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ID PMID Title PublicationDate abstract
8380369 Clonality of T lymphocytes expanded with IL-2 from rheumatoid arthritis peripheral blood, 1993 Jan The association of rheumatoid arthritis (RA) with particular MHC class II genes suggests that autoantigen-specific T cell clones present in joints could be central to the pathogenesis of the disease. Previous investigations on the clonal diversity of T cells infiltrating the rheumatoid synovial membrane have yielded conflicting results. With the use of Southern blot analysis, we investigated the clonality of rheumatoid T cell lines expanded from peripheral blood, synovial fluid and synovial tissue. From peripheral blood lymphocyte (PBL) of RA patients and healthy normal controls, we also checked the consequences of two different culture conditions on the clonality of these cell lines. From control PBL, we found that in vitro non-specific expansion of non-clonal T cell populations does not create artefactual clonal selection. However, growing T cells in vitro with IL-2 seems to be able to lead to preferential expansion of cells bearing IL-2 receptor (IL-2R). We identified such in vivo activated IL-2-sensitive T cell clones frequently in RA synovial tissue (8/13) and more rarely in synovial fluid and peripheral blood (3/12). One patient presents the same T cell receptor gene rearrangements in synovial membrane of two affected joints. In RA synovial tissue, the frequency of these IL-2-responsive T cells is most prevalent among actively inflamed membranes removed early in the disease process. The role and the relevance to the disease of these IL-2-responsive T cells remain to be elucidated.
8215619 Physical activity as a determinant of bone conservation in the radial diaphysis in rheumat 1993 Aug OBJECTIVES: To determine if increasing physical activity is protective of diaphysial (cortical) bone mass METHODS: Fifteen patients attending two rheumatology clinics who had developed seropositive or classical rheumatoid arthritis up to 26 months previously were studied prospectively for two to three years. Rates of loss (or gain) in bone mass in the radial diaphysis and the trabecular bone of the distal radius were measured by quantitative computed tomography, and in the spine by dual photon absorptiometry. Physical activity was assessed by the Framingham physical activity index. Disease activity was followed at three-monthly clinic visits at which the haemoglobin, erythrocyte sedimentation rate, and platelet count were measured. The urinary hydroxyproline to creatinine ratio and plasma osteocalcin were measured at the beginning and end of the observation period. RESULTS: Eleven patients required treatment with disease modifying drugs but none was given corticosteroids. Those whose physical activity did not improve lost radial diaphysial bone at about 4% annually. There was, however, a statistically significant inverse relation, accounting for 48.5% of the variance, between bone loss at this site and improvement in physical activity as assessed by the Framingham index. The other two sites showed much weaker associations. Adjusting for indices of disease activity hardly affected the first relation. Three biochemical indices related to bone turnover showed weak tendencies to decrease with increasing physical activity. CONCLUSIONS: Peripheral cortical bone, distant from inflamed joints, is conserved more successfully in patients who achieve higher levels of physical rehabilitation. This may have implications for avoiding long bone fractures later in the disease.
7889971 Mycoplasma genitalium in the joints of two patients with arthritis. 1994 Dec Mycoplasma genitalium was sought in synovial fluids from 13 patients, of whom five had Reiter's syndrome, four had rheumatoid arthritis, and one each had systemic lupus erythematosus, psoriatic arthritis, rheumatic fever and undefined arthritis. The mycoplasma was detected by a PCR assay in the knee joint of a 25-year-old man with Reiter's syndrome, from whom urethral ureaplasmas were isolated and whose synovial fluid mononuclear cells responded to ureaplasmal antigens in a proliferation assay. Mycoplasma genitalium was also detected in the knee joint during an exacerbation of arthritis in a 58-year-old man who had had seronegative juvenile polyarthritis that had evolved to seronegative rheumatoid arthritis.
1411299 TCR gamma/delta+ cell subsets in the synovial membranes of patients with rheumatoid arthri 1992 Oct Using a peroxidase/anti-peroxidase immunohistochemical staining method, we examined sections of inflammatory synovial membranes from 13 patients with juvenile rheumatoid arthritis (JRA) and 11 with rheumatoid arthritis (RA). The relative numbers of TCR gamma/delta+ cells and the proportions of V delta 1+ and V delta 2+ subsets were recorded in the areas of the membranes most heavily infiltrated by CD3+ cells. In the JRA group, the majority (8/13) of the membranes had TCR gamma/delta+ cells which contributed between 5 and less than 10% of the total number of CD3+ cells. In the RA synovial membranes examined, 5/11 samples had between 5 and 10% TCR gamma/delta+ cells, but in another 5 TCR gamma/delta+ cells contributed to between 10 and 20% of CD3+ cells. No significant difference was noted between the two patient groups. However, the range of values found in the RA membranes appeared to be slightly higher in comparison to previously reported values for RA synovial fluid, peripheral blood and eluted synovial membrane T cells. Analysis of the relative proportions of the V delta 1+ and V delta 2+ subsets revealed a significant dominance of V delta 1+ cells in RA membranes and approximately equal numbers of the two populations in the JRA patients. As the majority of peripheral blood TCR gamma/delta+ cells use the V delta 2 segment this suggests a preferential homing or expansion of the V delta 1+ cells in both RA and JRA synovium. The overall distribution pattern of the TCR gamma/delta+ and V delta 1+ and V delta 2+ cells was also recorded. These cells mostly accumulated in the lymphoid-like tissues and in the perivascular area in the tissues of both RA and JRA patients. Occasionally, augmented numbers of these cells were found in the subsynovial layer or in the loose connective tissue. In the majority of cases, only a few TCR gamma/delta+ cells were located in the synovial layer. The function and the possible pathogenetic importance of these TCR gamma/delta+ cells have not so far been determined.
8240428 The effect of rheumatoid arthritis and steroid therapy on bone density in postmenopausal w 1993 Nov OBJECTIVE: To assess bone mineral density (BMD) in postmenopausal women with rheumatoid arthritis (RA) and the relative effects of disease activity, disability, and past and current use of corticosteroids. METHODS: One hundred ninety-five postmenopausal patients with RA were compared with 597 post-menopausal control subjects. Bone density was measured at the lumbar spine and the proximal femur using dual x-ray absorptiometry. Patients were divided into 3 groups according to corticosteroid use, i.e., never users (61%), current users (21%), and ex-users (18%). RESULTS: Compared with controls, the never users had no difference in BMD at the lumbar spine, but a 6.9% reduction at the femur (95% confidence interval [95% CI] 3.4-10.3%). In current users (mean daily prednisolone dosage 6.9 mg), BMD was reduced by 6.5% at the spine (95% CI 0-13.0%) and by 7.4% at the hip (95% CI 1.2-13.6%) compared with never users, after adjustment for age, weight, duration of menopause, and functional disability. Mean BMD was similar in the ex-user and never user groups. Results were confirmed in 54 patients who had whole-body BMD measurements. There were inverse correlations between BMD and Health Assessment Questionnaire scores (femoral BMD r = -0.23, P < 0.01; whole-body BMD r = -0.40, P < 0.01) and between BMD and cumulative steroid dose (femoral BMD r = -0.32, P < 0.01; whole-body BMD r = -0.72, P < 0.01). CONCLUSION: Osteoporosis in postmenopausal women with RA is more evident at the hip than the spine, and the most important determinants of bone loss are disability and cumulative corticosteroid dose. Low-dose steroids cannot be used with complacency, but recovery after discontinuation of use may be possible.
1457588 Iron stores and serum transferrin receptor levels during recombinant human erythropoietin 1992 Dec Ten rheumatoid arthritis (RA) patients with anemia of chronic disorders (ACD) were treated with recombinant human erythropoietin (r-Hu-Epo) using a dose of 250 U/kg s.c. 3 times a week for 6 weeks, in order to evaluate its effects on the anemia, iron stores, and serum-soluble transferrin receptor (sTfR) levels. All patients showed a rise in hemoglobin (Hb). Median Hb increased from 5.9 (5.5-7.0) at baseline to 6.7 (5.8-7.8) at 3 weeks and to 7.2 (5.9-8.5) mmol/l at 6 weeks during treatment. Ferritin levels decreased significantly during the 6 weeks, and five patients were iron deficient after 6 weeks of treatment. TfR levels increased significantly at 3 and 6 weeks during treatment. These preliminary findings may indicate that r-Hu-Epo is effective in improving ACD in RA. The sTfR rise may be explained by an increase in erythroid precursor cell mass or increased TfR expression and a decrease in tissue iron stores, although direct effects of Epo on TfR regulation cannot be excluded. Large double-blind studies with r-Hu-Epo in patients with RA and ACD are warranted.
8264896 Fusion with occipital bone for atlantoaxial instability: technical note. 1993 Nov A technique is described of using autologous occipital bone for posterior atlantoaxial fusions. The advantages include the ease of harvest, the lack of postoperative discomfort, and the suitability of occipital bone for the fusion.
8591650 Innovative treatment approaches for rheumatoid arthritis. Cyclosporin, leflunomide and nit 1995 Nov Cyclosporin A (CSA) Cyclosporin inhibits IL-2 release and T-cell activation and, secondarily, affects B-cell function. It also inhibits bone resorption, at least in vitro. This drug's bio-availability averages 25-35% but is highly variable. Food and grapefruit juice enhance bio-availability and newer formulations may make its absorption more reliable. It is highly concentrated in fatty tissues and red blood cells but does not cross the blood-brain barrier. CSA is metabolized to numerous metabolites by the liver and its elimination half-life is 6-12 hours in the absence of severe liver disease. Biliary excretion accounts for 94% of CSAs elimination. Because it is highly metabolized, its metabolism can be inhibited by other drugs (e.g. ketoconazole and erythromycin) or its metabolism can be induced (e.g. anticonvulsants). Cyclosporin is more effective than placebo for the treatment of rheumatoid arthritis and as effective as other antirheumatics. There is potential for the use of CSAs in DMARD combinations. The principal toxicities of cyclosporin are gastro-intestinal and renal, with the latter being of more concern. Leflunomide (LF). Leflunomide may be a pyrimidine synthesis inhibitor, although tyrosine kinase inhibitor may also be part of its mechanism of action. Its active metabolite is excreted renally to a large degree, with a prolonged elimination half-life of about 11 days. Since LF is activated by liver metabolism, renal failure may have less effect on kinetics than severe liver disease. Early data on efficacy indicate efficacy at 10-25 mg/day, although more well-controlled data is necessary. Toxicity relates to the skin, liver and GI tract, although some degree of weight loss was also found. Nitrogen mustard (NM). Nitrogen mustard is an alkylating agent whose pharmacokinetics are poorly understood. Small, open studies in RA indicate that NM has a potential for relatively rapid response (1-2 weeks) but, clearly, much work remains to be done. As an alkylating agent, GI and hematological toxicities are of greatest concern.
8508289 Life-threatening haemorrhage in a patient with rheumatoid arthritis and a lupus anticoagul 1993 Jun A case history of a patient with RA and a lupus anticoagulant coexisting with an acquired inhibitor to factor VIII is described. The factor VIII inhibitor was heralded by life-threatening haemorrhage which followed an invasive procedure.
1424551 Remaining teeth, oral dryness and dental health habits in middle-aged Norwegian rheumatoid 1992 Oct The aim of the study was to assess the effect of rheumatoid arthritis (RA) upon dental health. A questionnaire was mailed to all seropositive rheumatoid arthritis (RA) patients aged 44-56 yr in the files of the two main departments of rheumatology in South Eastern Norway. Data were obtained from 125 patients, constituting 91% of the target group. The number of remaining teeth in these patients was not related to disease duration or physical dysfunction, whereas a relationship to prolonged use of medication for pain relief was indicated. Factors known to affect tooth loss in the general population, such as smoking habits, dental attendance, interdental cleaning habits, previous dental disease, and place of residence were found to be important in RA patients as well. The RA patients from Oslo had a mean number of 25 remaining teeth, which is the same as reported for the general Oslo population at this age. Oral dryness was reported by more than 50% of the RA patients, but was not related to the number of teeth. The conclusion is that serious and long lasting rheumatoid arthritis had little influence on the number of remaining teeth in this middle-aged group of Norwegians.
7869306 Combination therapy of cyclosporine with methotrexate and gold in rheumatoid arthritis (2 1994 Nov OBJECTIVE: To evaluate the efficacy and toxicity of cyclosporine A (CyA) in combination with gold and methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: Twenty patients with RA with partial response to oral MTX and 20 patients with partial response to im gold had CyA added to their regimen for 6 months, withdrawn over 2 months and the patients monitored for 4 months. RESULTS: There was a significant improvement in joint count, joint score, joint swelling, grip strength and joint pain in patients taking the combination with no significant increase in adverse reactions. CONCLUSION: CyA in combination with gold or MTX may, over a 6 month period, increase efficacy in patients with refractory RA without significant increase in toxicity.
8414489 [Ultrasonographic diagnosis in inflammatory-rheumatic changes of the shoulder joint]. 1993 Sep Inflammatory rheumatoid changes of the shoulder joint are often diagnosed rather late, so therapy is largely directed towards pain reduction and less towards maintenance of full joint function. When considering the mutilating type of chronic polyarthritis, it becomes evident how important the role of the shoulder joint is in the patients performance of basic everyday activities. In this paper the important structures of the shoulder joint that can be visualized by ultrasound are described as to their rheumatological significance, and pathological findings are discussed along with the appropriate therapy.
8320081 Suppression of murine collagen-induced arthritis by treatment with a novel thiazole deriva 1993 Jan The antiarthritic activity of a novel thiazole derivative, SM-8849, was compared with that of indomethacin and D-penicillamine, in mice with collagen-induced arthritis. SM-8849 reduced the incidence and severity of disease in collagen-immunized mice, as assessed by clinical observation. This efficacy was also confirmed by radiographic and histologic studies. Indomethacin produced an apparent reduction of the clinical score, but had only a marginal effect on bone destruction. D-penicillamine did not produce any improvement. Unlike indomethacin and D-penicillamine, SM-8849 reduced the serum levels of anti-type II collagen antibodies. Flow cytometric analysis of spleen cells from arthritic mice revealed an increase in T cells expressing activation antigens (class II antigens) in comparison with normal mice. Treatment with SM-8849, but not indomethacin or D-penicillamine, prevented the increase in Ia-bearing T cells. The results suggest that an effect of SM-8849 on immunocompetent cells may be responsible for the antiarthritic activity of the compound, and this would distinguish its action from that of traditional antirheumatic drugs.
8484093 T-cell receptor V beta chain expression in patients with juvenile rheumatoid arthritis. 1993 The V beta chain repertoire in peripheral blood T-cell was analyzed in 23 patients with juvenile rheumatoid arthritis (JRA). Of these, 15 patients had active disease as defined by tender and swollen joints. The ESR was elevated in all but three patients, C-reactive protein (CRP) was elevated in eight. Three patients were investigated during active and inactive phases of the disease. In the active phase of the disease T-cell composition was characterized by an increased number of CD4+ helper cells due to a marked increase in the CD4+CD45RA+ subgroup (34.0 +/- 10.9%, P < 0.001) and a decrease in CD8+CD29+ T-cells (10.3 +/- 5.6%, P < 0.05) compared to controls (15.4 +/- 10.0% and 17.8 +/- 12.3%, respectively). Using the monoclonal antibodies available to determine T-cell receptor (TCR) expression, patients with active disease demonstrated a significant predominance of T-cells bearing TCRs of the V beta 5 family as determined by flow cytometry (7.6 +/- 6.7 vs 3.4 +/- 1.3 in controls, P = 0.01). In active polyarthritis, up to 24% of peripheral blood T-cells expressed TCRs of the same family. In the majority of JRA patients and especially in non-active disease, no preferential TCRs were found compared to controls. However, even defining only a part of TCRs by immunofluorescence, in certain patients a preferential or dominant expression of a single V beta gene family in the T-cells was found, supporting the concept of an involvement of T-cells in the autoimmune pathogenesis of JRA.
8711535 [Clinical characteristics and genetic background of secondary amyloidosis associated with 1996 Feb In order to examine the clinical characteristics and genetic background of secondary amyloidosis associated with rheumatoid arthritis, we analyzed clinical features and HLA typing of 85 patients in a multicenter study. Eighty-five patients with secondary amyloidosis associated RA were studied. The diagnosis of secondary amyloidosis were made on histological findings by biopsy or autopsy. The most common biopsy site was gastrointestinal tract (79.5%). Clinical symptom and the frequency at the time of diagnosis were; diarrhea (35 cases), abdominal pain (22 cases) and vomiting and nausea (16 cases). Abnormalities and the frequency in a laboratory test included proteinuria (49 cases), increased serum creatinine (32 cases), anemia (30 cases) and hematuria (15 cases). Twenty-eight patients were dead and 57 patients were alive at the time of the study. The average duration between diagnosis of amyloidosis and death was 19.4 +/- 18.5 (SD) months among the dead patients. The average duration after diagnosis of amyloidosis was 24.2 +/- 19.5 (SD) months in surviving patients. The causes of death were renal failure complicated with heart failure (6 patients), heart failure alone (3 patients) and renal failure alone (2 patients). Fifty-nine patients in the control group who were negative to amyloid deposition on biopsies at more than one site in the gastrointestinal tract, were clinically compared with patients in the amyloidosis group. No difference were noted in the age of RA occurrence and the stage between the two groups. As to the class, however, the number of patients with severe functional disorder (class 3 or severe) was larger in the amyloidosis group. There were no significant difference between the two groups in Lansbury's activity index. On hematology, biochemistry and urinalysis, the incidences of increased white blood cell count, anemia, increased platelet count, increased serum creatinine, hypoproteinemia, hypoalbuminemia, increased IgA, and increased urine and blood BMG were statistically significantly higher in the amyloidosis group than in the control group. HLA-A, -B, -C, and DR-locus antigens were compared in the 53 patients in the amyloidosis group and in the 59 subjects in the control group. There were no significant differences in frequency of HLA-A, and -B antigens between two groups. Frequency of CW7 antigen was significantly decreased in the amyloidosis group (13.2%) than in the control group (39.0%). Frequency of DR1 antigen was decreased in the amyloidosis group (3.8%) than in the control group (22.0%), although the difference was not significant. These findings suggest the possible involvement of genetic factors in the occurrence of amyloidosis. It is suggested that the occurrence of amyloidosis is suppressed by some genes which are linked with CW7 antigen.
8218839 A minor group of rheumatoid factors isolated from a patient with rheumatoid arthritis is d 1993 To better understand the structural basis for rheumatoid factor [RF] activity and the origin of autoantibodies in human autoimmune diseases, we isolated the RF producing B cells from the peripheral blood and from the synovial fluid of a patient suffering from rheumatoid arthritis [RA]. We previously demonstrated that a significant fraction of these RF were derived from three V kappa III genes known to encode most of the monoclonal RF light chain variable regions. To get more insight into the actual repertoire of RF-V kappa genes during RA, we analyzed the nucleotide sequences of RF light chain variable regions of other V kappa families. Using two sets of polymerase chain reactions in order to amplify the cDNA derived from RF producing cells from the same patient KRA, we isolated only three different rearranged V kappa-J kappa complexes: slkv5, slkv7 and bkv42, all derived from V kappa I germ-line genes not previously known to be associated with RF activity; this suggests that the repertoire of VL genes coding for RF during RA is more diverse than the one involved in the generation of paraprotein RF during monoclonal lymphoid proliferations, although there remains a possible bias in favor of the V kappa III family. Moreover, each of these genes is somatically mutated with a pattern suggesting a selective pressure of the antigen. Particularly interesting is the additional proline residue at the V kappa-J kappa junction of bkv42, an unorthodox feature that we found previously in more than 50% of RF V kappa III-J kappa gene complexes. Finally, the homogeneity of some non conservative mutations suggests the existence of a restricted set of pathogenic epitopes driving the production of RF during RA.
7689047 Autoantibodies to neutrophil cytoplasmic enzymes in Felty's syndrome. 1993 May In this study we determined the occurrence of anti-neutrophil cytoplasmic antibodies (ANCA) and the specificity of these antibodies (Ab) in the serum of patients with Felty's syndrome (FS) and in serum of patients with uncomplicated rheumatoid arthritis (RA). ANCA, detected by indirect immunofluorescence on ethanol-fixed neutrophils, was found in 77% of 30 patients with FS and in 36% of 50 RA patients. Ab against lactoferrin (LF) occurred more frequently in FS patients (50%) than in RA patients (4%), whereas reactivity against the other cytoplasmic antigens tested (proteinase-3, myeloperoxidase and elastase) did not differ significantly between these patient groups. The specific reactivity of FS sera with LF was established by demonstrating that the Ab reactivity resided in IgG, was located in the F(ab')2 fragments and could be inhibited from binding to the ELISA plate-bound LF by purified LF in the fluid phase. These results demonstrate that anti-LF Ab occur in FS and suggest that the detection of anti-LF Ab in patients with FS may be useful in the diagnosis of FS.
8229232 Comparison of methods for identifying early methotrexate-induced hepatotoxicity in patient 1993 Nov Hepatotoxicity may complicate therapy with methotrexate in patients with rheumatoid arthritis. Prevention of cirrhosis may depend upon early identification of liver damage, usually accomplished by serial biopsy. To determine the adequacy of noninvasive methods for identifying hepatotoxicity, 22 sets of data were obtained in patients undergoing therapy with methotrexate for rheumatoid arthritis. Comparisons were made between liver biopsy, hepatocellular enzymes and two noninvasive radioisotopic methods that have been shown to be abnormal in hepatocellular disease: the rate constant of excretion of the 14C-aminopyrine and the time from injection to peak hepatic activity of 99mTc-diisopropylimidodiacetic acid. The hepatocellular enzymes and the time-to-peak-activity of diisopropylimidodiacetic acid were not useful predictors of methotrexate-induced hepatotoxicity. The aminopyrine breath test was abnormal in approximately half the patients with hepatotoxicity but showed poor specificity. Noninvasive methods remain inferior to biopsy for the detection of mild to moderate methotrexate-induced hepatotoxicity in patients with rheumatoid arthritis.
7541651 IgG3 reactive rheumatoid factor in rheumatoid arthritis: etiologic and pathogenic consider 1994 Rheumatoid factor (RF) is a polyclonal autoantibody directed against the Fc portion of IgG. Although the role of RF in patients with rheumatoid arthritis (RA) is unclear, immune complexes that form between RF and IgG can activate the classical complement (C) pathway, leading to pathogenic outcomes involving inflammatory events and tissue damage. The specificity of serum RF and RF produced by rheumatoid synovial cells (RSC) is different. Serum RF has specificity for rabbit IgG and human IgG subclasses IgG1, 2, and 4, but binds poorly to IgG3. The affinity of serum RF for IgG Fc is low, having an association constant of 10(4)-10(5) M-1. RSC RF, however, has specificity for human IgG and high avidity for IgG3. Because of this greater specificity and avidity for IgG3, and because RSC RF may be pathogenically more important than serum RF, an important role for IgG3-reactive RF in RA may exist. Binding of RF to IgG may be dependent on the allotype and glycosylation of IgG. Infectious agents present in RA patients may directly or indirectly induce the production of certain RF. In this communication, we review and expand on several observations examining the role of IgG3-reactive RF in RA including: 1) binding differences between RF derived from RSC and serum; 2) glycosylation characteristics of IgG and its interaction with RF; 3) apparent allotype dependent binding of IgG3-reactive RF; and 4) possible relationship between infectious agents and the production of IgG3-reactive RF. Taken together, these observations suggest an important role for IgG3-reactive RF in better understanding the etiology and pathogenesis of RA.
1486749 Human parvovirus B19 and rheumatoid arthritis. 1992 Dec Human parvovirus B19 infections have been linked with the development of a short-lived symmetrical polyarthritis and, rarely, a more persistent arthritis. We prospectively looked for serological evidence of recent B19 infection in 25 early synovitis patients presenting within 12 weeks of symptom onset and compared them with 21 controls seen over the same time period. None of the control patients had evidence of recent B19 infection while 3 of the early synovitis patients had raised IgM anti-B19 antibody levels. Two had a transient arthritis and 1 developed persistent seropositive rheumatoid arthritis.