Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
---|---|---|---|---|
2784219 | High rate of HLA class II mRNA synthesis in rheumatoid arthritis joints and its persistenc | 1989 Jan | The expression of HLA class II mRNA was investigated in the joints of patients with active rheumatoid arthritis (RA) in order to evaluate patterns of synthesis. Northern hybridization analysis showed that HLA class II gene transcripts in RA joints were of the correct sizes, and subsequent analyses were performed by slot blotting. All active RA samples expressed high levels of HLA-DR, DP, and DQ mRNA with DP and DQ less than DR. Synovial fluid or membrane cells, chiefly a mixture of T cells and macrophages, were placed in culture, in the absence of any stimulation. The levels of mRNA remained at a high level in vitro. The half of HLA-DR mRNA in joint cells was very brief (approximately 30 min), indicating that prolonged synthesis was due to restimulation of the cells. The effect of lymphokines on HLA class II regulation on joint cell was assessed. Gamma interferon was capable of augmenting HLA-DR to some extent, but paradoxically interleukin 2 at concentrations optimal for stimulating T cells, diminished HLA-DR expression. | |
1684124 | Immunodeficiencies associated with sulphasalazine therapy in inflammatory arthritis. | 1991 Dec | Abnormalities in serum immunoglobulin levels (Igs) are documented in a series of 350 patients with rheumatoid arthritis (RA) and other inflammatory joint diseases treated with sulphasalazine (SASP) for up to 10 years. Low Ig levels occurred in just over 10% of patients after therapy. Three per cent developed selective IgA deficiency between 8 and 20 weeks after starting SASP. Low IgG levels occurred in 2% at 4-52 weeks and low IgM levels in 5% after 3-7 months. One per cent developed panhypogammaglobulinaemia (hypo gamma) 3-7 months after commencing therapy. Most immunodeficiencies were not accompanied by other toxic reactions and SASP was continued in all but one patient with a rash and thrombocytopenia. A good clinical response was observed in most patients particularly those with selective IgA deficiency and hypo gamma. Two patients with hypo gamma developed chest infections which responded to antibiotics. A low level of individual Igs is not usually an indication to stop SASP unless accompanied by other reactions. Panhypo gamma is potentially serious and should be monitored carefully and replacement therapy should be considered in these patients if infections occur. | |
3006610 | Studies of the effect of D-penicillamine and sodium aurothiomalate therapy on superoxide a | 1986 Jan | The capacity of monocytes from patients with rheumatoid arthritis to generate superoxide anion in vitro after stimulation with serum treated zymosan (STZ) or IgG treated zymosan (IgTZ) was studied before and during therapy with penicillamine (n = 9) or sodium aurothiomalate (AuTM) (n = 12). Significant increases in rates of STZ (p less than 0.01) and IgTZ (p less than 0.02) stimulated superoxide anion production were seen after successful therapy (14 patients), which were paralleled by a significant increase in serum thiol levels. Patients who did not respond clinically to therapy (n = 4) showed a smaller mean increase in serum thiol levels and had high mean rates of in vitro superoxide production before and after second-line therapy. Three patients were withdrawn from the study. The data suggest that successful therapy with penicillamine or AuTM may be associated with monocyte activation, and possible mechanisms are discussed. | |
3581568 | Revision knee arthroplasty in rheumatoid arthritis. | 1987 Jun | Seventy-six revised total knee arthroplasties (TKAs) performed for mechanical, nonseptic failure of the primary arthroplasty in 62 rheumatoid arthritis patients were investigated. The revisions were performed with McIntosh, Marmor, Attenborough, Guepar, and various types of tricompartmental prostheses. Twenty-one of the 76 revisions subsequently failed. Fifteen were mechanical failures and six were deep infections. Thirteen of the 21 failures were treated with another arthroplasty, six with arthrodesis, and two with antibiotics only. After an average of 60 months, 48 of the surviving arthroplasties were examined clinically and roentgenographically. At follow-up examination, eight were clinical failures. One-half of the McIntosh and Marmor arthroplasties and one-third of the Attenborough and Guepar arthroplasties, altogether 17 cases, showed signs of potential roentgenographic failure. The majority of the revised TKAs classified as roentgenographic failures were clinically successful or acceptable. Revision of TKAs in noninfected rheumatoid patients can be performed with acceptable clinical results but with a significantly higher failure rate than after primary procedures. | |
2491031 | [Double heart prosthesis in a patient with rheumatoid arthritis]. | 1989 Jan | The incidence of rheumatoid valvular disease is among 2.5% to 30% of necropsy patients with rheumatoid arthritis. The valves may be affected by a granulomatous form patognomonic, or by unspecific inflammatory changes (the most frequent 90-99%). We present a patient affected by a classical seropositive rheumatoid arthritis accompanied by mixed stenosis and incompetence of both mitral and aortic valves. The patient underwent replacement of both valves, and typical unspecific inflammatory changes were detected histologically in the valvular tissues. Replacement of the valves by a prosthesis is the choice treatment despite severe joint disease. The echocardiography is the ideal method for detection of cases with subclinic lesions and to continue evolution. | |
3753537 | Urinary neopterin reflects clinical activity in patients with rheumatoid arthritis. | 1986 Sep | Neopterin is a marker for activation of cellular immunity. Urinary neopterin levels were measured in 106 patients with rheumatoid arthritis (RA) and in 45 patients with osteoarthritis. Levels were significantly higher in RA patients than in osteoarthritis patients and were strongly dependent on stage and activity of RA. Correlations with other laboratory parameters were weak. Multivariate analysis demonstrated that urinary neopterin levels reflected clinical activity better than did other laboratory findings. Thus, urinary neopterin determination might be useful in monitoring RA patients. | |
1887429 | [Prostaglandins in the blood serum of patients with rheumatoid arthritis]. | 1991 | Radioimmunoassay was used to study the content of prostaglandins in blood plasma of patients suffering from rheumatoid arthritis (PGE in 133 and PGF2 alpha in 102 patients). It has been established that as compared to the control group subjects, it is appreciably elevated and reflects the degree of inflammatory process activity, being pronounced to a greater measure in persons not receiving glucocorticoids than in hormone-dependent patients. A relationship has been revealed between the content of PGE and PGF2 alpha and certain clinical and laboratory characteristics (disease standing, intensity of exudative component of inflammation, the presence of humoral and cellular immunity disorders, anemia, and some visceral lesions), which may be of definite importance in the assessment of the patient's status. The time-course of changes in blood plasma prostaglandins reflects on the whole the dynamics of the disease activity, being related to a greater degree to the application of nonsteroidal antiinflammatory agents than of glucocorticoids. | |
3780140 | Prednisolone pharmacokinetics in patients with rheumatoid arthritis, polymyalgia rheumatic | 1986 Sep | The pharmacokinetic profile of a single 10 mg oral dose of prednisolone was studied in three groups of six patients with rheumatoid arthritis (RA), polymyalgia rheumatica (PMR) and bronchial asthma (BA) who were already receiving steroid therapy. A fourth group of age and sex-matched normal controls was also studied. Kinetic parameters (including elimination half-life, area under the plasma concentration curve, apparent volume of distribution and total body clearance) were similar for all four groups but there was considerable inter-subject variability. The correlations between these kinetic parameters and age, body weight and serum albumin were poor. The results suggest that any differences in the effects of corticosteroids in these inflammatory diseases are unlikely to be due to pharmacokinetic factors. The duration of steroid therapy and the reduction in patient mobility would appear to be more likely explanations for the reduction in bone mass observed in patients with RA. | |
3580715 | Renal and pancreatic calcification in rheumatoid arthritis with Sjögren's syndrome. | 1987 Jun | We describe a female patient who developed seropositive rheumatoid arthritis (RA) at the age of 12 years. After 10 years her disease was complicated by Sjögren's syndrome (SS) and distal (type 1) renal tubular acidosis (RTA). Seven years later she was noted to have nephrocalcinosis. At the age of 32, investigation of a short history of weight loss and abdominal pain revealed a benign gastric ulcer and chronic calcific pancreatitis. We believe she is the first patient with RA and SS in whom complicating renal and pancreatic calcification have been reported. Her case emphasizes the good prognosis of type 1 RTA in SS and suggests that pancreatic involvement may be more common than clinically apparent. | |
2512583 | A specific HLA-DP beta allele is associated with pauciarticular juvenile rheumatoid arthri | 1989 Dec | Nonradioactive sequence-specific oligonucleotide probes specific for the HLA-DP beta locus have been used in a simple dot-blot format to type samples amplified by the polymerase chain reaction from 44 patients with pauciarticular juvenile rheumatoid arthritis, 32 patients with adult rheumatoid arthritis, and 50 random controls. The sequences of four new DP beta alleles derived from these patients and controls are reported, bringing the total number of alleles identified thus far to 19. The DPB2.1 allele is significantly increased in juvenile rheumatoid arthritis patients over controls; this allele is not increased in patients with adult rheumatoid arthritis. The association of juvenile rheumatoid arthritis with the DPB2.1 allele is independent of linkage with previously defined HLA-D region markers of disease. Analysis of the DPB2.1 sequence shows that it differs from the nonsusceptible DPB4.2 allele by only 1 amino acid at position 69 in the beta 1 domain. | |
2659124 | A comparison of measures of health status in rheumatoid arthritis. | 1989 Jun | One hundred and five patients with rheumatoid arthritis were assessed on two occasions separated by 15 months, by means of the ARA functional scale, the Mallya and Mace index, the Health Assessment Questionnaire (HAQ) and the Functional Limitations Profile (FLP). Thirty three per cent of patients were assessed as clinically changed in terms of the ARA scale. On both occasions cross-sectional correlations were strongest between the health status measures (HAQ and FLP) and grip strength and the Ritchie articular index. The sensitivity and specificity of the two health status measures in relation to clinical change were calculated and overall the HAQ and FLP achieved similarly modest levels of sensitivity and specificity. The greater amount of precision and information provided by the FLP has to be weighed against the simpler measurement assumptions and shorter time required to administer the HAQ. | |
3690984 | A prospective study of early onset rheumatoid arthritis over fifteen years: prognostic fea | 1987 Sep | A total of 218 patients with early onset rheumatoid arthritis were entered into a prospective study over fifteen years. Of these, 151 remained in the study at three years (of whom 14 died), and a further 39 (23 deaths) defaulted after this time. The severity of disease was assessed by four different methods. Although persistently active joint disease was recorded in 26% of patients, only 13% had severe functional impairment, and only 14% developed severe erosions. An episode of RA lasting two to three years followed by complete remission with none or minimal sequelae ("non recurrent" RA) was present in 34%. Using discriminant analysis, which selected rheumatoid factor, haemoglobin level and platelet count from a number of clinical and laboratory variables measured at onset, it was possible to predict three mutually exclusive outcome categories correctly in 50-60% of patients depending on the method of assessment of outcome. | |
2501634 | Ginger (Zingiber officinale) and rheumatic disorders. | 1989 May | Oxygenation of arachidonic acid is increased in inflamed tissues. In this condition products of two enzymic pathways--the cyclooxygenase and the 5-lipoxygenase producing respectively prostaglandins and leukotrienes--are elevated. Of the cyclooxygenase products, PGE2 and of the lipoxygenase products, LTB4 are the strongest candidates for mediating inflammation. Non-steroidal anti-inflammatory drugs which inhibit the cyclooxygenase, and corticosteroids are used to treat such disorders. Both types of drugs produce adverse side-effects on prolonged use. Ginger is reported in Ayurvedic and Tibb systems of medicine to be useful in rheumatic disorders. Seven patients suffering from such disorders reported relief in pain and associated symptoms on ginger administration. | |
1721847 | Identification of antibody epitopes within the CB-11 peptide of type II collagen. II. Comp | 1991 | Computer modelling techniques were used to investigate the structure of 8-mers from the CB-11 peptide of bovine type II collagen which were recognised by sera from rats which had previously been injected with bovine type II collage. It was discovered that all the hydrophobic peptides recognised by the rat sera were predicted to have collagenous-like secondary structures. The primary structure of the 8-mers which were recognised was also compared against the sequences in the OWL protein sequence database. The combined results of the computer modelling and sequence analysis suggested that the sequence Gly-Pro-Gly-Phe-Pro is a minimal B cell epitope of the CB-11 fragment of bovine type II collagen. | |
2181126 | A new method of screening for vertical atlantoaxial dislocation. | 1990 Feb | A new method for the screening and grading of vertical atlantoaxial dislocation is described. The Sakaguchi-Kauppi method is based on a pathologic process in the atlantoaxial joints and the grading system gives a reproducible (interobserver coefficient of variation = 0.062) tool for the screening of vertical dislocation and is also applicable to patients for whom earlier radiographs are not available. There were differences between the results obtained using Redlund's method and the new Sakaguchi-Kauppi method (chi 2 = 44.7, p less than 0.001). This difference stems from the variations in the height of the axis in the normal population and results in a sensitivity and specificity of 84.2% and 90%, respectively, for Redlund's method compared to the new method. | |
1688406 | Cross-reactivity between the EBNA-1 p107 peptide, collagen, and keratin: implications for | 1990 Jan | An unusually heavy load of Epstein-Barr virus (EBV) infection and autoimmunity to collagen are believed to be contributing factors to the pathogenesis of rheumatoid arthritis (RA). The present report presents data showing that p107, the major epitope of the EBV-encoded EBNA-1 antigen, cross-reacts with denatured collagen (DC) and keratin (K), suggesting a new likely link among RA, EBV-1, and these autoantigens. A radioimmunoassay using antigen-coated microtiter plates was used to demonstrate antibodies in sera of patients with RA and sera of healthy donors against p107, DC, and K. Specificity of the antibodies was ascertained by inhibition tests with the homologous antigens. Cross-reactivity among anti-p107, anti-DC, and anti-K antibodies was assayed by the ability of a given antigen to block the binding of nonpurified or affinity-purified antibodies to plates coated with another antigen. Most of the sera contained antibodies to all three antigens, but only anti-DC antibodies were present in higher titers in RA sera. Preincubation of sera with p107 appreciably reduced their binding to plates coated with DC or K. On the other hand, preincubation with DC (in solution or bound to Sepharose) did not result in consistent reduction of anti-p107 titers. Tests with affinity-purified antibodies revealed the existence of two antibodies populations, one of which reacted preferentially with p107, the other with DC. The cross-reactivity of the anti-p107 antibodies with DC and K suggests that such antibodies, produced by RA patients following persistent stimulation with EBV, might react in vivo with collagen (and keratin) exposed in previously damaged areas and thus reinforce the disease process. | |
3179625 | Functional assessment of early rheumatoid arthritis. | 1988 Oct | A new performance index, SOFI (Signals of Functional Impairment), is described. This aims to detect functional impairment of different joints as early as possible. It comprises assessments of hand, arm and leg function. The assessment time is short and reliability is satisfactory. The index correlates significantly with range of motion, Ritchie index, grip strength, and the Stanford Health Assessment Questionnaire (HAQ) disability index. The last mentioned was used in parallel with the new index to study 50 early RA patients. These were followed every 3-6 months for 1 year. Both indices seemed to fluctuate with changes in the patient's state. | |
3029860 | [Vasculitic polyneuropathy as a complication in chronic polyarthritis]. | 1986 Dec 27 | Polyneuropathy due to vasculitis in connection with rheumatoid arthritis is a rare complication of the disease. Special investigations can help us to distinguish between a peripheral sensory-neuropathy with a good prognosis, the neuropathy of the autonomous nervous system and the severe form of mononeuritis multiplex. The bad prognosis of this form is due to the diffuse vasculitis of internal organs. We describe 5 patients with rheumatoid arthritis and different forms of vasculitis. The differential diagnosis, therapy and prognosis are described in detail. | |
1694247 | Activated lymphocytes in the peripheral blood of patients with rheumatoid arthritis. | 1990 May | The peripheral blood and synovial fluid of patients with rheumatoid arthritis (RA), when compared to controls, has a higher proportion of mononuclear cells actively synthesizing DNA (S-phase cells). Such cells can be marked by radioautography after incubation with tritiated thymidine and can also be quantitated by the 4-h spontaneous in vitro uptake of tritiated thymidine. As our previous studies showed a marked and rapid decrease in this latter measure, in response to in vivo methotrexate, we suggested that the responsible cells may have a direct role in pathogenesis rather than merely reflecting the inflammation that is present. We have therefore tried to characterize them further. A mean of 46% of these autoradiography positive cells from the peripheral blood of patients with active RA bear CD3 markers and 61% Ia. On some occasions up to 25% stain for Leu M3 and 25% for Leu 7. None were esterase positive. Cell separation studies confirm that such cells were found in both T cell and non-T cell enriched populations. These cells, therefore, appear to be heterogeneous. A decreased number was seen in peripheral blood lymphocytes from patients who had received remittive therapy for over 4 months when compared to other patients with RA and this was associated with a lower 4-h spontaneous uptake of labelled thymidine. | |
2825478 | Effects of tilomisole, indomethacin and levamisole on regulation of Epstein Barr virus-ind | 1987 Aug | When activated in autologous mixed leukocyte reactions (auto-MLR) in vitro, T cells from normal individuals produce a suppressor factor(s) which inhibits the Epstein-Barr virus (EBV)-induced proliferation of normal B cells. In contrast, T cells from patients with rheumatoid arthritis (RA) are deficient in their ability to generate this suppressor factor in auto-MLR. Addition of tilomisole (Wy-18,251; 33(p-chlorophenyl)thiazolo[3,2-a]benzimidazole-2-acetic acid) to the auto-MLR (0.1-100 micrograms/ml) did not alter the production of suppressor activity by normal T cells, but 100 micrograms/ml tilomisole restored to normal the defective factor production by RA T cells. Indomethacin (1 microgram/ml) but not levamisole (0.1-100 micrograms/ml) had a similar effect, which suggests that the action of tilomisole in this system is due to its ability to inhibit prostaglandin biosynthesis. Nonetheless, the ability of tilomisole to down-regulate B cell function may contribute to the compound's antiarthritic activity. |