Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
2087396 [A study of MRI diagnosis for rheumatoid arthritis in the knee joint--imaging and patholog 1990 Nov 25 We performed MR (magnetic resonance) imaging of 25 knee joints in 20 patients with rheumatoid arthritis (RA) before synovectomy and the findings were compared with the pathological specimens. When based on the findings on T2-weighted images of the examined joints, the degree of joint involvement by RA could be divided into four stages: stage 1 in which only joint effusion was present; stage 2 in which synovial thickening, lower in signal intensity than joint effusion, was present; stage 3 in which cartilage destruction was present; stage 4 in which apparent bone destruction was present. There were eleven joints which appeared unremarkable on conventional X-ray films but three of them were at stage 2 and six at stage 3. In conclusion, MR imaging is of help in diagnosis of early involvement of the knee joints by RA.
2680236 Urine- and serum beta 2-microglobulin in patients with rheumatoid arthritis: a study of 10 1989 Sep Serum levels and 24-hour urinary excretion of beta 2-Microglobulin (beta 2-M) was investigated in a group of 101 patients with rheumatoid arthritis (RA), without any other signs of renal disease in past or present, and in a comparable control group. Elevated 24-hour urinary beta 2-M excretion, due to renal proximal tubules dysfunction, was observed in 19% of the patients and not in the control group. There was a significant correlation with clinical signs of extra-articular RA. It is postulated that the observed increase may be an early symptom of renal involvement in RA. Elevated serum beta 2 levels, corrected for glomerular filtration rate, were observed in 44% of the RA patients and only in 3% of the control group and correlated with clinical signs of a more severe RA, as well as with increased 24-hour urinary beta 2-M excretion.
2390124 Serologic and molecular characterization of a human monoclonal rheumatoid factor derived f 1990 Aug Molecular characterization of rheumatoid factors (RF) in rheumatoid arthritis (RA) has been hampered because of their polyclonality. To overcome this problem, we generated monoclonal RF-secreting hybridomas from rheumatoid synovial cells. Among the RF-secreting hybridomas, HAF10 secreted an IgM-RF that was monospecific for human IgG. It bound well to IgG1 and IgG2, but not to IgG3 and IgG4. Sequence analysis of its heavy and light chains showed that it contained a VH1 heavy chain and a V lambda light chain that did not belong to any known lambda light chain subgroup, and therefore, probably represented a new lambda subgroup. These results indicated that both the heavy and light chains of a monoclonal IgM-RF from rheumatoid synovial cells were quite different from the reported variable region sequences of several monoclonal RF derived mainly from patients with mixed cryoglobulinemia. Further studies of additional monoclonal RF from RA patients are warranted to define precisely their genetic basis and to further our understanding of the immunopathology of RA.
2977188 Immunogenetic and racial determinants of gold toxicity in rheumatoid arthritis. 1988 Feb Typing for antigens HLA-A,B,C and DR was performed on 165 rheumatoid arthritis patients (14 black, 151 white) who had received gold therapy to determine the relationship between HLA antigens and gold dermatitis, stomatitis, thrombocytopenia, and proteinuria. Dermatitis and stomatitis occurred in both black and white patients. Thrombocytopenia and proteinuria occurred only among the white patients studied. The absence of thrombocytopenia and proteinuria among the black patients was not statistically significant. Antigen HLA-DR7 was uncommon among black and white subjects with dermatitis (0 of 6 blacks, 4 of 48 whites), but this decrease in frequency was not statistically significant. Antigen HLA-DR3 was an important risk factor for thrombocytopenia (relative risk = 11.8, P = .0043) and proteinuria (RR = 5.8, P = .032). These results are consistent with previous studies of HLA-DR3 and gold toxicity. The only black patient with stomatitis possessed the A1B8DR3 phenotype. Future studies should examine whether the same HLA antigen confers risk of different gold toxicities in different racial groups, and whether there are HLA antigens that provide a protective effect.
2567598 Association of complement alleles C4AQ0 and C4B5 with rheumatoid arthritis in Japanese pat 1989 Jun We investigated polymorphisms of complement components C2, C4, and factor B (BF) in Japanese patients with rheumatoid arthritis (RA). The frequencies of C4AQ0 (32.1%) and C4B5 (35.9%) among RA patients were significantly higher than among healthy control subjects. C4B5 was strongly associated with HLA-Bw54, Bw59, DR4.1, and DQw4. C4AQ0 showed no association with HLA-Bw54 or Bw59, but there was weak association with HLA-DR4.1 and DQw4. The number of persons with both C4AQ0 and C4B5 was significantly higher in the RA patient group (relative risk 13.5). C2C and BFS were the most common alleles in RA patients, as well as in healthy control subjects. These data support the existence of 2 different putative susceptibility haplotypes (HLA-Bw54 or Bw59;C2C; BFS;C4A3;C4B5;DR4.1;DQw4 and C2C;BFS; C4AQ0;C4B1 or C4B2) in Japanese patients with RA.
3283986 [Value of ultrasonic diagnosis of popliteal cysts]. 1988 Ultrasonography of the knee joints in 55 patients with rheumatoid arthritis permitted diagnosing of popliteal cysts in 14 of them including 7 patients without any clinical symptoms. The method permitted measurements of cyst size and assessment of cysts before and after therapy. Ultrasonic B-scanning is a non-invasive, informative and reliable technique for the detection and assessment of popliteal cysts.
3592801 HLA haplotypes in non-familial rheumatoid arthritis. 1987 May The frequencies of HLA-A, B, C, DR, and BF haplotypes in 44 unrelated Caucasian patients with definite seropositive rheumatoid arthritis (RA) were compared with haplotype frequencies in controls. Overall, the patients had an increased risk for HLA-DR4, DR3, and DR2 antigens, but frequencies of certain DR4 or DR3 haplotypes were not increased, suggesting the importance of other HLA loci for the evaluation of risk. The presence of DR4 alone was not found to produce an increased risk for RA since the frequencies of certain DR4 haplotypes were similar in patients and controls. Increased frequencies of HLA-B18, DR4, HLA-B15, DR4, and HLA-A1, B8, Cw7, DR3 haplotypes were found in patients. RA susceptibility has been found to be associated with the last two haplotypes in some studies of multiple case families, suggesting that similar genetic mechanisms may underlie the disease in familial and sporadic forms.
2512862 Comparison of serum and synovial fluid concentrations of beta 2-microglobulin and C reacti 1989 Nov beta 2-Microglobulin and C reactive protein (CPR) were measured in 33 and 57 matched pairs of serum and synovial fluid (SF) respectively, from patients with active rheumatoid arthritis (RA). Serum beta 2-microglobulin concentrations were higher than in normal controls and the SF concentration was higher than the serum concentration on 25 of 33 occasions (76%), suggesting a local production of beta 2-microglobulin within the synovial membrane. There was a correlation between serum and SF concentrations of beta 2-microglobulin (r = 0.50). Patients' serum CRP concentrations in 57 samples were higher than in normal controls and were greater than in the matched SFs on 49 of the 57 paired samples (86%). In 18 samples CRP was absent in the SF, suggesting a local consumption or binding within the synovial membrane. Twenty four patients with RA given either sodium aurothiomalate or D-penicillamine for six months showed highly significant clinical improvements accompanied by reductions in serum and SF immunoglobulin concentrations and knee joint suprapatellar pouch synovial membrane T lymphocyte infiltrates. In this group of patients serum CRP, but not beta 2-microglobulin, fell significantly, but there were no significant changes in SF beta 2-microglobulin or CRP. These data suggest that serum and SF beta 2-microglobulin concentrations are not a useful index for determining the therapeutic response to sodium aurothiomalate and D-penicillamine and that serum rather than SF CRP concentrations are more helpful. The persistent raised serum and SF concentrations of beta 2-microglobulin probably reflect synovial inflammatory infiltrates, which are still considerable despite apparent clinical remission.
3820197 Patterns of in vitro aspirin hydrolysis rates in rheumatoid arthritis and systemic lupus e 1986 Oct In previous in vitro studies of normal human blood and in vivo canine studies an intracellular erythrocyte (RBC) esterase was identified which controlled the rate of aspirin (ASA) hydrolysis and thus modulated the duration of intact ASA survival and availability for transacetylations required for some therapeutic effects. In whole blood from 30 patients with systemic lupus erythematosus (SLE), 10 normal subjects, and 40 patients with active seropositive rheumatoid arthritis (RA), there were negative correlations between the hematocrit level and the ASA half-life in vitro: r = -0.50, -0.83, and -0.61, respectively. When ASA hydrolysis rates were normalized to approximate whole blood esterase content (k/Hb [min-1 X g-1 X dl] X 10(-4) the mean rate was most rapid in patients with RA (24.2 +/- 2.8) and lowest in patients with SLE (18.6 +/- 3.1), especially in those with recently active disease. To differentiate intracellular and extracellular factors, ASA hydrolysis rates were measured in washed RBC suspensions from similar groups. The mean ASA hydrolysis rate (k/10(6) RBC X 10(-3) was significantly lower in SLE RBC (7.72 +/- 0.81). In RBC from patients with RA the average rate (8.50 +/- 0.85) lay between the SLE group and controls (9.08 +/- 1.04). Thus, an erythrocyte esterase defect in SLE patients resulted in reduced ASA hydrolyzing capacity. In blood from patients with RA a small reduction in esterase activity was compensated by extracellular factors increasing ASA accessibility to the esterase.
2259898 OM-8980 and D-penicillamine in the treatment of rheumatoid arthritis. A 12-month double-bl 1990 Forty patients with active rheumatoid arthritis were included in this monocentre double-blind study comparing the therapeutic efficacy and safety of the immunomodulator OM-8980 with that of D-penicillamine. After 12 months of treatment, the parameters of Ritchie index, duration of morning stiffness, pain assessed by a visual analogue scale and categories, number of swollen joints, grip strength and erythrocyte sedimentation rate (ESR) were all significantly improved with OM-8980, as was the case for the Ritchie index, number of swollen joints and ESR with D-penicillamine. Significant intergroup differences were recorded for pain categories in favour of OM-8980 and for the Ritchie index and number of swollen joints in favour of D-penicillamine. The need for concomitant anti-inflammatory therapies and the assessment of efficacy by physicians and patients did not differ significantly between the two groups. OM-8980 was significantly better tolerated than D-penicillamine (5 patients with 5 side effects as compared with 12 patients with 16 side effects). OM-8980 can thus be regarded as an efficient and well-tolerated slow-acting drug for the treatment of rheumatoid arthritis.
2545638 Methotrexate serum-level determinations during low-dose therapy of rheumatoid and psoriati 1989 In 29 patients, 21 suffering from psoriatic arthritis and eight patients suffering from rheumatoid arthritis, methotrexate serum-levels were determined by means of radioimmunoassay. The aim of the investigation was to recognize an eventual dependence of the serum level of methotrexate on the total cumulative dose and to test the possibility of a concomitant therapy control. Beside the determinations of the serum levels of methotrexate, clinical examinations and laboratory tests were done at regular intervals. The values obtained showed no significant increase during the course of therapy compared to the values at the beginning of the treatment. Likewise no correlation to the total cumulative dose, the clinical picture or to the occurrence of side-effects could be found. Nor could any relationship between the changing of laboratory parameters and the methotrexate serum-levels be observed. No differences appeared in the methotrexate serum-levels during therapy of either rheumatoid or psoriatic arthritis patients. In conclusion it seems impossible to monitor a low-dose methotrexate therapy by continuous determinations of the serum levels of the drug.
1779087 Factors which contribute to fatigue associated with rheumatoid arthritis. 1991 Aug The purpose of this research was to identify the factors which people with rheumatoid arthritis (RA) believed contributed to their fatigue. A second purpose was to examine the relationships among identified factors and the sensation of fatigue. One hundred people with RA were asked to identify verbally factors which they believed contributed to their fatigue. The three most frequently identified factors included RA disease activity, disturbed sleep and increased physical effort. These factors were operationalized and measured as joint pain using the Modified McGill Pain Inventory, fragmented sleep through overnight electroencephalographic (EEG) sleep studies, and reduced physical ability using walking time and grip strength measures. Fifteen of the original subjects with RA and 12 age and gender matched control subjects completed the second phase of the research. Five of the RA subjects were experiencing a disease flare while the remaining 10 were either in remission or their disease was midly active. Those subjects in flare had significantly (P less than 0.01) more joint pain, significantly (P less than 0.05) more fragmented sleep, and significantly reduced functional capacity as measured through walking time (P less than 0.05) and grip strength (P less than 0.05) when compared to non-flare and control subjects. Fatigue levels of the subjects in flare were positively correlated with joint pain (r = 0.62), fragmented sleep (r = 0.42) and grip strength of the right hand (r = 0.52) and left hand (r = 0.88). Fatigue levels of non-flare and control subjects were negatively correlated with the majority of measured variables.(ABSTRACT TRUNCATED AT 250 WORDS)
2468336 Changes in lymphocyte infiltration of the synovial membrane and the clinical course of rhe 1989 Apr Multiple samples of synovial membrane were obtained by needle biopsy from 24 patients with rheumatoid arthritis (RA) before, and 1 year after, standard antirheumatic drug therapy was given. Changes in the immunohistologic features of the synovial membrane (read blindly) were compared with the clinical course of RA in each patient. A composite clinical index of disease activity (IDA) and spontaneous in vitro synthesis of IgM rheumatoid factor (IgM-RF) by blood mononuclear cells were also measured before and after treatment. In 16 patients (group A), the IDA indicated 26-69% improvement, and the values for spontaneous IgM-RF decreased substantially. In 8 patients (group B), the IDA indicated deterioration or no improvement, and the values for spontaneous IgM-RF were unchanged. In group A patients, the intensity of the T cell infiltrate decreased from a mean score of 1.3 to a mean score of 0.8 (P = 0.025). The ratio of T helper cells to T suppressor/cytotoxic cells was greater than or equal to 2:1 in 90% of group A patients before treatment, compared with 20% of these patients after treatment (P = 0.016), and the number of biopsy samples that contained identifiable B cells decreased from 36% before treatment to 7% after treatment. In group B patients, there were no changes in the intensity of T cell infiltration, the ratio of T helper cells to T suppressor/cytotoxic cells, or the number of biopsy samples with identifiable B cells.
2818656 Efficacy of physical conditioning exercise in patients with rheumatoid arthritis and osteo 1989 Nov A group of 120 patients with rheumatoid arthritis or osteoarthritis volunteered to be subjects for this study of aerobic versus nonaerobic exercise. Patients were stratified by diagnosis and randomized into an exercise program of aerobic walking, aerobic aquatics, or nonaerobic range of motion (controls). The retention rate for the 12-week program was 83%. Exercise tolerance, disease-related measures, and self-reported health status were assessed. The aquatics and walking exercise groups showed significant improvement over the control group in aerobic capacity, 50-foot walking time, depression, anxiety, and physical activity after the 12-week exercise program. There were no significant between-group group differences in the change scores for flexibility, number of clinically active joints, duration of morning stiffness, or grip strength. Our findings document the feasibility and efficacy of conditioning exercise for people who have rheumatoid arthritis or osteoarthritis.
1829436 [T-helper cell subsets in patients with inflammatory rheumatic diseases undergoing immunos 1991 Feb To determine the influence of immunosuppressive therapy on T-helper-cell subsets in patients with systemic lupus erythematosus and rheumatoid arthritis flow cytometric analysis was performed. Longitudinal studies showed reduced numbers of CD45R+CD4+ lymphocytes in patients treated with cyclophosphamide or azathioprine. Patients receiving steroids had low frequencies of CD29+CD4+ cells. The data suggest that cytotoxic drugs and steroids affect T-helper cells at different activation stages.
2278405 Right-to-left shunting through a patent foramen ovale caused by pulmonary hypertension ass 1990 Dec This case report presents a fifty-four-year-old woman with right-to-left shunt in the atrium. It seemed clinically at first that the shunt was due to atrial septal defect. However, she also had pulmonary disease associated with rheumatoid arthritis and Sjögren's syndrome. At autopsy atrial septal defect was not evident, but a patent foramen ovale and pulmonary artery disease were observed. This case suggests that pulmonary hypertension secondary to rheumatoid arthritis and Sjögren's syndrome could lead to right-to-left shunting through a patent foramen ovale.
2455616 Interferons in rheumatoid arthritis: alterations in production and response related to dis 1988 Aug Various markers associated with the production of and response to interferons (IFNs) were studied in patients with either inactive rheumatoid arthritis (RA) or active RA, and in healthy subjects. The IFN markers assessed were serum and synovial fluid (SF) levels, the activity in peripheral blood leukocytes (PBL) of (2'-5') oligoadenylate synthetase (OAS), and the production in vitro by PBL of IFN-alpha/beta in response to Sendai virus or Poly(I):Poly(C) as inducers, and of IFN-gamma using PHA or Con A as inducers. IFN activity, tested by antiviral assays using two different cell lines, was not demonstrable in the serum of any patient with RA. The activity of (2'-5') OAS in PBL, which may indirectly indicate exposure of leukocytes to IFN, was increased in RA compared with healthy subjects, more so in patients with inactive RA. The production of IFN-alpha/beta by PBL in response to Sendai virus was low in active RA but high in inactive RA, relative to production in healthy subjects. The production of IFN-gamma by PBL in RA was lower than in healthy subjects, more so in active RA. Thus inactive RA (remission status) is marked by evidence of PBL having been influenced by interferon and being a state of augmented inducibility to an IFN-alpha/beta stimulus, whereas active RA is associated with low inducibility of PBL to an IFN stimulus, but no evidence of IFN production in vivo. Our findings underscore the relevance of interferon to remission/activity in rheumatoid arthritis.
2259897 A comparison of overall health between patients with rheumatoid arthritis and a population 1990 Women with rheumatoid arthritis (RA) at a rheumatology outpatient clinic (PAT) were compared with women with RA in representative samples of the Gothenburg population (POP), and with non-arthritic women in this population (REF). Clinical routine measures disclosed substantial dysfunction in both RA groups. Their physical, psychosocial, and overall function, assessed by means of the Sickness Impact Profile (SIP), was more impaired than that of the REF. The PAT had a higher disease activity and worse overall health status than the POP. In definite and classical RA, a poorer SIP physical and overall function was noted in the PAT than in the POP group, despite similar mean age and mean disease duration. Women with probable RA in the POP group had worse SIP dysfunction than the REF, particularly regarding ambulation and personal care. The SIP was sensitive to variations in disease activity and comprehensively disclosed dysfunction better than routine clinical measures.
2561230 [The level of R proteins in reactive arthritis]. 1989 A total of 46 patients with reactive arthritides and 20 patients with rheumatoid arthritis (RA) were examined, as compared with 20 normal persons, for the blood serum content of the products of catabolic breakdown of cell receptors--R proteins (according to inhibition of the hemagglutination reaction between human red blood cells and anti-R-serum) and for conventional parameters of phagocyte function of leukocytes. The content of R proteins in patients with reactive arthritis and RA was found to be increased, and the phagocytic activity was discovered to be lowered. The changes in the parameters indicated depended on the disease entity and the disease course. The possible pathophysiological importance of changes in the level of R proteins in arthritides is discussed.
3032795 Alterations in neutrophil superoxide production following piroxicam therapy in patients wi 1987 Mar Twenty patients with classical rheumatoid arthritis were enrolled in a study to determine the effects of piroxicam therapy on neutrophil function as defined by chemotaxis and superoxide anion (O2-) production. T-lymphocyte chemotaxis was also evaluated in these patients. Leukocytes were obtained from these subjects initially, after two weeks of placebo treatment, and subsequently after four and 10 weeks of piroxicam therapy (20 mg, once daily). Responses were compared to simultaneously tested normal controls and to the patient's own cells obtained at the different time points. Studies showed that four and 10 weeks of piroxicam therapy resulted in significantly suppressed neutrophil O2- production in response to phorbol myristate acetate (PMA) and formyl methionyl leucyl phenylalanine (FMLP). O2- production in response to opsonized zymosan was not significantly affected after four weeks of therapy, but was significantly reduced after 10 weeks of therapy when compared to the patient's own cell response after two weeks of placebo treatment. Unlike O2- production, PMN random migration and chemotaxis in response to C5a or FMLP did not differ significantly from normal or untreated patient controls. Analysis of T-lymphocyte migration showed that T-cell random migration or migration to the chemokinetic agent, casein, was not significantly altered by piroxicam therapy. However, when T lymphocytes were tested for chemotaxis in response to lymphocyte-derived chemotactic factor for T cells (LCF), T cell migration was significantly suppressed after 10 weeks of therapy. Furthermore, when T cells from these subjects were cultured for 24 h, random migration was significantly reduced after four and 10 weeks of piroxicam therapy when compared to the patient prior to therapy, and migration in response to LCF was suppressed after four weeks of therapy when compared to normal controls. These data indicate that in patients with rheumatoid arthritis, treatment with piroxicam will significantly suppress PMN O2- production and may also alter the locomotor capacity of T lymphocytes. These actions may contribute to the antiinflammatory effects of piroxicam.