve. Radiographically, there were no radiolucent lines at the bone-metal interface of any of the humeral or ulnar stems that had been implanted without cement, suggesting solid fixation by osseointegration. CONCLUSIONS: The results of total elbow arthroplasty with use of this prosthesis appear promising. There was a high rate of relief of pain as well as of restoration of adequate function in patients in whom the elbow was severely affected by rheumatoid arthritis.
11056669 Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset. 2000 STATEMENT OF FINDINGS: An inception cohort of 238 patients having peripheral joint synovitis of less than 12 months duration was evaluated clinically and followed prospectively for 1 year to determine the clinical significance of a number of rheumatoid arthritis (RA) associated autoantibodies. Serum samples collected at the time of the initial evaluation were tested for rheumatoid factor (RF) and antibodies to Sa (anti-Sa), RA-33, (pro)filaggrin [antifilaggrin antibody (AFA)], cyclic citrullinated peptide (anti-CCP), calpastatin, and keratin [antikeratin antibody (AKA)]. RF had a sensitivity of 66% and a specificity of 87% for RA. Anti-Sa, AFA, and anti-CCP all had a specificity of more than 90%, but a sensitivity of less than 50% for this diagnosis. Overall, there was a high degree of correlation between AFA, AKA, anti-Sa or anti-CCP, this being highest between anti-Sa and anti-CCP (odds ratio, 13.3; P < 0.001). Of the 101 patients who were positive for at least one of these four autoantibodies, 57% were positive for only one. Finally, anti-SA identified a subset of predominantly male RA patients with severe, erosive disease. Anti-SA, AFA and anti-CCP are all specific for early RA but, overall, have little additional diagnostic value over RF alone. Although these antibodies may preferentially recognize citrullinated antigens, the modest degree of concordance between them in individual patient sera suggests that it is unlikely a single antigen is involved in generating these responses.
10898066 Increased expression of CD23 in rheumatoid synovitis. 2000 OBJECTIVE: Soluble (s)CD23 is a potent macrophage stimulator. High levels of this molecule have been reported in rheumatoid arthritis (RA) serum. We investigated the expression of CD23 and its ligands in rheumatoid synovial fluid and cells. METHODS: Levels of sCD23, and cellular expression of CD23 and its ligands CD21, CD11b, and CD11c were measured in synovial fluid (SF) of RA patients and in blood of RA patients and controls. RESULTS: SF contained higher levels of sCD23 than either rheumatoid or normal sera (median 4.8, 3.16,and 1.13 ng/ml respectively, p <0.01). Synovial CD23 was found to be expressed principally on macrophages. While little CD21 expression was detected, CD11b and CD11c were both expressed at high levels, particularly on macrophages. CONCLUSIONS: Soluble CD23 is present in high levels in RA synovial fluid. Macrophages appear to be the principal source. Macrophages also express ligands for sCD23, and may therefore also be the targets of this potent pro-inflammatory molecule.
9380731 Somatic mutations in the p53 tumor suppressor gene in rheumatoid arthritis synovium. 1997 Sep 30 The factors that regulate the perpetuation and invasiveness of rheumatoid synovitis have been the subject of considerable inquiry, and the possibility that nonimmunologic defects can contribute to the disease has not been rigorously addressed. Using a mismatch detection system, we report that synovial tissue from the joints of severe chronic rheumatoid arthritis patients contain mutant p53 transcripts, which were not found in skin samples from the same patients or in joints of patients with osteoarthritis. Mutant p53 transcripts also were identified in synoviocytes cultured from rheumatoid joints. The predicted amino acid substitutions in p53 were identical or similar to those commonly observed in a variety of tumors and might influence growth and survival of rheumatoid synoviocytes. Thus, mutations in p53 and subsequent selection of the mutant cells may occur in the joints of patients as a consequence of inflammation and contribute to the pathogenesis of the disease.