Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7706496 | Detection and expression of a cDNA clone that encodes a polypeptide containing two inhibit | 1995 Apr | RA is the most frequent and most destructive inflammatory arthropathy. Rheumatoid factors, in spite of their lack of disease specificity, are important serological markers for RA and appear important in its immunopathogenesis as well. In search of more disease-specific autoimmune systems, we have screened a human placenta lambda gt11 cDNA expression library using selected sera from patients with classical erosive RA. We have identified one clone (RA-1) that is recognized by three of five screening sera. The 950-bp insert shows a complete nucleotide sequence homology to the cDNA encoding the two COOH-terminal domains of calpastatin. The deduced open reading frame of the RA-1 cDNA predicts a 284-amino acid protein, with a calculated mol wt of 35.9 kD. Calpastatin is the natural inhibitor of calpains, which are members of the cysteine proteinases recently implicated in joint destruction in rheumatic diseases. The two domains encoded by the RA-1 clone each contain the structural features associated with the inhibitory activity of human calpastatin. By Western blotting, 45.5% or 21/44 RA sera specifically recognized both the fusion and the cleaved recombinant protein. This is in contrast to 4.7% (2/43) in nonrheumatoid sera and 0/10 in normal sera. Anticalpastatin autoantibodies could represent a disease-associated marker in chronic erosive arthritis of the rheumatoid type and could hypothetically play a dual pathogenic role, directly via an immune interference and indirectly through an immune complex mechanism. | |
| 7514412 | "Homozygosity" for the HLA-DR shared epitope contributes the highest risk for rheumatoid a | 1994 May | OBJECTIVE: To assess the contribution of HLA-DRB1 alleles in determining rheumatoid arthritis (RA) concordance in monozygotic twins. METHODS: Ninety-one monozygotic twins pairs in which at least 1 twin was affected were typed for HLA-DRB1 using both serologic methods and polymerase chain reaction amplification with sequence-specific oligonucleotide hybridization. The role of DR4 and of the shared epitope in disease concordance was investigated. Relative risks (RR) with 95% confidence intervals were determined. RESULTS: Increased concordance for RA was observed in both DR4 positive and shared epitope positive pairs (RR 3.4 and 3.7, respectively). A 5-fold risk for RA concordance was seen in twins who were "homozygous" for the shared epitope, compared with those negative for the shared epitope. CONCLUSION: In the absence of the shared epitope, RA concordance in monozygotic twins is rare. In contrast, "homozygosity" for the shared epitope is the most important factor in determining RA concordance. | |
| 8247520 | [Generalized secondary amyloidosis in rheumatoid arthritis]. | 1993 Nov 21 | Generalized (systemic) secondary amyloidosis was a post mortem finding recorded in 28 patients (25.2%) by amyloid specific Congored staining according to Romhányi, from 111 randomized autopsy cases with rheumatoid arthritis. Amyloidosis was present most frequently in the gastro-intestinal tract, the heart, kidney, thyroid gland, spleen and in the suprarenal glands. The quantity of amyloid deposits is usually the highest in the organs that are most frequently have deposits. The amyloidosis is a progressive cumulative process. The conclusion is that the organs where there are frequently high quantities of amyloid is where the deposits begin and where there are infrequently any deposits or low quantities is where the deposits develop later. Biopsy of the most frequently involved organs are suggested for early diagnosis of amyloidosis. Comparing the laboratory parameters (at the last hospitalisation), the amyloidotic patients were anaemic, with low haemoglobin level (p < 0.05), the renal function significantly decreased, the carbamid (p < 0.001), and kreatinin level high (p < 0.05), with frequent proteinuria (p < 0.0001). | |
| 8624622 | Secondary amyloidosis in patients with rheumatoid arthritis: diagnostic and prognostic val | 1996 Jan | Upper gastrointestinal endoscopy was performed in patients with rheumatoid arthritis (RA) during the period 1989-1991, and biopsy specimens were obtained from the stomach and from the duodenum for examining amyloid deposits. Among 407 patients, gastrointestinal amyloidosis was confirmed in 54 (13.3%). Twenty-two patients were regarded as having slight amyloid deposits, while 32 patients were categorized as having marked amyloid deposits. The incidence of clinical manifestations suggestive of systemic amyloidosis was more frequent in the marked deposits group than in the slight deposits group (47% vs 14%, P<0.05). Among the patients who died of manifestations associated with amyloidosis, the survival period following endoscopy was shorter in the marked deposits group than in the slight deposits group. These findings suggest that gastroduodenal biopsies may be useful for diagnosing secondary amyloidosis and that the degree of amyloid deposits seems to be correlated with the clinical manifestations of RA. | |
| 1435478 | Successful treatment of disseminated strongyloidiasis. | 1992 Sep 7 | OBJECTIVE: To report the successful treatment of Strongyloides stercoralis hyperinfection, which is usually lethal but in this case was diagnosed in its early stages. CLINICAL FEATURES: A 44-year-old woman, who had spent much of her life in Fiji and India, was treated with a high dose of prednisolone for rheumatoid arthritis complicated by gold lung. The onset of abdominal symptoms, an exacerbation of respiratory symptoms, and a persistent high eosinophil count and serum IgE level, led to the detection of numerous Strongyloides larvae in her faeces and sputum. INTERVENTION AND OUTCOME: She was treated with thiabendazole for five days, then mebendazole for one month, and the dose of prednisolone was reduced. Clinical symptoms and signs improved within days and after one week parasites could not be found in her faeces. After six months, enzyme-linked immunosorbent assay for Strongyloides infection gave a reading which was 40% of the initial level but still in the positive range. CONCLUSION: Steroid therapy in individuals with chronic, subclinical strongyloidiasis predisposes to the insidious development of hyperinfection syndrome, which has a high mortality rate. If detected early, this complication can be treated effectively. It can be prevented by actively seeking Strongyloides infection, by faecal microscopy and culture techniques and by serological tests, in high-risk individuals, such as immigrants from endemic areas. | |
| 9031118 | Humoral immune abnormalities in T-cell large granular lymphocyte leukemia. | 1996 Oct | The prevalence of humoral immune dysfunction has not been defined in a large series of patients with T-cell large granular lymphocyte leukemia (T-LGL) confirmed to be clonal by T-cell receptor analysis. Therefore we evaluated the presence of multiple autoantibodies in 27 patients with this disease. Humoral immune abnormalities included: rheumatoid factor (RF) (15/27 patients), antinuclear antibody (ANA) (13/27 patients), polyclonal hypergammaglobulinemia (15/24 patients), elevated serum immunoglobulins (17/26 patients), immune complex formation (18/25 patients), elevated beta-2 microglobulin (13/18 patients) and neutrophil-reactive IgG (18/20 patients). Disease manifestations in these patients were due to complications of cytopenia or autoimmune abnormalities. Infection was a common finding (21/27 patients) and likely reflected their neutropenia. Rheumatoid arthritis (11/27 patients), anemia (12/27 patients) and thrombocytopenia (10/27 patients) were less common but still frequently observed. This study demonstrates the presence of multiple autoantibodies in a large series of patients with documented clonal T-LGL proliferations. | |
| 8218786 | [Focal and segmentary necrotizing glomerulonephritis in rheumatoid arthritis. Description | 1993 Aug | Two patients diagnosed of seropositive Rheumatoid Arthritis, developed severe renal failure associated in one case to alveolar hemorrhage. The renal histological study showed in both patients Focal and Segmentary Necrotizing Glomerulonephritis, with extracapillary proliferation. There were no evidences of concomitant diseases or nephrotoxic pharmacological therapy in the two patients. The first patient had a positive response to the corticosteroid and immunosuppressive therapy, whereas the second patient developed an irreversible renal failure. We think that this complication, although extremely rare, must be taken into account in all patients with Rheumatoid Arthritis presenting a quick and sudden impairment of his renal function. | |
| 1520070 | [A study of opioid peptides in synovial fluid and synovial tissue in patients with rheumat | 1992 May | Authors have often experienced that psychological stress influences rheumatoid arthritis (RA). In addition, recent reports show a modulatory role for neuropeptide such as substance P in arthritis. These findings prompted us to study endogenous opioid peptides in RA, which are found mainly in the brain and have an effect on the central nervous system. We examined methionine-enkephalin (Met-enk), leucine-enkephalin (Leu-enk) and beta-endorphin (beta-end) in opioid peptides. We measured these peptides in plasma and synovial fluid samples obtained from 28 knees of 24 RA patients and the quantity in the synovial tissue of 13 knees. We also measured plasma and synovial fluid samples from patients with osteoarthritis of the knee and plasma samples from healthy candidates. Leu-enk and beta-end levels in synovial fluid were significantly higher than plasma levels only in RA. Larger quantity of Leu-end and beta-end were contained apparently in the synovial tissue than Met-enk. The synovial tissue with proliferative change tends to contain larger quantity of opioid peptides. These results indicate that the synovial tissue produces or secretes Leu-enk and beta-end and that opioid peptides are related to the degree of inflammation in RA. | |
| 8088064 | Detection of stromelysin in synovial fluid and serum from patients with rheumatoid arthrit | 1994 Jun | Stromelysin levels were measured using a one-step sandwich immunoassay in synovial fluid (SF) obtained from 31 patients with rheumatoid arthritis (RA) (31 samples) and 13 patients with osteoarthritis (OA) (13 samples) and in serum from 81 patients with RA (106 samples), 12 with OA (14 samples), 12 with gouty arthritis (gout) (14 samples), and 8 with osteoporosis (OP) (14 samples) to identify differences in the levels in these diseases as well as correlations with clinical parameters in RA. SF stromelysin levels were significantly higher in RA than in OA, and rose with increasing joint destruction in the former. No significant correlations were found between the SF stromelysin level in RA and various clinical parameters, except for the volume of SF which showed a correlation. Serum levels of stromelysin were highest in RA, gout, OA, and osteoporosis in decreasing order, and in RA were correlated with the Steinbrocker Stage. A significant correlation was also found between the serum stromelysin level and number of swollen joints, and correlations with the Lansbury index, ESR, CRP, WBC and Plt. The stromelysin level in SF was thought to be a useful parameter of local joint involvement and that in serum of the severity of systemic joint inflammation. | |
| 8578315 | Botanical lipids: effects on inflammation, immune responses, and rheumatoid arthritis. | 1995 Oct | OBJECTIVE: This review discusses the rationale and experimental data that led to clinical trials of certain botanical lipids, mainly gammalinolenic acid (GLA), for the treatment of rheumatoid arthritis (RA). DATA SOURCES: Pertinent articles and reviews, and a bibliographic database in English using the following indexing terms: rheumatoid arthritis, fatty acids, gammalinolenic acid, lymphocytes, and monocytes, were used. STUDY SELECTION: All clinical trials in which GLA was used to treat arthritis are included in this review. Data from appropriately peer reviewed in vitro and animal experiments evaluating the effects of botanical lipids as regulators of cell activation and immune responses are also reviewed. DATA SYNTHESIS: GLA treatment is associated with clinical improvement in patients with RA, as evaluated by duration of morning stiffness, joint pain and swelling, and ability to reduce other medications. However, studies vary in terms of duration, GLA dose, whether or not they were placebo controlled, and, if so, what placebo was used, criteria for evaluation, and use of concomitant medication. Studies done in vitro generally indicated that GLA reduces lymphocyte activation and production of mediators of inflammation. CONCLUSIONS: A small number of studies suggest that GLA is effective treatment for RA patients. Further controlled studies of its use in RA seem warranted. | |
| 8453797 | The effect of bed rest and intra-articular steroids on the acute phase response in rheumat | 1993 Jan | The impact of therapeutic interventions on the disease process in patients with rheumatoid arthritis (RA) is complex. The effect on the acute phase response was studied in 25 in-patients on imposed bed rest, who were randomised to treatment with (n = 12) or without (n = 13) intra-articular steroids. C-reactive protein (CRP), ESR and IgA alpha-1 antitrypsin complex levels were measured on admission and on days 3 and 5. Levels at onset were not different between groups. At day 3 and day 5, a significant (p < 0.001) fall in CRP was seen only in the intra-articular steroid group. Other cytokine and disease parameter measures did not alter during the study period (although IL-6 and CRP correlated at onset in all 25 patients). The mean duration of the hospital stay was longer for the patients treated with bed rest only. Thus, bed rest when combined with intra-articular steroids produced a rapid systemic effect, while bed-rest alone did not have an effect on the acute phase response over this short time scale. | |
| 8778985 | Mortality in rheumatoid arthritis: do age and gender make a difference? | 1996 Apr | Rheumatoid arthritis (RA) is a significant cause of morbidity and mortality in both sexes. The extent to which age and gender are risk factors for increased mortality in RA, however, is still not clear. A review of existing literature on the effect of gender and age on mortality was performed. Twenty-five articles were identified from the world literature over the past decade. Ten articles representative of the existing literature in this field were analyzed in detail. Articles chosen as representative were characterized by peer-reviewed publication, large sample size, and geographic diversity of patient populations. One detailed analysis of prior literature also was included. The results failed to show a clear association between gender, age, and mortality in RA. Retrospective analyses of death certificates suggest an increased mortality among elderly women with RA. Longitudinal studies, however, suggest that both increasing age and male sex portend a worse prognosis in RA. A better understanding of mortality risk factors in RA, particularly with respect to age and gender, would require large randomized prospective trials conducted over long periods. | |
| 7570204 | [The relationship between genotypes of HLA-DRB1 alleles and progression of bony destructio | 1995 Jun | The relationship between genotypes of HLA-DRB 1 alleles and the progression of bone destruction of RA patients was assessed. The genotypes of the HLA-DRB 1 alleles were determined in 329 Japanese patients with seropositive RNA by polymerase chain reaction and allele-specific oligonucleotide probe techniques. We regarded HLA-DRB 1* 0101, 0401, 0404, 0405, 1001 and 1402 as susceptible alleles of RA and classified the patients into three groups. The s/s group consisted of those with susceptible factors in both of the HLA-DRB 1 alleles. The s/n group was made up of those having one susceptible factor and one non-susceptible factor. The n/n group consisted of those possessing two non-susceptible factors. The grading of radiographic change that was evaluated by Larsen's criteria compared with the genotyped results. In the result, the median years taken to development to grade III, IV and V were significantly shorter in the s/s groups compared with that in the s/n and n/n groups. Thus, genotyping of HLA-DRB 1 can be a useful prognostic market in the progression of bone destruction of RA. | |
| 8744695 | Influence of gold salts treatment on the serum concentration of IL-1 and IL-2 in patients | 1995 | Eighteen subjects (2 males, 16 females) with rheumatoid arthritis were treated with gold salts for 6 months. The statistically significant decrease of IL-1 and IL-2 levels during the treatment was observed. The mean serum concentrations of IL-1 and IL-2 decreased from 41.0 +/- 11.5 to 28.6 +/- 7.3 (p < 0.001) and 98.3 +/- 57.6 to 29.3 +/- 20.5 fmol/ml (p < 0.001), respectively. This decrease was accompanied by a decline of serum concentration of acute phase proteins and immunoglobulins. These results can explain a strong anti-inflammatory action of gold salts in patients with rheumatoid arthritis. | |
| 8231667 | Magnetic resonance methods for measurement of disease progression in rheumatoid arthritis. | 1993 | Magnetic resonance imaging methods are described for measurement of disease activity in knee in rheumatoid arthritis patients. Measurements of cartilage thickness, joint effusion volume, and pannus volume have been made. The latter measurement relies on synthetic fractional enhancement images of the response to gadopentetate dimeglumine. | |
| 8208996 | [Morphological pictures of renal biopsy specimens in glomerulopathies related to rheumatoi | 1994 | The authors reevaluated 21 renal biopsy specimens from patients with rheumatoid arthritis (RA) and clinical symptoms of glomerulopathy. The patients were divided into three groups: in the I group they were treated with nonsteroid antiinflammatory drugs, in the II one with gold and in the III group with D-penicillamine. Pathomorphological study based on light microscopy, immunohistochemistry and electron microscopy showed that forms of primary renal involvement (group I) and secondary renal involvement (group II and III) in patients with rheumatoid arthritis were very similar to the types of glomerulonephritis not related to RA. The authors pointed out, that in the most cases immunohistochemistry revealed immunoglobulins (IgG,IgA,IgM,C3) and electron microscopy investigations showed deposits in various parts of the glomeruli. This observations support opinions, that immune complex mechanism takes a great role in pathogenesis of glomerulopathy in RA. | |
| 8598699 | Randomised placebo-controlled study of stopping second-line drugs in rheumatoid arthritis. | 1996 Feb 10 | BACKGROUND: A favourable benefit/risk ratio for treatment of rheumatoid arthritis (RA) with second-line drugs has been established only in short-term studies. The present investigation addresses the question of whether RA patients with a good response to long-term treatment with second-line drugs benefit from continuation of such treatment. METHODS: A 52-week randomised double-blind placebo-controlled multicentre study was conducted to assess the effect of stopping second-line therapy in 285 RA patients with a good long-term therapeutic response. The patients either continued the second-line drug (n = 142) or received a placebo (n = 143). The endpoint was a flare, defined as recurrence of synovitis. FINDINGS: At entry into the study median duration of second-line drug therapy was 5 years (range 2-33). At 52 weeks the cumulative incidence of a flare was 38% for the placebo group and 22% for the continued therapy group (p = 0.002). The risk of a flare was 2.0 times higher for patients receiving placebo than for those continuing the second-line drug (95% CI 1.27 to 3.17). The same trend was found for each second-line drug separately, with the exception of d-penicillamine. Side-effects that necessitated dose reduction or discontinuation occurred in 2 patients in each group. INTERPRETATION: Second-line drugs continue to be effective in RA patients who have responded well to initial treatment. | |
| 8792514 | Muscle involvement in rheumatoid arthritis: clinicopathological study of 21 symptomatic ca | 1996 Jun | The aim of the current study was to analyze the frequency and characteristics of symptomatic myopathies occurring in rheumatoid arthritis (RA) patients, to correlate these findings with clinical data, and to evaluate their therapeutic implications. All RA patients from a cohort of 350 RA patients from a single institution who developed muscular symptomatology during an 8-year period were included in the study (n = 21). Clinical and laboratory data and electromyographic results were recorded in all cases, and an open muscle biopsy was performed. Weakness and muscle atrophy were the most common symptoms. Serum creatine kinase was increased in 8 cases (38%). Histopathologic study showed type 2 atrophy in 12 cases. In 13 cases, a treatable disease was diagnosed: dermatomyositis (n = 2), d-penicillamine-related dermatomyositis (n = 2), polymyositis (n = 1), muscular mononuclear cell infiltration (n = 3), polyarteritis nodosa (n = 1), glucocorticoid myopathy (n = 3), and toxic chloroquine myopathy (n = 1). In all but 1 patient, muscular clinical response to new therapy and/or drug withdrawal was satisfactory. Although symptomatic muscular involvement in RA is low (6% in the current series), we have found that nearly two thirds of cases were caused by potentially treatable conditions, mainly myositis or toxic myopathies. | |
| 8596140 | HLA-DPB1 polymorphism in patients with rheumatoid arthritis in Taiwan. | 1995 Nov | OBJECTIVE: To investigate the role of HLA-DP alleles in the pathogenesis of rheumatoid arthritis (RA). METHODS: HLA-DPB1 alleles were studied in 144 patients with RA and 144 healthy controls using the polymerase chain reaction/sequence specific oligonucleotide probe method. RESULTS: HLA-DPB1*0510 was the the most common allele in patients with RA and healthy controls in Taiwan. There was no significant difference in frequencies of HLA-DPB1 alleles between patients and controls. The HLA-DPB1 alleles were not associated with seropositivity for rheumatoid factor, extraarticular involvement, or bone erosion in patients. There was also no significant difference in frequencies of HLA-DPB1 alleles among DR4-positive and DR4-negative patients and controls. CONCLUSION: There was no significant difference in the prevalences of HLA-DPB1 alleles between Taiwanese patients with RA and healthy controls. HLA-DPB1 alleles were not related to the clinical manifestations of patients with RA in Taiwan. | |
| 1588750 | [Cardiac and pulmonary manifestations in rheumatoid arthritis]. | 1992 Mar | Pericarditis may be the most common cardiac manifestation in RA patients and the incidence in autopsy cases is more than 30%. Pericardial effusion shows low sugar and complement level and high level of LDH and gamma-globulin. The administration of corticosteroids has been successfully used in the treatment of rheumatoid pericarditis. The pulmonary involvement in RA include pleuritis, nodules and interstitial lung disease. Interstitial lung disease in RA patients appears to run a continuum from mild pneumonitis to severe pulmonary fibrosis and occasionally it include bronchiolitis obliterans organizing pneumonia (BOOP) which is sensitive to corticosteroid therapy. Although open lung biopsy is the definitive procedure for proving the diagnosis of interstitial lung disease, open lung is now being complemented or replaced by transbronchial lung biopsy and bronchoalveolar lavage (BAL). Corticosteroids will be effective to BOOP definitely and in general usual interstitial pneumonia (UIP) is resistant to treatment. In addition to the primary pulmonary manifestations of RA, anti-rheumatic drug reactions in the lung may be associated. |