Browse

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

ID PMID Title PublicationDate abstract
1304740 Cytokine inter-relationships and their association with disease activity in arthritis. 1992 Nov In order to investigate the relationships between cytokine production and arthritic disease we have determined the concentrations of immunoreactive interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, tumour necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), IFN-gamma, and soluble IL-2-receptor (sIL-2R), as well as bioactive IL-1 and IL-6, in synovial fluids (SF) and plasma of patients with a variety of arthritides. Careful assay revealed only minimal concentrations of IL-1, particularly its biologically active form, in SF. No IL-1 was detectable in the plasma of patients that had IL-1 in their SF. Concentrations of both immunoreactive IL-1 beta and TNF-alpha in SF of rheumatoid arthritis (RA) patients were significantly higher than those in SF from patients with other inflammatory arthritides or osteoarthritis (OA). IL-6 and sIL-2R concentrations in both SF and plasma were higher in RA patients than in OA patients, and were significantly correlated. Approximately half of the SF from patients with all arthropathies contained detectable IFN-alpha, whilst IFN-Y was present in less than 10%. There were significant associations between IL-6, sIL-2R, IL-1 beta, TNF-alpha and IFN-alpha. The concentration of these cytokines, where detectable, was also related to leukocyte counts in the SF, as well as to parameters assessing local and systemic disease activity. Although IL-6 was the cytokine most clearly related to other cytokines, and to parameters assessing disease activity, the relationship between general articular disease activity and IL-6 was only evident in patients with arthropathies other than rheumatoid arthritis.
8511598 Lymphedema of the upper limb in patients with psoriatic arthritis. 1993 Apr Upper limb lymphedema occurs rarely in rheumatoid arthritis (RA) but has been reported only once in psoriatic arthritis (PsA). The pathogenesis is unknown. This study describes four patients (three women) with upper limb lymphedema, chronic symmetrical polyarthritis, and psoriasis. Three were seronegative, diagnosed PsA; one was seropositive. Age ranged from 39 to 64 years, duration of psoriasis was 6 to 42 years, and duration of arthritis was 6 to 12 years. Onset of lymphedema was unrelated to the extent or severity of arthritis, and no other cause for this condition was identified. Radiological appearances ranged from mildly abnormal to advanced joint destruction, but carpal disease was prominent in all patients. Lymphoscintigraphy was abnormal in three subjects. Lymphedema became bilateral in two and was associated with radiological progression of arthritis. Disease-modifying therapy produced improvement of lymphedema in two patients and correction of the lymphoscintigraphic abnormality in one. This study describes upper limb lymphedema in patients with PsA and suggests that local synovitis may play a role in its pathogenesis.
7705481 Initial arthritic lesions induced by immunization with type II collagen in Lewis rats. 1995 Jan Lewis rats were immunized with an intradermal injection of type II collagen to study the time course of arthritic lesions. Serum type II collagen antibody was detected 9 days after immunization. Increased paw volume in the hind limbs was noted on day 11. Histopathologically, proliferation of synovial lining cells was observed on day 11 and typical lesions similar to those of human rheumatoid arthritis were noted on day 18.
8252804 The putative oncoprotein DEK, part of a chimera protein associated with acute myeloid leuk 1993 Dec The 45-kD autoantigen associated with juvenile rheumatoid arthritis (JRA) has been isolated from HeLa cell nuclei and purified about 2500-fold to near homogeneity in a five-step chromatographic procedure. Purification of the antigen was monitored by immunoblot assays using a nearly monospecific anti-45-kD serum from a child with JRA. Tryptic peptide mapping and partial amino acid sequencing of the purified 45-kD antigen demonstrated its identity with the DEK protein. DEK is a 43-kD protein of unknown function expressed by the putative oncogene dek located on chromosome 6. As a result of a (6;9) translocation offociated with a rare subtype of acute myeloid leukaemia a chimeric protein containing most of DEK amino acids at the N-terminus is found in leukaemic cells (von Linden et al., Mol Cell Biol. 1992; 12: 1687-97). The 43-kD DEK was detected by immunoblotting with serum from a patient with JRA in a variety of rat tissues, and was most abundant in the spleen and in bone marrow.
7694228 Intraarticular alpha 2-macroglobulin complexes and proteolytic activity in children with j 1993 Aug In juvenile rheumatoid arthritis (JRA), it is likely that the release of proteolytic enzymes from activated synovial fluid neutrophils overwhelms the major protease inhibitor, alpha 2-macroglobulin (alpha 2-MG), and leads to cartilage destruction. Due to the unique nature of the alpha 2-MG-protease complex, proteolytic function is maintained until the complex is cleared. In this study, we sought to determine the concentration of alpha 2-MG-protease complexes in synovial fluid of patients with JRA, the proteolytic activity found in their synovial fluid, and whether the alpha 2-MG complexes are associated with increased proteolytic activity. The JRA patients' synovial fluids had complex levels of 217.0 +/- 192.2 nmol/L--significantly elevated compared with plasma values (p < 0.001) and with control synovial fluid (p < 0.05). Elastase activity (almost entirely neutrophil elastase) was detected in all JRA synovial fluid samples (mean 2.9 +/- 2.6 mg/L) and significantly correlated with alpha 2-MG-complex values (r = 0.67, p < 0.01). Synovial fluid tryptic activity was detectable in all JRA patients but did not significantly correlate with alpha 2-MG complexes (r = 0.53, p > 0.05). Seventy-four percent of total elastase activity and 41% of total tryptic activity were contained in the alpha 2-MG-complex fractions. We suggest that the increased concentration of synovial fluid alpha 2-MG complexes with retained elastase activity contributes to continued proteolysis and joint destruction and may affect the subsequent disease course through its role as a modulator of IL-6.
8970491 Self-reports and general practitioner information on the presence of chronic diseases in c 1996 Dec OBJECT: The object of the study is to investigate the (in)accuracy of patients' self-reports, as compared with general practitioners' information, regarding the presence of specific chronic diseases, and the influence of patient characteristics. METHODS: Questionnaire data of 2380 community-dwelling elderly patients, aged 55-85 years, on the presence of chronic non-specific lung disease, cardiac disease, peripheral atherosclerosis, stroke, diabetes, malignancies, and osteoarthritis/rheumatoid arthritis were compared with data from the general practitioners, using the kappa-statistic. Associations between the accuracy of self-reports and patient characteristics were studied by multiple logistic regression analyses. RESULTS: Kappa's ranged from 0.30 to 0.40 for osteoarthritis/rheumatoid arthritis and atherosclerosis, to 0.85 for diabetes mellitus. In the multivariate analyses, educational level, level of urbanization, deviations in cognitive function, and depressive symptomatology had no influence on the level of accuracy. An influence of gender, age, mobility limitations, and recent contact with the general practitioner was shown for specific diseases. For chronic non-specific lung disease, both "underreporting" and "overreporting" are more prevalent in males, compared to females. Furthermore, males tend to overreport stroke and underreport malignancies and arthritis, whereas females tend to overreport malignancies and arthritis. Both overreporting and underreporting of cardiac disease are more prevalent as people are older. Also, older age is associated with overreporting of stroke, and with underreporting of arthritis. The self-reported presence of mobility limitations is associated with overreporting of all specific diseases studied, except for diabetes mellitus, and its absence is associated with underreporting, except for diabetes mellitus and atherosclerosis. Recent contact with the general practitioner is associated with overreporting of cardiac disease, atherosclerosis, malignancies and arthritis, and with less frequent underreporting of diabetes and arthritis. CONCLUSIONS: Results suggest that patients' self-reports on selected chronic diseases are fairly accurate, with the exceptions of atherosclerosis and arthritis. The associations found with certain patient characteristics may be explained by the tendency of patients to label symptoms, denial by the patient, or inaccuracy of medical records.
8838527 Juvenile psoriatic arthritis: followup and evaluation of diagnostic criteria. 1996 Jan OBJECTIVE: To describe the course of juvenile psoriatic arthritis (JPsA) defined by the "Vancouver Criteria." METHODS: A retrospective review of JPsA in 63 children, (44 girls, median age at onset 4.5 yrs; 19 boys, median age at onset 10.1 yrs) who fulfilled the Vancouver Criteria, as follows. Definite JPsA: arthritis with psoriasis, or arthritis with 3 of 4 minor criteria (nail pits, dactylitis, psoriasis-like rash, family history of psoriasis); probable JPsA: arthritis with 2 of the minor criteria. RESULTS: At last followup, 50 children had definite JPsA and 13 had probable JPsA. Rheumatoid factor was absent in all; antinuclear antibody was present in 50%. Thirty-eight children were followed for > 5 yrs, 18 for > 10 yrs, and 7 for > 15 yrs. Forty-four children had active arthritis; 32% were in functional class I, 38% in class II, 22% in class III, and 8% in class IV. Of the 46 patients with oligoarticular onset, 21 remained oligoarticular, and 25 became polyarticular. Arthritis in the small joints of the hands and feet increased in frequency, with arthritis eventually occurring in proximal interphalangeal joints in 63%, metacarpophalangeal or metatarsophalangeal joints in 55%, and distal interphalangeal joints in 27%. Dactylitis occurred in 35%, most commonly in 2nd toes and index fingers. Nine patients (14%) developed chronic anterior uveitis. Eleven of 24 patients (46%) who initially had probable JPsA evolved to definite JPsA after a median of 2.1 yrs. Five developed psoriasis and the remainder developed additional minor criteria. The 13 patients with a current diagnosis of probable JPsA did not differ significantly from the 50 patients with definite JPsA with respect to number of joints involved at onset or during the disease course. Patients with psoriasis (n = 41) did not differ from those with definite JPsA without psoriasis (n = 9) with respect to the number of joints involved at onset or during the disease course, functional class, or need for 2nd line therapy. CONCLUSION: JPsA defined by the Vancouver Criteria is a relatively common chronic arthropathy of childhood that differs clinically, serologically, and genetically from both juvenile rheumatoid arthritis and juvenile ankylosing spondylitis.
8905111 Macrophage reactions in septic arthritis. 1996 With the aid of monoclonal antibodies, macrophages can be split into functionally distinct subpopulations on the basis of their phenotype. Absence of macrophage subtypes has been noted in chronic inflammatory processes, e.g. posttraumatic osteomyelitis, rheumatoid arthritis and sarcoidosis. In the inflammatory focus of acute septic arthritis (n = 13 patients) however, macrophages constitute the majority of immunocompetent cells. The inflammatory macrophage subtype 27E10 was clearly present in increased numbers in 11 of 13 biopsies from the inflammatory foci, showing the effector task of this subtype in synovial resistance. The anti-inflammatory macrophage subset RM3/1 was present in increased numbers in biopsies of infected tissue and the surrounding soft tissue. The occurrence of 25F9-positive macrophages, typical of the late phase of inflammation, varied widely in the biopsies.
1639172 The humoral immune response to heat shock proteins. 1992 Jul 15 Humoral immune reactions to heat shock proteins (hsp) from microorganisms are one aspect of microbial infections in humans. The production of antibodies which are specific to epitopes present on procaryotic hsp leads also to the appearance of cross-reactive serum antibodies in the host organism that react with human hsp. This article discusses the consequences of such autoreactive antibodies for the host in context with the development of immune tolerance and autoimmune diseases, especially rheumatoid arthritis (RA), and in experimental animal models for arthritis such as adjuvant arthritis in rats. On the basis of epitope cross-reactivity between hsp and other host proteins, a hypothesis is presented for the development of autoimmune disease following the production of hsp-specific antibodies.
8819622 Dialysis treatment in children with amyloidosis due to juvenile rheumatoid arthritis. 1996 Jan Rapid deterioration of renal function in amyloidotic children may be due to progression of amyloidosis or exacerbation of chronic renal failure (CRF). Continuous ambulatory peritoneal dialysis (CAPD) is superior to hemodialysis (HD) both in end-stage renal disease and in exacerbations of CRF in amyloidosis. A better supply of protein and easier control of hypertension are possible on CAPD, while HD is associated with the risk of hypovolemia episodes, cardiovascular disturbances and bleeding connected with heparinization.
1458683 Induction of adjuvant arthritis in mice. 1992 Dec Adjuvant arthritis, induced by injections of Freund's complete adjuvant into the footpads of some rat strains, has been recognized as a useful animal model for many years. There has, however, been notable lack of success in reproducing this model in other species. We now describe the development of adjuvant arthritis in healthy strain mice approximately 2 months after injection of Freund's complete adjuvant. Although the clinical appearance of the mice and the joint histopathology closely resemble the adjuvant arthritis reported in the rat, we were unable to detect rheumatoid factor in sera from the affected animals. In parallel studies of T cell proliferation, affected animals responded to some mycobacterial antigens but not to the 65-kD heat shock protein of Mycobacterium tuberculosis, suggesting that some other epitope is important in the development of the disease.
8335082 A decrease in the estimated frequency of the extended HLA haplotype B18 CF130 DR3 DQw2 is 1993 Jul 5 Extended HLA haplotypes frequencies were estimated from the HLA, C2, Bf and C4 phenotypes of 74 patients with non-insulin-dependent diabetes (NIDD), 92 with juvenile rheumatoid arthritis (JRA), 44 with Berger's disease (BD), 83 with insulin-dependent diabetes (IDD), and 140 healthy controls. The extended HLA haplotype B18 CF130 DR3 DQw2, which is common (around 10% phenotype frequency) in healthy Spaniards and in other populations of paleo-North African origin, was found to be significantly less frequent in NIDD, JRA and BD, whereas its frequency was normal in IDD (although DR3 DQw2 haplotypes were increased in the latter disease). These data support the existence of a common HLA-linked pathogeneic mechanism in NIDD, JRA and BD, and point to a genetic difference between IDD and NIDD at the HLA level. This effect is readily detectable in our population because the uncommon BfF1 allele marks that haplotype instead of the more common BfS, which marks B8 CS01 DR3 DQw2 in other Caucasians. Our results support the hypothesis of strong selective pressures operating at the HLA level to preserve extended HLA haplotypes with advantageous gene sets from dilution by crossing-over. Imbalanced incomplete haplotypes may give rise to inappropriate T-cell repertoire selection in the thymus and/or antigen handling in the periphery, and be partly responsible for the pathogenesis of certain HLA-linked diseases (i.e. NIDD, JRA, and BD).
1387614 Limited heterogeneity of T cell receptor variable region gene usage in juvenile rheumatoid 1992 Sep The aim of this study was to determine whether synovial fluid (SF) T cells in patients with juvenile rheumatoid arthritis (JRA) are restricted in their T cell receptor (TcR) gene repertoire. The quantitative polymerase chain reaction (QPCR) was used to compare the transcription of V beta and V alpha gene families in freshly isolated SF T cells, in interleukin-2 receptor-positive (IL-2R+) T cells and in peripheral blood (PB) T cells from 18 patients. Significantly less V beta families are detected in SF when compared with PB (p greater than 0.0003). The TcR V beta gene usage by IL-2R+ T cells was even less heterogeneous when compared with freshly isolated SF T cells (p greater than 0.0002). Freshly isolated SF T cells from the left and the right knees of four patients transcribed the same V beta families. Furthermore, we demonstrate that in SF the distribution of certain TcR V beta gene segments in CD4+ and CD8+ T cells differed from that in PB of the same patient. The TcR V alpha usage was studied in IL-2R+ T cells from six patients who had shown restriction in their SF TcR V beta gene usage. Only two to five TcR alpha transcripts were detected in three of these patients while a broad TcR V alpha usage was seen in the other three patients. Sequence analysis of the SF V beta 20 cDNA clones generated from the IL-2R+ T cells of two patients demonstrated an oligoclonal expansion. Taken together, our data could indicate an antigen- and/or superantigen-driven expansion of selected T cells in the synovial compartment.
8010862 [Pericarditis disclosing at adult age recurrent Still's disease in childhood]. 1993 Nov A 29 year old patient with a history of juvenile rheumatoid arthritis had a recurrence 12 years later, presenting as pericardial effusion with cardiac tamponade. Cardiac tamponade is a rare complication of Still's disease. To the author's knowledge, it has never been described as the mode of presentation of adult Still's disease. The diagnostic difficulties and inefficacy of non-steroid anti-inflammatory agents are illustrated by this case.
7558921 Interaction between HLA-DR and HLA-DP, and between HLA and interleukin 1 alpha in juvenile 1995 Apr EOP-JRA is an autoimmune disease that displays associations with DPB1*0201, DR8, DR5, and DR6, as well as an association with IL1A2 (a variant of IL1 alpha gene, not HLA linked). The purpose of this study was to analyze interactions between these genetic factors. We studied 103 EOP-JRA patients, 181 random controls, and 69 DR8-positive controls. We found a positive interaction between DPB1*0201 and the DRB1 alleles encoding DR3, DR5, or DR6, but not DR8. In addition, we found evidence for an interaction between IL1A2 and DR(3, 5, or 6) and DP2, but not DR8. We interpret the data to suggest heterogeneity in the HLA-associated pathogenic mechanisms of EOP-JRA.
1640195 Function of terminal ileum in patients with Yersinia-triggered reactive arthritis. 1992 Jul In order to study the function of the intestinal epithelium in the terminal ileum, the Schilling test was performed in 10 patients with Yersinia-triggered reactive arthritis, in 10 patients who had recovered from Yersinia enteritis without complications, and in five patients with rheumatoid arthritis treated with non-steroidal anti-inflammatory agents. The Schilling test indicates absorption of vitamin B12 in the terminal ileum, i.e. the area affected by Yersinia and inflamed in patients with reactive arthritis. The findings obtained demonstrate increased uptake through the epithelium in this area of the intestine in patients with Yersinia-triggered reactive arthritis. There are two possible explanations. First, Yersinia infection may have a long-term effect on the gut mucosa. Secondly, some individuals may, at the level of the terminal ileum, show enhanced absorption of vitamin B12 and/or other substances such as microbes or their components, resulting in increased susceptibility to certain infections.
8835627 Effects of cytogenin on spontaneous arthritis in MRL/1 mice and on pristane-induced arthri 1995 Cytogenin, 8-hydroxy-3-hydroxymethyl-6-methoxyisocoumarin, has low cytotoxicity on murine and human tumour cells in vitro. It augments or suppresses phagocytosis of macrophages and lymphocyte proliferation. It has been reported that cytogenin has a potent inhibitory effect clinically on adjuvant arthritis in Lewis rats and on type II collagen-induced arthritis in DBA/1J mice. Our experimental findings provide evidence that cytogenin has beneficial effects on spontaneous polyarthritis in MRL/1 mice and pristane-induced arthritis in DBA/1J mice. The results suggest that the mode of the anti-arthritic action of cytogenin is different from those of NSAIDs; although the precise mode of action remains unclear, cytogenin may become an excellent therapeutic agent for rheumatoid arthritis.
1525633 Ophthalmological screening in juvenile arthritis: should the frequency of screening be bas 1992 Sep Chronic iridocyclitis (CI) may complicate juvenile chronic arthritis (JCA) and if left untreated may cause significant ocular impairment. It is usually not symptomatic and diagnosis relies on slit lamp biomicroscopy. It is unclear how often children with JCA should be screened for this complication. From a review of the literature, the following recommendations could be made, although these require scientific validation. All children with JCA should have at least one adequate slit lamp examination as soon as possible after diagnosis of the arthritis. If CI is detected then appropriate treatment and follow up should be determined by the ophthalmologist. If CI is not detected initially, all children with JCA should be screened by slit lamp examinations every 3-4 months for the first 5 years after arthritis onset. After 5 years, CI screening could be stopped. The only exceptions would be arthritic children at low risk for CI, including systemic onset JCA, juvenile spondyloarthropathy and juvenile onset rheumatoid arthritis, who do not need to be screened if the initial slit lamp examination is normal.
1613734 Binding characteristics of human hybridoma IgG and IgM rheumatoid factors: influence of Ig 1992 Jan The interaction of human monoclonal rheumatoid factors (RF) with the Fc portion of IgG is complex. We have investigated the influence of the nature of the antigen (Fc) on the binding of hybridoma-generated RF derived from patients with rheumatoid arthritis or systemic lupus erythematosus. For IgM RF, the interaction is strongly influenced by the primary structure of the Fc with little or no effect of the carbohydrate, which is positioned at amino acid 297 in the gamma-2 domain. In contrast, our preliminary data suggest that IgG RF binding is affected both by the primary structure and the nature of the carbohydrate of the Fc. These results suggest that the antigen selection events which lead to the induction and production of IgG RF are likely to be different from those that induce IgM RF production.
9010058 Incidence of psoriatic arthritis in Finland. 1996 Dec Patients with psoriasis have an increased incidence of arthritis. Information on the incidence of psoriatic arthritis (PsA) is sparse. The present study covered those subjects who were entitled under the nationwide sickness insurance scheme to receive specially reimbursed medication for PsA in 5/21 central hospital districts in Finland (population basis approximately 1 million adults) in 1990. A total of 65 incident cases satisfied the concept of PsA. The annual incidence of PsA was 6/100,000 of the adult population (> or = 16 yr of age). The mean age at diagnosis was 46.8 yr. The peak incidence occurred in the 45-54 yr age group. The male to female ratio was 1.3:1. The incidence rate in the present study is in agreement with the sparse former figures, but age-specific incidence figures which have not been published earlier are also presented.