Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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3257870 | Interleukin-1 activates phospholipase A2 in human synovial cells. | 1988 Jan | Interleukin-1 (IL-1) treatment of synovial cells from rheumatoid arthritis and osteoarthritis patients resulted in a dose-dependent secretion of phospholipase A2 (PLA2). IL-1 also stimulated prostaglandin E2 and plasminogen activator synthesis, in parallel with PLA2 activation; all 3 were detectable within 6 hours of IL-1 treatment and peaked by 24 hours. Synovial cell PLA2 required calcium (5 mM) and a neutral pH (7.5) for maximal activity and appears similar to the PLA2 in synovial fluid, which has been described previously. We conclude that PLA2 can be induced by IL-1, and its secretion may contribute significantly to the inflammatory actions of IL-1. | |
2059230 | Association of HLA-DR4 with a more progressive disease course in patients with rheumatoid | 1991 Jul | The association between HLA-DR antigens and rheumatoid arthritis (RA) was investigated in a well-characterized cohort of RA patients who were followed from the beginning of the disease (mean followup 6 years). The frequencies of HLA-DR antigens in patients with possible or probable RA (n = 49) were similar to those in controls. In patients with definite RA (n = 134), the frequencies of DR1, DR4, and DRw53 were increased, whereas the frequencies of DR2, DR3, DRw6, DRw13, and DRw52 were decreased, compared with controls. Comparison of HLA-DR frequencies in patients with definite RA subclassified according to the severity of the disease at the end of the followup period revealed a difference only in the frequency of DR4, which was increased in patients with progressive RA (59.2%) compared with those who had mild RA (34.8%). Further analysis showed that, compared with DR4-negative RA patients, DR4-positive patients had more swollen joints, higher scores on the Ritchie articular index, the Health Assessment Questionnaire, and the Steinbrocker functional classification, more radiologic abnormalities, and more use of second-line drugs. Also, the rate of progression of radiologic abnormalities, functional classification, and use of second-line drugs was higher in DR4-positive patients. We conclude that DR4 is associated with a more severe disease course, and is a prognostic marker in early RA. | |
3715618 | Medullary compression in rheumatoid atlanto-axial subluxation evaluated by computerized to | 1986 Apr | CT examination of rheumatoid dislocation in the C1-C2 region was performed in 20 patients with advanced disease. The patients were classified in three grades according to the degree of medullary compression caused by the odontoid process in the extended position of the neck. Five patients showed no dural or medullary compression (grade 1), nine dural compression (grade 2), and six medullary compression (grade 3). CT grading was found to correlate best with long tract symptoms. These were present in 4/6 grade 3 and 0/5 grade 1 patients, while 3/9 grade 2 patients had long tract symptoms. Tissue attenuation values over the anterior atlanto-axial joint indicated interposing firm connective tissue in patients showing no reduction of the subluxation on extension of the neck. | |
2491472 | [Plasma and intraerythrocytic zinc in rheumatoid arthritis and ankylosing spondylitis]. | 1989 Dec | The levels of plasmatic and intraerythrocyte zinc in our control group did not show differences in accordance with age or sex. Patients affected by rheumatoid arthritis showed a decrease of plasmatic levels of zinc and an increase of intraerythrocyte zinc level. The patients with ankylosing spondylitis did not show significant variations of zinc levels, even though the patient with increased SR after the first hour (25 mm) showed lower plasmatic zinc with statistical significance. Finally, patients with rheumatoid arthritis in treatment with NSAID, low dose of steroids, gold salts, D-penicilamin, did not show differences compared to the total group of patients with this disease. | |
2261697 | Evaluation of a simple method for the measurement of cytidine deaminase in serum and compa | 1990 Nov 15 | This study was designed to evaluate a cytidine deaminase (CD) assay modified to allow results to be achieved within one working day. Inter-batch variation for samples of mean (SD) CD activity, 10.2 (1.0) units, 17.5 (1.2) units and 31.7 (1.7) units were, 9.8%, 6.9% and 5.4% respectively (n = 26). The reference range (3.2-13.2 U) was similar in males and females and was independent of age. There was close correlation with a reference method (r = 0.96). The mean difference between methods was 2.7 U and the limits of agreement were -1.7 to 7.1 U. The results indicate that the short assay technique can produce results that are sufficiently accurate and precise to be clinically useful. | |
2075374 | Interleukin 1 beta in synovial fluid is related to local disease activity in rheumatoid ar | 1990 | Interleukin 1 beta (IL-1 beta) is a polypeptide with pro-inflammatory and immunopotentiating effects in vivo and in vitro. With relevance to rheumatoid arthritis (RA) IL-1 augments release of prostanoids, proteinases and oxygen metabolites and is a potent inducer of bone and cartilage resorption. Although high levels of IL-1 have been found in rheumatoid synovial fluids, intra-individual variation in IL-1 production has made it difficult to correlate these levels with disease activity. To overcome this problem we have studied patients with symmetrical and asymmetrical knee joint inflammation. Local disease activity was documented using Ritchie score and joint circumference; IL-1 beta levels were quantitated in synovial fluid by ELISA. In patients with symmetrical joint involvement almost identical levels of IL-1 beta were detected in the right and left knee joints. In contrast, in patients exhibiting asymmetrical knee joint involvement, IL-1 beta levels in the inflamed joints were significantly higher than in the contralateral joints. The study provides further evidence for the role of IL-1 in the pathogenesis of rheumatoid inflammation. | |
3492039 | Rheumatoid arthritis with pleural effusion includes a subgroup with autoimmune features an | 1986 | Twenty-eight patients with rheumatoid pleural effusion were investigated to examine the frequency of HLA antigens as compared with 56 rheumatoid arthritis (RA) patients without this intrathoracic manifestation of RA and with 283 healthy controls. HLA-B8 was strongly associated with the presence of pleural effusion (PE) in RA patients. A high prevalence (71%) of B8/Dw3 was found among male RA patients of the PE group in whom the joint disease had begun at an age over 50 years and who also had besides pleuritis other intrathoracic manifestations of RA associated with high rheumatoid factor titres and low complement (C4) levels in sera. Actually, the HLA-B8 association was not seen in the rest of the PE group. The finding may be related to the heterogeneity of RA, a male subgroup of the disease being characterized by multiple intrathoracic manifestations and genetically associated with the large group of autoimmune disorders, such as SLE, characterized by high prevalences of HLA-B8 and D(R)3. | |
3616376 | [Changes in the respiratory function in Gougerot-Sjögren syndrome]. | 1987 | Tests for lung function assessment were performed in 36 subjects (34 women, 2 men; mean age 56 +/- 2.2 years) presenting with Sjögren's syndrome of 8.4 +/- 1.0 years duration. The tests used in the study were: spirography with measurement of residual volume, flow volume curve, total dynamic resistances, diffusing capacity of the lung (steady state and breath hold methods), estimation of alveolar ventilation and, in some subjects, dynamic lung compliance. Sjögren's syndrome was assessed by anatomo pathological methods and divided into primary (n = 9) and secondary (n = 27). Secondary Sjögren's syndrome (SGS II) was associated mainly with a connective tissue disease (rheumatoid arthritis in 23 cases). The results of lung function tests showed distal airway obstruction associated with a decrease in lung diffusing capacity due to functional disturbance of the alveolar capillary membrane. Moreover, the greater alteration of lung function observed in SGS II could be explained by: a direct correlation between duration of SGS and alteration of lung function, and an alteration of the parietal ventilatory mechanics, at least in subjects with rheumatoid arthritis. | |
1971455 | [Tiopronin, an example of hydrosulphonated derivatives used in the treatment of rheumatoid | 1990 Apr 10 | Fifteen patients with rheumatoid arthritis were treated with tiopronine, and an immunological check-up carried out before the onset and after a two-month treatment. The latex test titres decreased, and there was a significant fall in the levels of IgA-containing circulating immune complexes, in parallel with a depletion of plasma complement breakdown products. Patients displayed a decrease in CD8+T cells and in CD4+Leu 8-T cells and a high proportion of activated T lymphocytes. This returned to normal after treatment. Treatment with TP led also to a reduction of adherence and chemotaxis of polymorphonuclear cells. | |
3393843 | [Rheumatoid polyarthritis. Misleading aspects and its doubles]. | 1988 Apr 30 | The diagnosis of rheumatoid arthritis is easy for typical forms, but is difficult in certain cases. This is especially true at the onset of the disease. In fact, 10 to 15 p. cent of rheumatoid arthritis cases present onsets which are more or less deceptive, either in their mode, or localization. Until now, no valid assistance could be expected from the pathology, serology or even immunogenetics and molecular biology. In forms seen in their active phase, there are a number of diseases, of various causes, which may simulate rheumatoid polyarthritis. It is absolutely necessary to recognize them in order not to embark on an erroneous therapeutic approach. | |
2016609 | Early failure of silicone radial head implants in the rheumatoid elbow. A complication of | 1991 Mar | Three cases of early recurrent synovitis of the rheumatoid elbow following silicone radial head implant arthroplasty are presented. All three patients underwent synovectomy with silicone radial head implant for pain and loss of function due to rheumatoid synovitis. All three implants failed within 4-9 months after surgery. This failure was associated with radiographic medial joint space widening. At reexploration, recurrent synovitis with hemosiderin pigmentation was noted. Patterns of prosthetic failure included fracture, fraying, and compressive deformation or rotary wear ("motar and pestle") of the silicone radial head; a prosthetic stem fracture was also present. Histologic examination of the synovium revealed evidence of silicone-induced synovitis; particulate, refractile silicone debris was associated with inflammatory and foreign body giant cells. The presence of rheumatoid destruction of the joint surface may have accelerated this process and may be a relative contraindication to silicone radial head implant arthroplasty. | |
2479344 | Human epidermal growth factor for the stratification of synovial lining layer and neovascu | 1989 Oct | Immunohistochemical study showed selective localisation of human epidermal growth factor (hEGF) to the synovial lining layer. Although the synovial lining layer of the rheumatoid, osteoarthritic, and traumatic joints was hEGF positive, hEGF staining was especially dense at the rheumatoid synovial lining layer; the staining increasing linearly according to the degree of stratification of the lining layer (r = 1). Human epidermal growth factor was ultrastructurally localised to cytoplasm, especially to rough endoplasmic reticulum, of the synovial lining fibroblast-like (type B) cell. Only the cell surface of macrophage-like (type A) cells was hEGF positive. When different histological variables were compared with each other a positive correlation was found between hEGF staining of the synovial lining layer and the degree of neovascularisation of rheumatoid synovium (r = 0.72). Although some lymphocytes were weakly hEGF positive, neovascularisation did not correlate with the extent of lymphocyte infiltration or of hEGF staining of lymphocytes. Lymphocyte infiltration or hEGF staining of lymphocytes did not correlate with hEGF staining of the synovial lining layer, whereas the lymphocyte infiltration correlated positively with the extent of perivascular accumulation of lymphocytes (r = 0.89). These findings suggest that (a) hEGF is synthesised by and secreted through endoplasmic reticulum and Golgi apparatus from the synovial lining type B cell; (b) hEGF is at least partially responsible for the pathogenesis of stratification of the rheumatoid synovial lining layer, and perhaps of neovascularisation of the rheumatoid synovium, whereas it is not responsible for lymphocyte accumulation to the rheumatoid synovium. | |
3188864 | Remodeling of the tibial plateau after knee replacement. CT bone densitometry. | 1988 Oct | We measured the changes of bone density by computed tomography of the proximal tibia after total knee replacement in 18 patients, 9 with arthrosis and 9 with rheumatoid arthritis. All the patients had good results after 1 and 2 years. There were no significant radiolucencies at the cement-bone interface. At the early postoperative measurements, we found abnormal mediolateral distributions of density, closely related to the preoperative tibiofemoral angle (r = -0.67). This distribution was within normal limits after 3 months in knees with preoperative valgus and after 2 years in knees with preoperative varus. The mean tibial density did not differ between patients with arthrosis and rheumatoid arthritis at the early postoperative examination, but the density in rheumatoid patients decreased by one third during the 2-year period. Although the overall change after knee replacement was loss of density, the preoperatively less loaded condyles had a slight tendency towards increasing density with time, a response that was considerable in some cases. | |
2047554 | [Rheumatoid arthritis and chronic granular T-cell lymphocytosis with neutropenia. A clinic | 1991 Mar | 103 cases of rheumatoid arthritis who had been diagnosed between 1984 and 1985 have retrospectively been analyzed, in order to identify those patients who had presented with associated neutropenia and in whom it was thus possible to suggest a presumptive diagnosis of either Felty's syndrome or chronic granulated lymphocytosis with neutropenia. Four patients (3.8%) satisfied the clinical criteria for the latter diagnosis while only one had typical Felty's syndrome. They were again studied using blood counts, microscopy of bone marrow and surface antigen analysis of mononuclear cells and the above mentioned diagnoses were confirmed. Though clinically indistinguishable, these two conditions are clearly distinct on both hematologic and immunological grounds. The four patients with rheumatoid arthritis and chronic granulated T cell lymphocytosis with neutropenia represent 36.3 per cent of our institution's patients with chronic granulated T cell lymphocytosis of undetermined significance. Caution should be used in the treatment of rheumatoid arthritis of the patients with associated granular lymphocyte proliferation, considering the possible adverse effects that drugs such as gold salts, penicillamine, cyclosporine and methotrexate may exert not only on the immunological system but also on granulocytopoiesis. | |
3801069 | Modulation of spontaneous immunoglobulin production by natural killer cells in rheumatoid | 1986 Dec | Synovial fluid (SF) mononuclear cells obtained from patients with rheumatoid arthritis (RA) spontaneously produce large amounts of immunoglobulin. In the rheumatoid joint, natural killer (NK) cell activity is reduced in comparison with that in the peripheral blood (PB). We examined the ability of SF NK cells to modulate the spontaneous production of Ig in RA SF, and we contrasted this with the activity in PB from RA patients and from normal subjects. We found that the spontaneous production of IgG was greater in RA SF than in RA or normal PB. The baseline NK activity was significantly lower in RA SF than in RA or normal PB (P less than 0.005). Incubation with anti-Leu-11b and complement reduced NK activity in PB, but not in SF, and it significantly (P less than or equal to 0.021) increased IgG production in both RA SF and RA PB. Lysis of NK cells in this manner also resulted in a significant increase (P less than 0.02) in IgM production in RA SF. These results suggest that NK cells with a Leu-11b phenotype down-regulate the ongoing synthesis of IgG and IgM in the rheumatoid joint. | |
2269799 | Boutonniere rheumatoid thumb deformity. | 1990 Nov | The boutonniere deformity is the most common rheumatoid thumb deformity. It can be classified into early, moderate, and advanced types, depending on whether the deformity is passively correctable. Fifty-three patients with 74 procedures form the basis of these recommendations. The early type treated with metacarpophalangeal joint synovectomy and extensor pollicis longus rerouting have a high recurrence rate of 64%. Metacarpophalangeal joint fusion is the procedure of choice for the moderate type with isolated metacarpophalangeal joint involvement. Metacarpophalangeal joint arthroplasty is best suited for the low-demand, older patients with borderline proximal and distal joints. Interphalangeal joint releases done with metacarpophalangeal joint fusions have a high recurrence rate and are not recommended. In advanced cases metacarpophalangeal joint arthroplasty and interphalangeal joint fusion is our procedure of choice. | |
3592799 | Relation between bone erosions and rheumatoid factor isotypes. | 1987 May | Total rheumatoid factor (RF) activity and individual RF isotypes were measured in 62 patients with rheumatic diseases. Retrospective analysis of available x rays showed an association between IgA RF and the occurrence of periarticular bone erosions in hands. In contrast, IgG RF and IgM RF did not show any significant association with erosions. Furthermore, a close correlation was observed between the RF isotype levels in simultaneously drawn serum and synovial fluid samples. The possible significance of IgA RF in the pathogenesis of bone erosions is discussed. | |
2634884 | [Association of immunomodulators and HLA antigens in rheumatoid arthritis]. | 1989 Oct | We studied the association between HLA antigens and clinical response to immunomodulators or the toxic effects of immunomodulators in 191 patients with rheumatoid arthritis (RA). All patients received nonsteroidal anti-inflammatory drugs. Fifty-seven patients were treated with auranofin, 61 patients with penicillamine and 45 patients with lobenzarit. We found that HLA-Cw 1 is significantly (p less than 0.05) associated with a substantial clinical response to auranofin in RA patients (65% vs 33% of Cw 1-negative patients). We observed that HLA-DR 4 is a risk factor for the occurrence of toxic reactions to penicillamine (45% vs 21% of DR 4-negative patients: p less than 0.05) and that HLA-DRw 9 is a risk factor in the case of lobenzarit (62% vs 32% of DRw 9-negative patients: p less than 0.05). HLA-A 24-positive patients with RA experienced a low frequency of side effects from auranofin (16% vs 37% of A 24-negative patients: p less than 0.05). HLA-A 2 or Cw 7-positive patients with RA experienced a low frequency of side effects from penicillamine (12% vs 49% of A 2-negative patients: p less than 0.01, 17% vs 46% of Cw 7-negative patients: p less than 0.05). Our data demonstrated that HLA antigens are significantly associated with a clinical response to immunomodulators and the toxic effects of immunomodulators in patients with RA. | |
1972665 | Response of immunoregulatory lymphocyte subsets to methotrexate in rheumatoid arthritis. | 1990 May | In an attempt to define the immunoregulatory mechanisms operating in rheumatoid arthritis, the authors examined peripheral blood functional lymphocyte subsets in 15 patients with active rheumatoid arthritis who were not receiving remittive therapy, as well as 33 healthy controls. The percentage and absolute numbers of total T cells (CD3), T-helper/inducer cells (CD4), and T-suppressor/cytotoxic cells (CD8) did not differ among the groups, nor did the CD4:CD8 ratio or the numbers of T cells coexpressing CD4 and the activation markers Ia or IL-2R. However, rheumatoid arthritis patients did have reduced percentages and numbers of CD4+ cells coexpressing the 2H4 antigen (CD45R-naive T cells) (P less than .0003) and CD8+ cells coexpressing the Leu-15 (CD11b) marker (suppressor/effectors) (P less than .0005). Twelve patients then received oral methotrexate, 7.5 mg weekly. Most showed clinical improvement by 4 weeks and all did by 8 weeks. Although changes in the T-cell subsets were not statistically significant, several tended toward normalization. These findings may help explain the immunoregulatory defect in rheumatoid arthritis and the effectiveness of methotrexate in modifying disease activity. | |
2128475 | A three year comparative study of auranofin and gold sodium thiomalate in rheumatoid arthr | 1990 Dec | One hundred twenty-one patients with active RA were randomly assigned to receive 6 mg auranofin (AF)/day (60 patients) or 50 mg gold sodium thiomalate (GST)/week (62 patients) in a double-blind fashion. There were no intergroup differences with respect to sex, age, duration (median 2 years), stage and activity of the disease. In the case of "striking improvement" after 24 weeks a dose reduction to 50 mg GST/month or 4 mg AF/day was allowed and carried out in all GST patients and no AF patient. The serum gold levels were 5 times higher with weekly GST, they approached those of the AF group with monthly GST injections. The clinical parameters--number of swollen joints, activity index, articular index, grip strength, ESR--improved significantly in both groups, but grip strength, articular index and ESR improved more pronounced in the GST group. The X-ray progression (hands and forefeet) was significantly greater in the AF group. Forty-eight AF patients (80%) and 39 GST patients (36%) completed the first year. Thereafter the study was continued as an open study but the patients were allowed to switch from GST to AF. After the first and second year 14/7 GST patients switched to AF. The second/third year was completed by 37/22 AF pat. (62%/37%) and by 15/8 GST pat. (24%/13%). Skin reactions were more common with GST (41.9%/26.7%), diarrhoea was more common with AF (36.7%/19.4%), proteinuria occurred in 10% in both groups, leucopenia and thrombocytopenia were rare in both groups (1.7%). The withdrawal rate due to adverse events was 10%/26% in the AF/GST group during the first year (p less than 0.05) and 25%/32% over the three year period (n.s.). CONCLUSION: Both AF and GST are effective in the long-term treatment of RA, but GST is more so in radiological progression and ESR. |