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

ID PMID Title PublicationDate abstract
2377862 [Dynamics of the blood flow in the joints of patients with rheumatoid arthritis--clinico-i 1990 Jan A certain stage-by-stage change in the regional blood flow was revealed in patients with rheumatoid arthritis depending on the degree of synovitis markedness. Having taken the volumetric blood flow and its intensity as the main criterion for the adequacy of regional hemodynamics, the authors propose to distinguish phases of compensation, subcompensation, and decompensation in the regional blood flow.
2182169 Comparative controlled trial of low-dose weekly methotrexate versus azathioprine in rheuma 1990 Apr Fifty-three patients with rheumatoid arthritis who required immunosuppressive therapy were commenced in a randomized trial comparing azathioprine to weekly oral pulse methotrexate. After an initial 24-week period, both groups had significantly improved from baseline measures of pain and functional capacity and there were no significant differences in clinical outcomes between the two groups. Laboratory variables of disease activity showed a significant improvement in haemoglobin and ESR in the methotrexate group. Subsequently, the patients were followed for up to 3 years. After one year, more than half of the patients in both groups had discontinued therapy due to inefficacy or adverse events. Adverse effects were more frequent in the patients treated with methotrexate, but withdrawal rates were similar in both groups. From these data, the probability of a patient continuing therapy with either agent for greater than 18 months is low.
3263133 Phenotypic analysis of synovial tissue and peripheral blood lymphocytes isolated from pati 1988 Oct Cytofluorometric analysis was performed to characterize the surface phenotype and activation status of freshly isolated synovial tissue lymphocytes (STL) and peripheral blood lymphocytes (PBL) from 7 patients with rheumatoid arthritis (RA). Proliferative synovium was enzymatically digested to obtain tissue-derived lymphocytes. Indirect immunofluorescent staining of patient PBL and STL with a variety of monoclonal antibodies failed to reveal a consistent alteration in the number of CD4+ (helper/inducer) PBL or STL. However, there was a significant decrease in the number of CD8+ (suppressor/cytotoxic) cells in rheumatoid STL (P less than 0.05). A significant reduction in the density of the T cell differentiation antigens CD3 and CD4 was observed in RA PBL and STL, compared with control PBL. These differences in antigen density were not seen when normal PBL were subjected to the same enzymatic digestion. Both RA PBL and STL manifested increased expression of HLA-DR antigens, without augmentation of interleukin-2 receptor expression. Alterations in the expression of the T cell differentiation antigens and activation antigens by patient PBL closely paralleled the abnormalities observed in STL. In contrast, STL of patients with RA exhibited an increase in the expression of the adhesion-related glycoproteins (leukocyte function-associated 1 [LFA-1] and very late activation 1 [VLA-1] antigens), not observed with autologous PBL. These studies demonstrate that lymphocytes isolated from the synovial tissues of RA patients bear an activated phenotype, exemplified by the modulation of CD3 and CD4 and the expression of HLA-DR.(ABSTRACT TRUNCATED AT 250 WORDS)
3075077 Role of cytokines in rheumatoid synovitis. 1988 Although the chronic inflammatory reaction in rheumatoid synovitis appears to be stimulated by an as yet unidentified antigen, the mononuclear cell infiltration is to a large extent accomplished through the nonspecific action of cytokines and growth factors acting as (1) chemotactic agents for the emigration and ecotaxis of monocytes and lymphocytes, (2) upregulators of endothelial cells for the binding of lymphocytes and monocytes to the endothelium of postcapillary venules prior to emigration and (3) angiogenic agents for the proliferation of the microvasculature, and as a result, the proliferation of the synovial membrane. The synovial lining layer may play an important part in this process by stimulating the infiltration of the synovial tissue with "exudate macrophages" as a necessary step in the development of lining layer hyperplasia. Evidence for the capacity of the cytokines to mediate chronic synovitis is provided by the well-known observation that intraarticular injection of cytokines, particularly IL-1, produces both acute and chronic synovitis in the experimental animal.
3320160 Effect of total lymphoid irradiation on IgE antibody responses in rheumatoid arthritis and 1987 Dec Thirteen patients with rheumatoid arthritis and four patients with systemic lupus erythematosus and nephritis were treated with total lymphoid irradiation because of severe disease refractory to other forms of treatment. Serum samples before and after irradiation were tested for changes in total serum IgE and for changes in specific IgE antibodies to ryegrass pollen, dust mite, cat dander, and Alternaria. There were no statistically significant changes in total or specific IgE from lymphoid irradiation in these patients. The therapy caused a significant decrease in circulating total lymphocyte and Leu-3 (helper/inducer) T-lymphocyte counts. Therefore, reduction in circulating levels of helper/inducer T cells does not appear to influence preexisting levels of IgE antibodies.
3497421 T cell subsets in the blast cell population in phytohemagglutinin-stimulated peripheral bl 1987 The immunomodulatory T4/T8 ratio was studied in the total and activated lymphocyte populations by a method combining visualisation of 3H-thymidine incorporating blasts with autoradiography (AR) with simultaneous identification of the respective lymphocyte subsets using monoclonal antibodies in avidin-biotin-peroxidase complex (ABC) staining. In rheumatoid arthritis synovial fluid the activated T4/T8 ratio (calculated from T cells in the S phase of the cell cycle) was significantly different from the total T4/T8 ratio (calculated for all the T cells) (0.45 +/- 0.05 versus 0.69 +/- 0.05, P less than 0.01). Similarly, the activated and total T4/T8 ratios were also significantly different in the phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cell cultures at days 3 and 5.
3752419 A longitudinal study of the influence of azathioprine on natural killer cell activity. 1986 May Natural killer (NK) cell activity against K562 target cells was studied in six patients with definite or classical rheumatoid arthritis before and during treatment with azathioprine. Azathioprine induced suppression of NK cell activity, but treatment with azathioprine for 5-8 months was necessary before NK cell activity was completely suppressed. In vitro incubation of mononuclear cells from a healthy donor with azathioprine or 6-mercaptopurine in concentrations not reducing cell viability did not inhibit NK cell activity, nor did sera from patients treated with azathioprine for more than 6 months.
2285754 Self-reported fatigue in rheumatoid arthritis. A pilot study. 1990 Sep The purpose of this pilot study was to examine the symptom of fatigue in rheumatoid arthritis. The instruments used included the Profile of Mood States, fatigue and pain visual analog scales, and an interviewer's assessment of respondent fatigue. The results indicated that fatigue was a significant problem in this sample; fatigue was positively associated with depression, pain, and poorer overall mood state; and the three measures of fatigue produced congruent reports of fatigue.
2946352 Joint disorders at ages 70, 75 and 79 years--a cross-sectional comparison. 1986 Nov The prevalence of back and joint complaints and of rheumatoid arthritis (RA), chondrocalcinosis (CC) and osteoarthritis (OA) was studied in three representative population subsamples aged 70, 75 and 79 years. The prevalence of back pain was 38% and of joint complaints 40%, both significantly higher in females. The prevalence of RA was not significantly different between the age groups. Chondrocalcinosis increased with age in females. Radiographic and clinical OA of knees was less prevalent with increasing age. Symptoms of wrist and finger OA occurred in 1-4% of females but not males. Enlargement of DIP joints occurred in 50% of females and 25% males. Radiographic OA of first MCP joints was more prevalent with age in males but not females. Obesity correlated with radiographic OA of knees in females. Clinical and radiographic OA of fingers and knees did not correlate with previous strenuous occupations.
3498578 Lymphokine-activated killer cell activity in rheumatoid arthritis. 1987 Jun The lymphokine-activated killer (LAK) cell activity in the peripheral blood of 23 patients with rheumatoid arthritis has been studied. Two control groups comprised (a) nine patients with another chronic inflammatory disease (sarcoidosis) and (b) 19 normal healthy volunteers. The LAK activity induced by human recombinant IL-2 was very similar in controls and patients with rheumatoid arthritis but was significantly decreased in patients with sarcoidosis, although the frequency of LAK-cell precursors measured using a limiting dilution assay was comparable in all three groups. The DNA synthetic response of peripheral blood mononuclear (PBM) cells to IL-2 was slightly decreased in patients with both rheumatoid arthritis and sarcoidosis as compared to controls, but this decrease was not statistically significant. Spontaneous DNA synthesis in PBM cells cultured in the absence of IL-2 was essentially identical in all three groups. We conclude on the basis of these results that the higher risk of non-Hodgkin's lymphomas in patients with rheumatoid arthritis cannot be attributed to an impairment of LAK activity. Furthermore, the doses of gamma-irradiation, which abolished the 'background' cytotoxicity of PBM cells cultured without IL-2 and also blocked effectively both spontaneous and exogenous IL-2-dependent DNA synthesis, had little effect on the generation of LAK activity. These observations are discussed in regard to the role of non-specific cytotoxic cells and the therapeutic efficacy of antiproliferative drugs in rheumatoid arthritis.
2678397 [Levels of the C 4 component of the complement, lactoferrin and leukocytic thermostabile a 1989 Apr The authors studied the dynamics of C4-component of complement (C4), lactoferrin (LF), leukocytic thermostable alpha-glycoprotein (LT alpha G) in the blood serum of 54 patients with rheumatoid arthritis, 32 patients with systemic lupus erythematosus, 8 patients with systemic vasculitis under the effect of hemosorption (HS), enterosorption (ES) and also immunosuppressants (IS). In severe forms of systemic rheumatic diseases the blood serum exhibits a decreased content of C4 but an elevated level of LF and LT alpha G. It has been established that HS is more active than ES or IS, and it influences the mechanisms of humoral immunity. This finds its expression in normalization of C4 level. The favourable clinical effect of HS correlates with a decrease in the level of LF and LT alpha G in the blood serum of patients during treatment.
2499030 DNA synthesis in CD4- and CD8-positive cells in synovial fluid of patients with reactive a 1989 The occurrence of MHC class I antigens and microbial antigens derived from the triggering infection of the diseased joints in reactive arthritis (ReA) seems to set the stage for local immune activation. In this report activated lymphocytes are demonstrated by using an avidin-biotin-peroxidase complex (ABC) method combined with autoradiography that identifies DNA synthesis and, thus, activation. Most of the activated T lymphocytes in reactive arthritis were found to belong to the CD8 suppressor/cytotoxic T-lymphocyte subset. In striking contrast, the majority of the activated T lymphocytes detected in rheumatoid arthritis (RA) synovial fluid belonged to the CD4 helper/inducer subset. These findings agree well with the assumption that CD8-positive cells identify the foreign antigen in the context of class I antigens, whereas CD4-positive cells are found to be associated with the recognition of MHC locus II coded HLA antigens.
2373064 Helplessness and depression in rheumatoid arthritis. 1990 Depression is common in rheumatoid arthritis (RA) populations and has been hypothesized to result from patients' belief that they cannot control their disease or its impact. In a sample of 106 patients with RA, we found that scores on a measure of helplessness mediated the relationship between severe, disabling RA and depression. Further, this association was independent of the previously demonstrated correlation between cognitive distortion and depression in RA patients. Thus, both helplessness and cognitive distortion may be important factors in the development and treatment of depression among RA patients.
2781480 [Interferon in rheumatoid arthritis]. 1989 The paper is concerned with the role played by interferon (IF) in rheumatoid arthritis (RA). The content of IF was measured in the patients' blood serum and the possibility of the use of the preparations of exogenous interferon for the treatment of RA patients was demonstrated. Assay of serum IF in RA patients showed that its content did not exceed normal. The results of the treatment with IF preparations has demonstrated their beneficial effect on certain parameters. Further study of the role played by IF in the management of rheumatic diseases is required in order to develop the drug doses and schedules for the treatment.
3683118 [Hemostatic homeostasis following radio-synovectomy in rheumatoid arthritis]. 1987 Nov Platelet functional activity, plasma coagulation and fibrinolysis were studied in patients with rheumatoid arthritis (RA) against a background of various therapeutic modalities. Therapy with non-steroid anti-inflammatory agents resulted in an increase in platelet and plasma coagulating activity and inhibition of fibrinolysis. An insignificant rise of disaggregation of platelet aggregates was noted 2 weeks after intraarticular administration of 198Au against a background of therapy with non-steroid anti-inflammatory agents. Mydocalm incorporated in a dose of 1-2 mg/kg in the therapeutic scheme did not change significantly blood coagulation indices.
2344209 Concentrations of glycosaminoglycans in synovial fluids and their relation with immunologi 1990 May The dimethylmethylene blue assay showed higher concentrations of glycosaminoglycans in many synovial fluids from patients with rheumatoid arthritis (RA) than in autologous sera or sera or synovial fluids from normal subjects. These results were taken to suggest that the glycosaminoglycans in RA synovial fluid were abnormally raised and derived from cartilage. To discover what stimulated such glycosaminoglycan release in RA joints relations were sought between synovial fluid concentrations of glycosaminoglycans and immunological and inflammatory mediators. It was shown that RA synovial fluid glycosaminoglycan concentrations correlated with synovial fluid C3d concentrations but not with synovial fluid rheumatoid factor concentrations, polymorphonuclear leucocyte numbers, myeloperoxidase concentrations, or the ability of the synovial fluids to release free radicals from normal polymorphonuclear leucocytes. A correlation was found between synovial fluid C3d and interleukin 1 concentrations as judged by both lymphocyte activating factor activity and immunoassay, but no significant correlation was detected between interleukin 1 and glycosaminoglycan concentrations. It is suggested that in the rheumatoid joint locally produced cytokines, in addition to interleukin 1, together stimulate glycosaminoglycan release from cartilage and render it vulnerable to attack by other processes.
2213775 A self-report articular index measure of arthritic activity: investigations of reliability 1990 Aug A self-report measure of rheumatoid arthritic activity developed from the articular index described by Thompson, Silman, Kirwan, and Currey (1987), was tested for reliability, validity, and sensitivity to therapeutic change. Concurrent validity was demonstrated by a significant correlation, (ICC = 0.83) between the self-report measure and a standard Thompson index completed by a rheumatologist. Test-retest reliability was demonstrated by significant correlations (ICC = 0.88, ICC = 0.77) between repeated administrations of the self-report form in 2 independent samples. The self-report measure demonstrated sensitivity to therapeutic change when completed by patients both before and after intraarticular corticosteroid injection. The rheumatologist's index correlated significantly with C-reactive protein but the self-report form did not.
2604525 [Evolutive atlanto-axial luxation revealing chronic inflammatory rheumatism in children]. 1989 Nov Atlanto-axial luxation in uncommon in chronic arthritis in childhood, especially early in the course of the disease. One case is described in which atlanto-axial luxation occurred early. Computed tomographic myelography showed the cervico-medullary compression which was treated by transoral anterior decompression and posterior occipito-cervical fusion.
3491586 Genetic structure of the population with rheumatoid arthritis in north east England: a gen 1986 Nov Clinically and immunologically rheumatoid arthritis (RA) is possibly a heterogeneous disorder. Despite numerous efforts clearer definition of this heterogeneity has been of limited success. Measurements of rheumatoid factor (RF) and antinuclear antibodies (ANA) by conventional methods define subpopulations of patients with RA and in a few recent studies an association of human leucocyte antigens (HLA) undoubtedly indicates the immunogenetic differences in the susceptibility of RA patients with different status of autoantibodies. The studies on a few isolated non-HLA genetic markers in RA are controversial. To understand the role of genetic factors in susceptibility 24 single gene characters other than HLA were investigated in 225 patients with RA classified by humoral status (presence or absence of RF and ANA) into three groups and in 104 healthy control individuals from the north east of England. Locus by locus comparison suggested associations of MN, Lewis, and Bf system with RF positive patients. Although the associations with MN and Lewis blood groups require further investigations, the involvement of the Bf locus is in agreement with the immunological component of the disease suggested by HLA associations and it could be due to the phenomenon of linkage disequilibrium. Measures of genetic distance applied to the subpopulations of patients with RA, divided according to the presence or absence of humoral factors, suggest that RF+ ANA+, RF- ANA-, and RF+ ANA- subgroups are distinct genetic diseases, each affecting a different subsection of the population which is genetically distinct. Such genetic heterogeneity may suggest a different pathogenetic mechanism for each of these subpopulations of rheumatoid arthritis.
3492027 Anti-C1q affinity isolated circulating immune complexes correlate with extra-articular rhe 1986 Circulating immune complexes (CIC) were isolated from sera of 35 patients with rheumatoid arthritis (RA) by a two-step method using 2% polyethylene glycol precipitation and anti-C1q affinity chromatography. By this method CIC were exclusive to 19 patients with vasculitis, nodules, or Sjögren's syndrome. Levels of CIC did not correlate with the severity of synovitis but reflected the extent of extra-articular disease. Furthermore, in four patients with persistent severe synovitis observed over a period of 4 to 16 months, the levels of CIC paralleled changes in extra-articular disease. Despite such additional evidence, whether the relationship between CIC and tissue injury is causative or consequential remains unresolved.