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ID PMID Title PublicationDate abstract
9741312 Influence of HLA-class II incompatibility between mother and fetus on the development and 1998 May OBJECTIVE: To assess the relation between the course of rheumatoid arthritis (RA) during pregnancy or the onset of RA postpartum and DRB1, DQA1, and DQB1 incompatibilities between mother and child. METHODS: In 45 pregnancies of 33 RA patients the course of RA was related to the number of class II incompatibilities. Furthermore class II incompatibilities in 16 pregnancies followed by RA onset were compared with those in 87 control pregnancies. RESULTS: The risk of a favourable compared with an unfavourable course was 0.95, 2.67, and 2.38 in case of DRB1, DQA1, and DQB1 incompatibility respectively. DQA1 and DQB1 incompatibilities were seen more often in the 10 pregnancies followed by RA onset within three months than in control pregnancies (OR 8.02, 95% CI 0.97, 66.06 and OR 8.79 95% CI 1.07, 72.46 respectively). CONCLUSIONS: DQA1 and DQB1 incompatibility between mother and child seems to have a favourable effect on the course of RA and may postpone the risk of RA onset during pregnancy.
11597179 DNA cytofluorometric analysis of chondrocytes in human articular cartilages under normal a 2001 Oct OBJECTIVE: Since most chondrocytes in articular cartilage are in the resting phase (G0) of the cell cycle, it has been difficult to investigate their cell kinetics using 3H-thymidine autoradiography, or immunohistochemistry. In the present study, DNA cytofluorometry, which is useful to analyse the cell kinetics even for such inactive cell populations as in the G0 phase, was applied to human chondrocytes of the articular cartilages under normal aging and pathologic conditions such as osteoarthritis (OA), rheumatoid arthritis (RA), and aseptic necrosis (AN). DESIGN: The human articular cartilages for the study were obtained from autopsy and surgical materials. Fifty joints were used for the study of aging, 54 for the study of OA, 20 for studying RA, and 10 for AN study. The isolated chondrocytes were quickly prepared from fresh articular cartilages, using a combination method of enzymatic digestion with papain and collagenase, followed by mechanical cell separation by churning and homogenization. RESULTS: The DNA histograms obtained by cytofluorometry with propidium-iodide staining showed that most chondrocytes had diploid DNA content (2c) in all cartilages studied, suggesting that they were in the G0 phase. However, there were a few chondrocytes having tetraploid DNA content (4c) in the normally aged articular cartilages, and there were some cells having DNA content between 2c and 4c in the diseased cartilages. The former cells were considered to be G0-phase cells of the 4c chondrocytes, while the latter cells were considered to be in the DNA synthetic (S) phase or G2-phase of the 2c chondrocytes. The frequency of 4c chondrocytes in aged cartilage was significantly increased, compared to that in the young cartilage. In contrast to the normal cartilage, the frequency of S- and G2-phase cells, which was expressed as the S- G2 index, in diseased cartilages (OA, RA and AN) was significantly high (P< 0.0001). In OA cartilage, the S-G2 index was much higher in the severe or moderate stage than in the mild stage, suggesting that the chondrocytes in clusters may actively proliferate. CONCLUSION: These results showed that in normal articular cartilages most chondrocytes are in the G0 phase, while some became 4c polyploid cells, and that these G0-phase chondrocytes had a potential to proliferate under diseased conditions.
10385847 Familial clustering of autoimmune disorders and evaluation of medical risk factors in auti 1999 Jun Autism is an age-dependent neurologic disorder that is often associated with autoimmune disorders in the patients' relatives. To evaluate the frequency of autoimmune disorders, as well as various prenatal and postnatal events in autism, we surveyed the families of 61 autistic patients and 46 healthy controls using questionnaires. The mean number of autoimmune disorders was greater in families with autism; 46% had two or more members with autoimmune disorders. As the number of family members with autoimmune disorders increased from one to three, the risk of autism was greater, with an odds ratio that increased from 1.9 to 5.5, respectively. In mothers and first-degree relatives of autistic children, there were more autoimmune disorders (16% and 21%) as compared to controls (2% and 4%), with odds ratios of 8.8 and 6.0, respectively. The most common autoimmune disorders in both groups were type 1 diabetes, adult rheumatoid arthritis, hypothyroidism, and systemic lupus erythematosus. Forty-six percent of the autism group reported having relatives with rheumatoid diseases, as compared to 26% of the controls. Prenatal maternal urinary tract, upper respiratory, and vaginal infections; asphyxia; prematurity, and seizures were more common in the autistic group, although the differences were not significant. Thirty-nine percent of the controls, but only 11% of the autistic, group, reported allergies. An increased number of autoimmune disorders suggests that in some families with autism, immune dysfunction could interact with various environmental factors to play a role in autism pathogenesis.
11304108 Rational use of new and existing disease-modifying agents in rheumatoid arthritis. 2001 Apr 17 Because of radiographic evidence of progressive bone loss and the inability to eliminate synovial proliferation with methotrexate, it became apparent that therapy for rheumatoid arthritis needed further advancement. Methotrexate is not a remission-inducing drug and may have dose-limiting toxicity. In the past 2 years, three new disease-modifying antirheumatic drugs (DMARDs) have been approved: leflunomide, etanercept, and infliximab. Each of these agents has demonstrated efficacy compared with placebo in randomized, controlled studies. Because methotrexate had a dominant therapeutic role, the new drugs were also studied in combination with it. Other established DMARDs, such as sulfasalazine and hydroxychloroquine, have also demonstrated efficacy when used together with methotrexate. The results of these combination studies clearly demonstrate that clinical responses can be meaningfully improved when new and existing DMARDs are added to methotrexate. Although toxicity remains a serious concern when powerful immune modulators and antimetabolites are used in combination, relatively few serious adverse events have been reported during 2-year treatment periods. It has also become apparent that combinations of new DMARDs and methotrexate virtually halt radiographic progression over 2 years. The new agents are expensive, but annual costs must be weighed against the personal and societal expense of joint arthroplasty, hospitalizations, disability, and diminished quality of life that accompanies poorly controlled rheumatoid arthritis. The ultimate value of combination DMARD therapy with methotrexate will be determined by long-term data on safety, efficacy, and effects on radiographic deterioration of bone. Additional long-term observational data on the incidence of joint arthroplasty and disability will help to place the issue of societal costs in a better perspective. This will allow the value of aggressive treatment to be established with certainty.
10338381 Antitumor necrosis factor therapy for inflammatory bowel disease: a review of agents, phar 1999 May Tumor necrosis factor-alpha (TNFalpha), a proinflammatory cytokine, plays an important role in the pathogenesis of inflammatory bowel disease (IBD). Biotechnology agents including a chimeric monoclonal anti-TNF antibody (infliximab), a humanized monoclonal anti-TNF antibody (CDP571), and a recombinant TNF receptor fusion protein (etanercept) have been used to inhibit TNFalpha activity. Controlled trials have demonstrated efficacy for infliximab in moderately to severely active Crohn's disease (CD) and fistulizing CD sufficient to justify recent U.S. Food and Drug Administration (FDA) approval. Additional trials have been completed in rheumatoid arthritis (RA). Similarly, preliminary controlled trials have suggested efficacy for CDP571 in active CD and RA. Larger controlled trials have demonstrated efficacy for etanercept in RA patients who have failed disease modifying antirheumatic drug (DMARD) therapy leading to FDA approval for RA. Toxicities observed with anti-TNF therapies have included formation of human antichimeric antibodies (HACA) with associated acute and delayed hypersensitivity infusion reactions, human antihuman antibodies (HAHAs), and formation of autoantibodies with rare instances of drug-induced lupus. Several cases of non-Hodgkin's lymphoma also has been described. Future studies should evaluate optimal timing and duration of anti-TNF therapy, the utility of adjuvant medical treatments during anti-TNF therapy, and evaluate long-term safety and efficacy of the various anti-TNF agents.
9104949 Idiopathic perniosis and its mimics: a clinical and histological study of 38 cases. 1997 Apr Perniosis is a term applied to cold-induced painful or pruritic erythematous or violaceous acral papular or nodular lesions. We examined 39 skin biopsies from 38 patients who presented with acral purpuric lesions, suggesting a diagnosis of perniosis clinically or pathologically. The presence of a systemic or extracutaneous disease was established in 17 patients, including 5 with systemic lupus erythematosus (SLE), 3 with antiphospholipid antibodies, in 1 in whom there was underlying HIV disease, 2 with viral hepatitis, 2 with rheumatoid arthritis (RA), 2 with cryofibrinogenemia, 1 with hypergammaglobulinemia, 1 with iritis, and 1 with Crohn's disease. In the other 21 patients, the clinical presentations prompted further studies in 12, which showed a positive antinuclear antibody (ANA) in 10. A diagnosis of idiopathic perniosis (IP) was rendered in all 21 of these patients including those in whom a positive ANA was discovered, based on the absence of any other serological markers, signs, or symptoms indicative of a specific systemic disease complex; many had Raynaud's phenomenon, small joint arthralgias, atopy, or a family history of either connective tissue disease or Raynaud's disease. The histopathology of IP comprised a superficial and deep angiocentric lymphocytic infiltrate with papillary dermal edema and lymphocytic exocytosis directed to retia and acrosyringia. A few cases showed a mild vacuolopathic or lichenoid interface dermatitis, adventitial dermal mucinosis, lymphocytic eccrine hidradenitis, vascular ectasia, and thrombosis confined to dermal papillae capillaries. The biopsies from patients with iritis, RA, and Crohn's disease showed a granulomatous vasculitis and a granuloma annulare-like tissue reaction. The biopsies from the patients with SLE, cryofibrinogenemia, primary antiphospholipid antibody syndrome, and hypergammaglobulinemia shared a similar histopathology comprising an interface dermatitis, superficial and deep angiocentric and eccrinotropic lymphocytic infiltrates, vascular ectasia, and dermal mucinosis with prominent involvement of the eccrine coil. Many cases did not show features of IP, namely papillary dermal edema, thrombosis of dermal papillary capillaries, and lymphocytic exocytosis into the retia and acrosyringia. There was frequent vascular fibrin deposition involving reticular dermal vessels. The latter two variables were statistically significant discriminators between IP and in perniotic lesions observed in the setting of underlying systemic disease. With respect to the latter, some cases occurred in the setting of cold exposure and were designated by us as "secondary perniosis" (SP), whereas others showed no specific association with cold exposure and were designated as perniotic mimics (PMs) based exclusively on the gross and microscopic morphology of the lesions.
10063761 Lumbar intraspinal synovial cysts of different etiologies: diagnosis by CT and MR imaging. 1998 Dec Intraspinal synovial cysts arises from a facet joint and may cause radicular symptoms due to nerve root compression. In the present study, three surgically and histologically proved cases of synovial cyst of the lumbar spine with different etiology are described. The purpose of this report is to illustrate the imaging features of various etiologies of intraspinal synovial cysts allowing a correct preoperative diagnosis. Review of the literature enables us to say that to our knowledge, there is no reported article collecting the imaging findings of intraspinal synovial cysts with different etiologies. Only single cases with rheumatoid arthritic or traumatic origin have been reported to date. We believe that computed tomography and particularly magnetic resonance imaging are the methods of choice which provide the most valuable diagnostic information.
9079816 Differences in mutational patterns between rheumatoid factors in health and disease are re 1997 Mar The sequences of the heavy chain variable (V(H)) segment and dissociation constants (Kd) of 14 IgM rheumatoid factors (RF) derived from 11 different germline gene segments from five healthy immunized donors (HID) are described. We extend a previous analysis of two clones from one donor using only the germline segment DP-10. In the present study, the mutation patterns of these new RF and the two earlier reported HID RF clones are analyzed in relation to V(H) family, germ-line origin, and Kd. The panel of HID RF is further compared with 33 previously described IgM RF from patients with rheumatoid arthritis (RA). There is a high rate of mutation in the panel of HID RF (mean of ten mutations/V(H)). RF originating in RA patients have a comparable mutation rate (mean of 11 mutations/V(H)), suggesting that hypermutation of IgM RF is not disease related. The HID RF have, however, a significantly lower affinity for IgG than the RA RF. We found that the structural basis of the differences between HID and RA RF is related to V(H) family usage. RF of the V(H)1 family use very similar germ-line genes in HID and RA patients. HID RF of the V(H)1 family have, however, a low ratio of replacement-to-silent (R:S) mutations of only 0.41 in the heavy chain complementarity region (CDR(H))1 and 2. This is statistically significantly lower than the corresponding ratio of 3.14 in the V(H)1 RA RF. In contrast, RF of the V(H)3 family from HID and RA patients have very similar R:S ratios of 1.75 and 1.71 in CDR(H)1 and 2, respectively. The V(H)3 RA RF are, however, predominantly encoded by genes not encoding any HID RF. Thus, both repertoire differences and hypermutation resulting in significantly lower R:S ratios can be observed in RF from HID compared with RA RF.
11477478 IL-1B and IL-1Ra gene polymorphisms and disease severity in rheumatoid arthritis: interact 2001 Jun The balance between interleukin-1 (IL-1) and its competitive antagonist IL-1 receptor antagonist (IL-1Ra) may contribute to the pathogenesis of rheumatoid arthritis (RA). We analysed the frequency of different alleles in the IL-1B gene (at -511 and at +3954) as well as in the IL-1Ra gene (at +2018) in an association study involving 297 RA patients and 112 healthy controls from the same geographic area. We tested associations with RA susceptibility or severity, and with circulating levels of IL-1Ra and IL-1beta. Carriage of the rare IL-1B (+3954) allele 2 was increased in destructive arthritis (DRA) as compared to non-destructive arthritis (NDRA) (OR 1.7, 95% CI 1.1-2.8, 49.0% vs 35.9%) and controls (OR 1.7, 95% CI 1.1-2.8, 35.8%). Patients carrying this allele had a more destructive (Larsen wrist radiological index: mean +/- s.e.m., 2.1 +/- 0.2 vs 1.6 +/- 0.1, P = 0.005; Steinbrocker functional index: 2.4 +/- 0.1 vs 1.9 +/- 0.1, P = 0.002) and active disease (Ritchie articular index: 8.1 +/- 0.8 vs 5.3 +/- 0.6, P = 0.002; erythrocyte sedimentation rate (ESR): 36.6 +/- 2.9 mm/h vs 25.3 +/- 1.8 mm/h, P = 0.002). This contribution was independent from that of HLA DR4/DR1 to severity. IL-1Ra plasma levels adjusted to ESR values were significantly lower in IL-1B2 (+3954) positive than negative RA patients (1.0 +/- 0.1 vs 1.2 +/- 0.1 ng/ml, P = 0.01). This IL-1B (+3954) gene polymorphism may be an important marker for the severity of joint destruction in RA and is associated with an imbalance in IL-1Ra production. As this genetic association was independent and additive to the risk of HLA DR4/DR1 status, it could be a useful addition to HLA-DR4/1 as a genetic prognostic marker early in the course of the disease.
9375540 Measurement of synovial tumor necrosis factor-alpha in diagnosing emergency patients with 1997 Nov Because of the high morbidity and mortality in patients with bacterial arthritis, rapidly and correctly diagnosing this critical condition is a challenge to emergency clinicians. Synovial fluid samples were obtained from 75 patients with arthritis disorders who presented to an emergency service, and levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were measured. Twenty patients with culture-proven bacterial arthritis had higher levels of synovial TNF-alpha than patients with osteoarthritis or with inflammatory arthritis, including gouty arthritis, rheumatoid arthritis, reactive arthritis, and lupus arthritis. There was a good sensitivity for synovial TNF-alpha level in diagnosing patients with bacterial arthritis. Nearly 100% of patients with bacterial arthritis had elevated synovial TNF-alpha levels. However, synovial IL-1 beta and IL-6 levels failed to discriminate bacterial arthritis from other inflammatory arthritis. Measurement of synovial TNF-alpha level may be useful as a diagnostic aid in emergency patients with bacterial arthritis disorders.
11406528 Haemopoietic stem cell transplantation in the treatment of severe autoimmune diseases 2000 2001 Jul An international meeting took place in Basel, Switzerland from 5 to 7 October 2000 involving 180 participants from 30 countries, with the aim of assessing the existing data on autologous haemopoietic stem cell transplantation (HSCT) in the treatment of severe autoimmune disease, and to decide on future trial planning. Data on 390 patients were presented: 260 from the EBMT/EULAR Basel European/Asian database, 87 from North America (55 from the IBMTR), 39 from Australia, and 4 others. The major disease categories and number of patients receiving transplant were: multiple sclerosis (MS) 127, systemic sclerosis (SSc) 72, rheumatoid arthritis (RA) 70, juvenile idiopathic arthritis (JIA) 36, systemic lupus erythematosus (SLE) 34, dermatomyositis/polymyositis (DM/PM) 5, idiopathic thrombocytopenic purpura (ITP) 7. Single or several cases of other autoimmune diseases were reported. Clinically significant responses were seen in two thirds of all the cases and in all disease categories, with a more accentuated trend towards relapse in JIA and RA. Treatment was associated with a significant morbidity and mortality. In the EULAR/EBMT database (71 centres in 22 countries), a mobilisation associated mortality of 1.5% and an overall procedure related mortality (actuarially adjusted at 12 months) of 9% (confidence interval 6 to 12%) were found, with significant variation between diseases. The North American data showed similar results. Higher mortalities were seen in SSc and systemic JIA, with only one death reported in RA. After presentation of the data and workshop discussion a consensus was reached on several aspects: prospective randomised phase III trials are now appropriate in SSc, MS, and RA. A protocol is ready for SSc (ASTIS Trial), concepts are clear for MS and RA. Further phase I and II data are required in SLE, JIA, and vasculitis. The need for continuing collection of all cases after mobilisation by the standardised EBMT and IBMTR data forms was emphasised.
11718502 Use of point-of-service health status assessments by community pharmacists to identify and 2001 Aug STUDY OBJECTIVE: To determine whether community pharmacists can use point-of-service health status assessments to identify and resolve drug-related problems (DRPs) in ambulatory patients with selected musculoskeletal (MSK) disorders. DESIGN: Twelve-month, prospective, multicenter demonstration project. SETTING: Twelve independent community pharmacies in eastern Iowa. PATIENTS: Ambulatory patients with self-reported diagnosis of osteoarthritis, rheumatoid arthritis, or low back pain. MEASUREMENTS: During quarterly pharmacy visits for 1 year, patients used touch-screen computers to report their health status. Patients answered questions on the Short Form-36 (SF-36) general health survey, as well as questions assessing limitations associated with their MSK condition. Pharmacists used this data in interviewing patients to assess for DRPs. MAIN RESULTS: The study enrolled 461 patients, of whom 388 returned for the 12-month visit. During this 1-year period, community pharmacists identified 926 cumulative DRPs. Patients with no DRPs had significantly higher physical component summary scores on the SF-36 (p<0.05) than patients with more than one DRP at baseline (36.2 vs 31.6), 6 months (39.2 vs 33.3), and 12 months (40.1 vs 35.4). At 12 months, actions performed by pharmacists led to resolution or improvement of 70.7% of DRPs. CONCLUSION: Drug-related problems are numerous in community-dwelling patients with MSK disorders and correspond to decreased physical health status. Community pharmacists can use patient-reported measures of health status to identify DRPs and initiate processes to resolve them.
10318942 Defining therapeutic targets by using adenovirus: blocking NF-kappaB inhibits both inflamm 1999 May 11 The role of the transcription factor NF-kappaB in the pathogenesis of rheumatoid arthritis has long been a subject of controversy. We used an adenoviral technique of blocking NF-kappaB through overexpression of the inhibitory subunit IkappaBalpha, which has the advantage that it can be used in the diseased tissue itself, with >90% of the synovial macrophages, fibroblasts, and T cells infected. We found that the spontaneous production of tumor necrosis factor alpha and other pro-inflammatory cytokines is NF-kappaB-dependent in rheumatoid synovial tissue, in contrast to the main anti-inflammatory mediators, like IL-10 and -11, and the IL-1 receptor antagonist. Of even more interest, IkappaBalpha overexpression inhibited the production of matrix metalloproteinases 1 and 3 while not affecting their tissue inhibitor. Blocking NF-kappaB in the rheumatoid joint thus has a very beneficial profile, reducing both the inflammatory response and the tissue destruction. The adenoviral technique described here has widespread applicability, allowing rapid testing of the effects of blocking a potential therapeutic target in either cultures of normal cells or in the diseased tissue itself.
9870876 Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist 1998 Dec OBJECTIVE: To evaluate the efficacy and safety of interleukin-1 receptor antagonist (IL-1Ra) in patients with rheumatoid arthritis (RA). METHODS: Patients with active and severe RA (disease duration <8 years) were recruited into a 24-week, double-blind, randomized, placebo-controlled, multicenter study. Doses of nonsteroidal antiinflammatory drugs and/or oral corticosteroids (< or =10 mg prednisolone daily) remained constant throughout the study. Any disease-modifying antirheumatic drugs that were being administered were discontinued at least 6 weeks prior to enrollment. Patients were randomized to 1 of 4 treatment groups: placebo or a single, self-administered subcutaneous injection of IL-1Ra at a daily dose of 30 mg, 75 mg, or 150 mg. RESULTS: A total of 472 patients were recruited. At enrollment, the mean age, sex ratio, disease duration, and percentage of patients with rheumatoid factor and erosions were similar in the 4 treatment groups. The clinical parameters of disease activity were similar in each treatment group and were consistent with active and severe RA. At 24 weeks, of the patients who received 150 mg/day IL-1Ra, 43% met the American College of Rheumatology criteria for response (the primary efficacy measure), 44% met the Paulus criteria, and statistically significant improvements were seen in the number of swollen joints, number of tender joints, investigator's assessment of disease activity, patient's assessment of disease activity, pain score on a visual analog scale, duration of morning stiffness, Health Assessment Questionnaire score, C-reactive protein level, and erythrocyte sedimentation rate. In addition, the rate of radiologic progression in the patients receiving IL-1Ra was significantly less than in the placebo group at 24 weeks, as evidenced by the Larsen score and the erosive joint count. IL-1Ra was well tolerated and no serious adverse events were observed. An injection-site reaction was the most frequently observed adverse event, and this resulted in a 5% rate of withdrawal from the study among those receiving IL-1Ra at 150 mg/day. CONCLUSION: This study confirmed both the efficacy and the safety of IL-1Ra in a large cohort of patients with active and severe RA. IL-1Ra is the first biologic agent to demonstrate a beneficial effect on the rate of joint erosion.
10754341 CD30+ T cells in rheumatoid synovitis: mechanisms of recruitment and functional role. 2000 Apr 15 High serum levels of soluble CD30 (sCD30) have been reported to better predict the response to second line therapy in rheumatoid arthritis (RA). It is believed that sCD30 is released by CD30+ T cells present in the RA synovium. However, both the mechanism of recruitment to the joint and the functional role of this T cell subset in the pathogenesis of the disease remain unknown. This study confirmed higher levels of sCD30 in the serum and synovial fluid (SF) of RA patients compared with normal controls. However, analysis of mRNA and cell surface CD30 expression showed that CD30+ T cells are detectable in the SF, but not in the synovial membrane. In contrast, T cells expressing the CD30 transcript, but not the surface molecule, were found in the peripheral blood of both RA and normal controls. CD30 surface expression was up-regulated by adhesion and migration through endothelium in vitro and in a delayed-type hypersensitivity model in vivo. Although the great majority of fresh or cloned CD30+ T cells from SF produced both IFN-gamma and IL-4, CD30 expression strictly correlated with IL-4 synthesis in synovial T cell clones. In addition, CD30+ T cell clones also produced high amounts of the anti-inflammatory cytokine IL-10. On this basis, we would like to propose that synovial CD30+ cells may play a role in the control of the inflammatory response. Serum sCD30 may reflect such cell activity and, therefore, explain the previously demonstrated correlation between high sCD30 serum levels and positive response to therapy.
9743216 Autoantibody patterns in synovial fluids from patients with rheumatoid arthritis or other 1998 Sep Patients with rheumatoid arthritis (RA) produce a variety of autoantibodies, not only demonstrable in the circulation, but also locally in the inflamed joint. We investigated the local production of several autoantibodies in the synovial fluid (SF) of 24 patients with RA and of 26 patients with other arthritic lesions. RA patients had higher titres of immunoglobulin M (IgM) and immunoglobulin G (IgG) rheumatoid factors (RFs) and of collagen type II antibodies in SF, whereas there were no demonstrable differences between groups with regard to antibodies against double-stranded (ds) DNA, C1q or the hapten 2,4,6-trinitrobenzene sulfonic acid (TNP). No differences were observed for total synovial levels of IgM or IgG. There was no autoantibody pattern that was typical of RA patients, except for the local presence of RF, primarily in seropositive RA patients. Our findings therefore support the notion that RF and collagen type II antibodies are induced by immunogenic material present in the local inflamed environment. In the accompanying paper we studied various synovial fluid cytokines in the same patient groups. Here we correlated the level of these cytokines with autoantibody titres in SF, but no specific cytokine associated with the production of RF was found. Hence, we conclude that several different inflammatory mediators might contribute to the chronic inflammation and autoantibody production in the joint of RA patients. An inverse correlation was established between concentrations of tumour necrosis factor-alpha (TNF-alpha) and levels of total IgG.
9858437 Chronic arthritis and carpo:metacarpal ratio in Japanese patients with adult Still's disea 1998 Dec OBJECTIVE: To characterize Japanese patients having adult Still's disease (ASD) with chronic arthritis (> 6 months) and to examine the association of chronic arthritis with carpo:metacarpal ratio (CMC ratio), an index of radiographic progression in rheumatoid arthritis (RA). METHODS: Twenty-seven patients with ASD (16 women and 11 men, mean age at disease onset 27.7 years) were classified into 2 groups: patients with (chronic articular ASD, 16 patients, 59%) or without (systemic ASD, 11 patients, 41%) chronic arthritis. Clinical and laboratory findings were compared between both groups. CMC ratio was calculated on serial hand radiographs in patients with chronic articular ASD. RESULTS: In our series, serositis was rarely observed in chronic articular ASD. Peripheral arthritis (including transient arthritis), such as metacarpophalangeal, proximal interphalangeal, or ankle joint, was more frequently observed in chronic articular ASD than in systemic ASD (p < 0.05). Wrist arthritis was frequently observed also in systemic ASD; however, joint space narrowing of carpometacarpal or intercarpal joints was recognized only in chronic articular ASD (44%). CMC ratio at the last observation in 14 patients with chronic articular ASD was significantly decreased (0.526 +/- 0.039) compared to that at disease onset (0.553 +/- 0.034) (p < 0.05), while no decrease was observed in 4 with systemic ASD (0.565 +/- 0.062 at disease onset, 0.563 +/- 0.043 at the last observation). CONCLUSION: It is suggested that chronic articular ASD has certain characteristics. CMC ratio may be a quantitative index for assessment of radiographic changes of carpal joints, not only in RA but also in chronic articular ASD.
10441172 Multicenter evaluation study on a new HEp2 ANA screening enzyme immune assay. 1999 Aug The COBAS Core HEp2 ANA enzyme immune assay (EIA) was evaluated in a precision and a clinical sample study in comparison to indirect immunofluorescence assay (IFA) on HEp2-cells. In the precision study the COBAS Core EIA yielded intraassay coefficient variations (CVs) mostly below 9%, and interassay CVs between 4.7% and 10.4%. When comparing the COBAS Core EIA to IFA, the results corresponded well in healthy subjects, systemic lupus erythematosus, mixed connective tissue disease and rheumatoid arthritis. In the case of Sjögren's syndrome and scleroderma patients the COBAS Core EIA yielded a lower rate of positive results compared to IFA. This discrepancy may be explained by the lack of detection of autoantibodies to nuclear antigens that can be identified only by IFA due to their compartmentalization and higher localized antigen density in HEp2 cells. The discrepancies in the group of dermato/polymyositis patients are due to the fact that the EIA contains mainly nuclear antigens and was able to detect only antibodies against the cytoplasmic Jo1 antigen that was added to the HEp2 nuclear extract. Routine sera were also evaluated; good agreement was found in sera from patients attending tertiary reference centres for autoimmune diseases but a higher number of discrepancies was reported in sera from unselected populations.
11238664 Functional IL-2 receptor beta (CD122) and gamma (CD132) chains are expressed by fibroblast 2001 Mar 15 The expression of the IL-2R alpha-, beta-, and gamma-chains, CD25, CD122, and CD132, respectively, was investigated on fibroblast-like synoviocytes (FLS) and dermal fibroblasts (DF). Both protein and mRNA for CD122 and CD132 were observed but there was no evidence of CD25 expression. Quantification of the Ag binding sites for CD122 showed that FLS expressed 4 times more receptor molecules than DF. The functional capability of these receptors was confirmed by the production of monocyte chemoattractant protein-1 (MCP-1) in direct response to stimulation by IL-2, which could be inhibited by neutralizing anti-CD122 mAb. Both rheumatoid arthritis (RA) and osteoarthritis (OA) FLS and DF spontaneously produced MCP-1 in culture over a similar range of concentrations. However, RA and OA FLS produced significantly greater levels of MCP-1 following stimulation by IL-2 and IL-1 beta; RA FLS produced significantly more MCP-1 than OA FLS. Addition of exogenous IL-2 caused a slight, but significant, decrease in MCP-1 production by DF. The addition of neutralizing anti-CD122 mAb to FLS cultures partially, but significantly, reduced the IL-2-induced MCP-1 secretion, but did not effect either the spontaneous or IL-1 beta-induced secretion of MCP-1. Increased tyrosine phosphorylation was observed in FLS lysates following 30-min incubation with IL-2. In conclusion, in the inflamed synovium, as activated T cells migrate through the sublining and lining layer, T cell-derived IL-2 may activate FLS to secrete MCP-1, thus recruiting macrophages into the rheumatoid synovium and perpetuating inflammation.
9324017 Transcriptional regulation of the HOX4C gene by basic fibroblast growth factor on rheumato 1997 Sep OBJECTIVE: To examine the expression of genes of the HOX D cluster in the synovial tissue of patients with rheumatoid arthritis (RA), and to determine whether basic fibroblast growth factor (bFGF) influences the expression and transcriptional regulation of the gene. METHODS: The expression of genes of the HOX D cluster, including HOX4C, HOX4D, HOX4H, and HOX4I, was determined in the synovium of 4 patients with RA and 4 with osteoarthritis (OA) by in situ reverse transcription (RT) and RT-polymerase chain reaction (RT-PCR). The induction of HOX4C messenger RNA (mRNA) by bFGF was determined by RT-PCR. The binding activity of a transcriptional regulator of the HOX4C gene, C2, was analyzed by the mobility shift assay. NIH-3T3 cells transfected with a construct containing C2 binding sequence were incubated with bFGF, and the activity of the reporter was measured by luciferase assay. RESULTS: Using an in situ RT assay, specific expression of HOX4C mRNA was detected in 3 of 4 RA synovial samples, whereas none of the OA synovia expressed HOX4C. HOX4D, HOX4H, and HOX4I genes were expressed in all synovial samples from RA and OA patients. The presence of HOX4C mRNA was also confirmed by RT-PCR and Southern blotting. Treatment with bFGF increased the expression of HOX4C mRNA in RA fibroblasts. The mobility shift assay and luciferase assay showed that bFGF enhanced C2 binding activity and significantly increased the transcriptional activity on RA fibroblasts. CONCLUSION: Our findings suggest that HOX4C is involved in synovial hyperplasia, and that the transcriptional regulation of HOX4C genes by bFGF may play a crucial role in the pathogenesis of RA.