Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2200356 | Agalactosyl IgG, antibodies to heat shock proteins, and acute rheumatic fever. | 1990 Jun | In rheumatoid arthritis an increased proportion of the N-linked oligosaccharides on serum IgG terminate with N-acetylglucosamine (agalactosyl IgG). It has recently been shown that group A streptococcal cell wall peptidoglycan/polysaccharide complex may be used to raise monoclonal antibodies which bind to this glycoform of IgG. Patients with rheumatoid arthritis also have increased levels of antibody to the 65 kD and 70 kD families of heat shock proteins, particularly to a bacterial (Mycobacterium bovis) homologue of heat shock protein hsp65. Streptococci must contain similar heat shock proteins. Acute rheumatic fever follows infection with group A streptococci, and these organisms might theoretically evoke antibody to heat shock proteins or changes in the levels of agalactosyl IgG, which is antigenically cross reactive with their cell walls. It is shown here that serum samples from patients with acute rheumatic fever do not differ from those from normal children by these criteria. | |
| 3111928 | Inflammation and the mechanism of action of anti-inflammatory drugs. | 1987 Aug | Inflammation is caused by release of chemicals from tissues and migrating cells. Most strongly implicated are the prostaglandins (PGs), leukotrienes (LTs), histamine, bradykinin, and, more recently, platelet-activating factor (PAF) and interleukin-1. Evidence for their involvement comes from studies with competitive antagonists for their receptors and inhibitors of their synthesis. H1 histamine antagonists are effective for hay fever and some skin allergies such as urticaria, which indicates the importance of histamine in these conditions. Symptoms of rheumatoid arthritis are alleviated by the aspirinlike anti-inflammatory drugs, which inhibit the cyclo-oxygenase enzyme and reduce synthesis of prostanoids. Corticosteroids prevent the formation of both PGs and LTs by causing the release of lipocortin, which by inhibition of phospholipase A2 reduces arachidonic acid release. They suppress the inflammation of rheumatoid arthritis and asthma. Currently, high doses of nonsedating H1 antihistamines and PAF antagonists are being tested for the treatment of allergic asthma. | |
| 2282662 | Immunoregulatory mechanisms present in the maternal circulation during pregnancy. | 1990 Apr | Systemic alterations of the maternal inflammatory and immune system occur during pregnancy. These changes alone are unlikely to be responsible for the acceptance of the fetal semiallograft. Numerous local events at the maternal-fetal interface appear to be more important. The alterations of the maternal inflammatory and immune systems are subtle enough for no significant increase of infections or malignancy to be apparent. However, 75% of women with rheumatoid arthritis are clinically improved during pregnancy. The effects of pregnancy on polymorphonuclear cells are not likely to be responsible because cell function actually appears enhanced in vivo, despite the fact that pregnancy serum is suppressive in vitro. There is no clear evidence for reduction of monocyte/macrophage function during pregnancy, either in vivo or in vitro. It is unlikely that modulation of B cell phenotype or function is responsible because no suppression is noted, either in vivo or in vitro. Selected products of B cells, immune complexes, appear to be reduced during pregnancy. In patients, the reduction in the concentration of complexes may be due to adsorption by the placenta. The importance of this reduction as a causative factor in the improvement of women with rheumatoid arthritis during pregnancy remains to be determined. Natural killer cell cytotoxicity is decreased during pregnancy. This may in part be due to the release of progesterone induced blocking factor. It is also possible that circulating factors, capable of inhibiting IL-2 release or IL-2 function in vivo, might be responsible. Natural killer cytotoxicity can be normalized by incubation with IL-2. It is unclear how the reduction of natural killer cell activity might systematically affect inflammation or immunity in vivo during pregnancy. In vivo delayed type hypersensitivity appears somewhat reduced during pregnancy. This observation appears consistent with the improvement of rheumatoid synovitis, which is also thought to be T cell mediated. T cell function, measured in vitro, generally appears normal. However, most recent studies have employed mitogens, such as PHA, which is not physiological. Subtle defects involving antigen processing or antigen presentation might be missed in this system. These observations suggest that circulating factors might be important in modulating the cell mediated immune system, in vivo, during pregnancy. While anti-HLA-DR antibodies eluted from the human placenta may be effective therapy in patients with rheumatoid arthritis, their occurrence is too infrequent to account for the improvement seen in afflicted patients.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 2573159 | [Effect of salazosulfapyridine and its metabolites on immunocompetent cells]. | 1989 Jun | Long-term administration of SASP does offer clinical benefit and has a demonstrable disease modifying effect in rheumatoid arthritis, though its mode of action remains obscure. We have studied the in vitro effects of SASP and its metabolites, that is SP, ASA, AcSP and AcASA, on the blast-formation of lymphocytes, the cytotoxic activity of NK cell, the phagocytosis and H2O2 production of monocyte and the fMLP-induced chemotaxis and superoxide anions production of PMNs. We have obtained the following results: (1) the blast-formation of lymphocytes by PHA and Protein A was significantly inhibited by SASP, but not by the metabolites; (2) the cytotoxic activity of the NK cell was inhibited by SP and AcSP, but not by SASP, ASA and AcASA; (3) on monocyte, SP, AcSP and AcASA inhibited phagocytosis, and all of drugs had no effect on the production of H2O2; (4) on PMNs, SASP, SP and ASA significantly inhibited fMLP-induced chemotaxis, and SASP and all of its metabolites significantly inhibited a release of superoxide anions by stimulation of fMLP and PMA; (5) SASP and ASA scavenged superoxide radical at the concentration comparable to clinical doses. In vivo, the above effects may be exhibited in proportion to each blood concentrations of drugs. In particular, it appears that SASP, SP and AcSP play an important role in the therapeutic efficacy in rheumatoid arthritis. | |
| 3088275 | The use of lidocaine to reduce the pain of myochrysine injections for children with juveni | 1986 Apr | Myochrysine (gold sodium thiomalate, GSTM) injections are the therapy of choice for children with refractory juvenile rheumatoid arthritis. In this single blinded study 8 children receiving GSTM were asked to rate their discomfort after a total of 185 injections of GSTM to which were added in random fashion either 0, 0.1, or 0.25 ml of 1% lidocaine. The addition of 0.1 ml of lidocaine was associated with a reduction of the mean complaint of pain on an ordinal pain score of 1-10 from 4.32 for injections containing no lidocaine to 2.54 for injections containing 0.1 ml (p less than .01). Addition of 0.25 ml of lidocaine did not provide a significant increase in pain reduction (p greater than .05). | |
| 3029375 | Elevated serum immune complex levels in Pogosta disease, an acute alphavirus infection wit | 1986 Oct | Circulating immune complexes (CIC) were studied in Pogosta disease, an acute alphavirus infection with fever, rash and arthritis. The disease is caused by a virus antigenically closely related to Sindbis virus. 75 serum specimens from 25 patients with serologically verified infection were obtained from 1-87 days after the onset. Six different CIC detection methods were used and CICs were observed in all patients at least with one test. Tests based on CIC binding onto human platelets followed the natural course of the disease and maximal values were observed between 10-15 days after onset. Slightly elevated levels were observed 2-3 months after onset. The mean conglutinin binding test values were slightly elevated during the whole follow-up period. The severity of arthritis did not directly correlate to CIC levels. C3c and C1q-binding test were positive only in a few cases. Latex and enzyme immunoassay tests for rheumatoid factors gave low positive values in some of the sera. Agarose gel electrophoresis of serum proteins revealed non-specific changes in alpha 1-alpha 2 interzone characteristic of an acute infectious disease. The presence of CIC in the sera of patients with Pogosta disease may indicate body's natural clearange mechanisms of viral antigens. CIC may have a pathogenic role in the prolonged arthritis, even though no direct correlation with CIC levels and severity of arthritis was observed. | |
| 1812894 | Reaction of antibody to mycobacterial 65 kDa heat-shock protein with human chondrocytes. | 1991 Dec | We report on the reactivities of four monoclonal antibodies generated against mycobacterial proteins to human chondrocytes, cells in cartilage which may be subject to immune attack in rheumatoid arthritis. Only one of the monoclonal antibodies, ML30, which had been shown previously to react with a human homologue to heat-shock protein (hsp), reacted strongly to chondrocytes. By immunocytochemical methods using fixed chondrocytes, ML30 reacted to cytoplasmic constituents in a granular pattern. There were no marked qualitative differences in the staining intensities and patterns of chondrocytes kept at ambient temperatures and those subjected to 42 degrees C heat treatment. No significant staining was observed with normal peripheral blood mononuclear cells. By indirect immunofluorescence, the distribution of ML30 reactive constituents was very low on the cell surface. Reactivities of each of the monoclonal antibodies were tested on frozen sections of cartilage. Significant reactivity was found only with ML30, and the staining was only associated with chondrocytes, not with the cartilage matrix surrounding the cells. These findings may have significance in view of the possibility that an hsp homologue may be a target for inciting or perpetuating the autoimmune process in rheumatoid arthritis. | |
| 3358805 | Common tests for rheumatoid factors: poorly standardized but ubiquitous. | 1988 Mar | Rheumatoid factor (RF) test results reported in the College of American Pathologists' surveys for 1983-1985 lacked inter-laboratory reliability and mutual validity. Using the 4 most popular commercial kits for RF testing, participating laboratories consistently identified as "positive" or "negative" all but the weakly positive samples. A wide range of titers was reported on qualitative testing, however. One popular kit using a modified sheep red blood cell agglutination technique yielded results that differed markedly from those with other kits. Investigators apparently have paid little attention to these discrepancies. In Arthritis & Rheumatism, from 1983 to 1985, over 50% of the articles that referred directly or indirectly to RFs omitted details of RF methodology. Until a reliable RF test is adopted, it is essential that such methodologic information be specified. | |
| 1965930 | [Prostanoids in children with joint diseases]. | 1990 Jul | The radiological method was used to study the level of prostaglandins E + E, GF2 alpha and LTB4 in the blood plasma and the synovial fluid in 138 children with rheumatoid and other arthritis and noninflammatory diseases of the joints. The role of PGE + A and LTB4 in the pathogenesis of arthritis and low participation of PGF2 have been established. Determination of prostanoids in biological fluids can be used as an additional laboratory index to reveal the general and local activity of the pathological process in rheumatoid and other arthritis and distinguish them from noninflammatory diseases of the joints. | |
| 3063006 | D-penicillamine in juvenile chronic arthritis. | 1988 | Juvenile chronic arthritis (JCA) is a heterogeneous disease, differing in most instances from adult rheumatoid arthritis. The diagnostic criteria generally used in Europe are those proposed in Oslo in 1977. There are three main types of onset: systemic, polyarticular and pauciartricular. However, when we observe patients during the course of the disease, this proposed classification seems too simple and does not reflect the reality of outcome. To be more efficient for therapeutic studies, we think that it should be more accurate to consider the type of course, rather than the type of onset. Thus, we will discuss in a first part of this paper subdivisions of the disease according to course, biology and genetics, and indicate in which circumstances a slow acting drug such as pencillamine should be a realistic therapeutic indication. In the second part of this paper, we will give the results of already published observations and of personal data on the effect and tolerance of D-penicillamine, and discuss a way of improving drug evaluation in JCA. | |
| 3681869 | Indices of disease activity in psoriatic arthritis. | 1987 Sep | Psoriatic arthritis (PA) may respond to disease-modifying antirheumatic therapy. The value of assessing disease activity with indices devised for rheumatoid arthritis (RA) was investigated in 72 patients with seronegative PA. Thirty patients had a peripheral polyarthritis including the distal interphalangeal joints (DIPJs) and 15 a symmetrical arthritis sparing DIPJs (RA-like). Significant correlations (Spearman rank test) were seen between the clinical variables (pain score, grip strength, Ritchie articular index and a summated index of disease activity) in these two groups. Ten patients with a markedly asymmetrical arthritis showed a poor correlation between clinical variables. Although the objective indices - erythrocyte sedimentation rate (ESR) and C-reactive protein - correlated together in the first two groups, the ESR correlated solely with clinical indices, and then only in RA-like patients. These results cast some doubt on the value of assessment methods based on RA when evaluating subgroups of PA other than RA-like disease. | |
| 2400734 | Mast cells in early stages of antigen-induced arthritis in rat knee joints. | 1990 Aug | The occurrence of mast cells has been investigated in inflamed and control knee joints of rats suffering from antigen-induced arthritis, an animal model of rheumatoid arthritis in man. Rats were immunized with methylated bovine serum albumin (mBSA) followed by an intra-articular injection of mBSA (arthritis, right joints) or saline (control, left joints). Rats developed severe acute synovitis associated with cartilage erosion in the arthritic joints, whereas control joints did not show any noticeable changes. Mast cells were counted in synovial and adjacent tissues in cryostat sections of whole knee joints stained with Toluidine Blue O. The area of the synovium of each knee joint was determined using survey photomicrographs and a morphometer. Both total numbers of mast cells and frequency of mast cells in inflamed synovia were decreased after 1 day after induction of arthritis. The frequency of mast cells remained decreased up to 14 days after induction of arthritis. Morphological indications for degranulation of mast cells were never found in inflamed joints. It is concluded, therefore, that mast cells do not play a significant role in the inflammatory process during the early phase of arthritis. | |
| 3149800 | Plasma fibronectin level in patients with connective tissue diseases. | 1988 Oct | The level of plasma fibronectin (Fn) was studied in 40 patients with connective tissue diseases. Fn concentration was found increased in patients with rheumatoid arthritis (mean +/- SE, 560 +/- 30 micrograms/ml, p less than 0.01) decreased in patients with mixed connective tissue disease (337 +/- 12 micrograms/ml, p less than 0.05) and was not significantly different from controls in systemic lupus erythematosus, scleroderma, polymyositis. The value of plasma Fn level was found increased in active diseases and decreased in the cases, with presence of cryoprecipitates. The factors which might influence the level of plasma Fn and the possibility of using the changes of Fn concentration in the estimation of the evolution of connective tissue diseases are discussed. | |
| 1914182 | Measuring rheumatoid factor in nonrheumatoid subjects: immunoturbidimetric assay, latex sl | 1991 Oct | Previous studies of patients with rheumatoid arthritis (RA) have shown a good correlation between results from immunoturbidimetric assays of rheumatoid factor (RF) and latex fixation tests. To extend the research to non-RA subjects, we tested sera from 1000 pregnant women, half each in the first and third trimesters. By turbidimetry, 24 non-RA sera were regarded as positive for RF (greater than or equal to 20 int. units/mL) and 18 sera as borderline (15-19 int. units/mL). By the latex fixation test, 28 non-RA sera gave a clear reaction (positive) and 17 sera a weak reaction (borderline). The association between the tests was statistically highly significant (P less than 0.001). All sera with positive and borderline reactions were tested by enzyme-linked immunosorbent assay for RF isotypes, together with a random subsample of about one-sixth of the original serum samples. Positive RF results by immunoturbidimetry were predominantly due to the presence of IgM-RF. In contrast to some earlier findings, we saw no difference in the prevalence of positive RF reactions between sera from the first and third trimesters. | |
| 2642169 | An analysis of the frequency of Sjogren's syndrome in a population of multiple sclerosis p | 1989 Nov | We have studied 42 unselected patients with a clinical diagnosis of multiple sclerosis (MS) for clinical and laboratory features of Sjogren's syndrome (SS). The MS patients in this study had similar demographic/epidemiologic features as those previously reported in the literature. The most striking features of the MS patients suggesting a SS diathesis was the presence of dry eyes (xeropthalmia) in six (14%). Although 2/6 of the symptomatic patients and 6/36 of the asymptomatic patients had abnormal tear production (Schirmer's test) this was accounted for by the concomitant use of anti-cholinergic medication. None of the MS patients had autoantibodies (SS-A/Ro, SS-B/La, rheumatoid factor) thought to be characteristic of SS. We conclude that SS, either in isolation or occurring in combination with MS, is uncommon in an MS outpatient setting. | |
| 3394101 | [The natural course of primary Sjögren's syndrome (a clinical study)]. | 1988 | In this work the authors analyzed the clinical course and diagnostic procedures of 104 patients with primary Sjogren's syndrome (pSS): 57 patients diagnosed and followed-up at Ioannina University and 47 similar patients treated at the National Institute of Health (USA). Both studies have shown that pSS is predominantly a female disease with a latent period of 6-8 yrs from the time of the first symptom to the time of final diagnosis. Although the syndrome begins almost exclusively with glandular manifestations (xerostomia, xerophthalmia or parotid gland enlargement), in a respectable percentage of patients it eventually progresses to extraglandular involvement. pSS can be potentially complicated by benign (pseudolymphoma) or malignant (lymphoma) lymphoproliferative disorders. | |
| 2028432 | Lung function in primary Sjögren's syndrome: a cross sectional and longitudinal study. | 1991 Mar | Clinical and radiological assessment of 100 patients (97 female) with primary Sjögren's syndrome was performed within six months of diagnosis in conjunction with spirometry and measurement of transfer factor for carbon monoxide (TLCO). This was repeated in an unselected subgroup of 30 patients after a mean interval of four years. On initial assessment, 43 patients had symptoms of lung disease and 10 had related physical signs; the chest radiograph was abnormal in five. There was a significant reduction (more than 2 standardised residuals) in forced expiratory volume in one second (FEV1), vital capacity (VC), and TLCO in 14, 12, and 10 patients, 24 patients overall having a significant reduction in one or more of these measures. There was a strong relation between reduction in lung function and both pulmonary symptoms and a lip biopsy specimen positive for Sjögren's syndrome. Lung function at the initial assessment in the 30 patients who were restudied was almost identical to that of the group as a whole. Seventeen now had symptoms and nine had related physical signs. The chest radiograph was abnormal in four patients. More patients had a significant reduction in FEV1, VC, and TLCO. Lung disease is sometimes an early feature of primary Sjögren's syndrome and may progress over a relatively short period. | |
| 2168026 | Epstein-Barr virus involvement in salivary gland lesions associated with Sjögren's syndro | 1990 | Recently, Epstein-Barr virus (EBV) has gained increasing attention as a potential causative agent of Sjögren's syndrome, which is an autoimmune disorder characterized by lymphocytic infiltration of salivary and lacrimal glands. To determine the association between Sjögren's syndrome and EBV, we re-evaluated the salivary gland biopsies from patients previously diagnosed to have Sjögren's syndrome. Altogether, 20 cases of Sjögren's syndrome were reviewed from the files of the University Central Hospital since 1975. After re-evaluation of these biopsies, however, 11 patients did not fulfil the current criteria of Sjögren's syndrome, but were diagnosed as having chronic sialadenitis. All biopsies were processed for in situ hybridization (ISH) and polymerase chain reaction (PCR) to detect EBV DNA. With ISH, all samples were negative for EBV DNA. With PCR, however, 9 biopsies proved to be positive for EBV. 3 additional positive cases were found when the amplification product was dot-blotted and hybridized with EBV DNA probe. 10 of the EBV-positive salivary gland biopsies showed the histological features of chronic sialadenitis and only 2 cases were classified as having Sjögren's syndrome. On the basis of the present results, the association between EBV and Sjögren's syndrome remains doubtful. | |
| 2789655 | Clinical assessment and diagnosis of immunologically mediated salivary gland disease in Sj | 1989 Aug | Because salivary gland function and morphology can be changed by a variety of diseases and drugs, the process of clinically assessing and diagnosing salivary gland changes in patients suspected of having Sjögren's syndrome (SS) must include not just clinical recognition of the problem and assessment of its nature and severity, but identification of the cause. Determining the presence of the salivary component of SS in a patient suspected of having the disease involves three types of observations: (1) eliciting symptoms and observing signs suggesting decreased salivary function (xerostomia) during the examination, (2) objectively assessing functional or anatomical salivary changes with different types of clinical procedures that are not necessarily disease-specific, and (3) applying the most disease-specific procedures as diagnostic criteria to determine the cause of the problem. Currently used diagnostic criteria for the salivary component of SS are reviewed and compared. Alternative diagnostic criteria should be avoided if they substitute non-specific tests for more disease-specific tests. There is as yet no perfect diagnostic criterion for the salivary component of SS, but significant focal sialadenitis in a labial salivary gland biopsy is the best in terms of its disease specificity, convenience, availability and low risk. | |
| 2784958 | Exocrine pancreatic function in Sjögren's syndrome. | 1989 Apr | Pancreatic function testing was carried out in 19 patients with Sjögren's syndrome (SS) (nine primary type, ten secondary) by the N-benzoyl-tyrosil-p-aminobenzoic acid (PABA) test, serum immunoreactive trypsin (IRT) levels, and stool fat measurements to evaluate the incidence and type of exocrine pancreatic alterations in this disease. Exocrine pancreatic impairment was found to be present in 63% of the patients. Three types of secretory patterns were observed: (1) normal PABA test results and normal IRT levels (37% [7/19] of the patients); (2) normal PABA test results and elevated IRT levels (42% [8/19]; and (3) low PABA test results and elevated IRT levels (21% [4/19]), including two patients with steatorrhea. Functional pancreatic impairment tended to be more severe in patients with longer disease duration and it was related to the degree of alteration of salivary flow but not to labial salivary gland histologic changes or the type of SS. Inasmuch as hypertrypsinemia was the common marker of pancreatic dysfunction in all patients, we suggest a periodic measurement of serum IRT levels in the follow-up of patients with SS to detect early stages of pancreatic involvement. |