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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8970052 | VH4-34 (VH4.21) gene expression in the chronic arthritides of childhood: studies of associ | 1996 Dec | OBJECTIVE: To determine if the germ line gene VH4-34 (VH4.21) encodes the antimonophosphoryl lipid A (MPL) polyspecific antibodies found in oligoarticular arthritis of childhood. METHODS: Sera from a range of rheumatic diseases of childhood were assayed for VH4-34 derived antibodies by ELISA using the antiidiotype monoclonal antibody 9G4. Results were compared to assays for anti-MPL antibodies, C4d, and Bb, and for HLA type, joint count, and sedimentation rate. RESULTS: VH4-34 derived antibodies were elevated in all diseases studied except rheumatoid factor positive polyarticular disease. In oligoarticular arthritis, VH4-34 gene expression correlated with C4d concentration, and VH4-34 encoded globulins were more concentrated in synovial fluid than in blood. No association was found with HLA type. An association between VH4-34 expression and IgG anti-MPL was found in sera from patients from Cincinnati but not from Stanford. No other evidence supported a direct association between VH4-34 derived and anti-MPL antibodies in these children. CONCLUSION: The expression of VH4-34 is increased in several rheumatic diseases of childhood, but, as in adults, not in rheumatoid arthritis. VH4-34 expression is not associated with HLA type. The polyspecific autoantibody nature of some VH4-34 derived antibodies may explain the wide range of the unusual antibodies found in oligoarticular arthritis. | |
8239226 | Occurrence of antibodies to Borrelia burgdorferi in patients with nonspirochetal subacute | 1993 Dec 1 | OBJECTIVE: To determine the prevalence and specificity of antibodies to Borrelia burgdorferi in patients with nonspirochetal subacute bacterial endocarditis and assess whether increased levels of antibodies to B. burgdorferi were attributable to rheumatoid factor. DESIGN: Retrospective case-control study. SETTING: Urban referral center in an area devoid of infected ticks as a source of endocarditis sera. PATIENTS: Sera from 30 consecutive patients with culture-proven subacute endocarditis between 1979 and 1981 were compared with 30 control sera collected between 1989 and 1990. In addition, sera from 20 consecutive patients with rheumatoid arthritis who were positive for rheumatoid factor were collected between 1991 and 1992. Sera were compared with a convenience sample from 15 patients who met the criteria for Lyme disease. MEASUREMENTS: Antibodies to B. burgdorferi were assessed by enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. IgM rheumatoid factor was quantified using solid-phase radioimmunoassay or latex agglutination techniques. RESULTS: Thirteen of 30 patients with endocarditis (43%) compared with 3 of 30 normal controls (10%) had increased levels of antibodies to B. burgdorferi (P < 0.01). Of these 13 patients, only 1 had an immunoblot consistent with previous infection. The others had nonspecific immunoblots: 5 showed isolated 60-kd reactivity; 1 patient had isolated 41-kd reactivity; and 6 had no bands of reactivity. Immunoblots of the 3 controls with increased antibodies showed only isolated 41-kd reactivity. Thus, the specificity of the B. burgdorferi antibody test in patients with endocarditis was only 60% (95% CI, 42% to 78%), compared with 90% (CI, 79% to 100%) in controls. No correlation was noted between IgM rheumatoid factor and antibodies to B. burgdorferi in patients with endocarditis (r = 0.2; P > 0.2). Only 1 of 20 patients with rheumatoid arthritis without known bacterial infections had antibodies to B. burgdorferi. CONCLUSIONS: Although a positive ELISA test for B. burgdorferi may be a "true positive," a positive serologic test alone does not ensure that the clinical problem is due to Lyme borreliosis. Cross-reactive antibodies to shared epitopes between B. burgdorferi and the endocarditis organism may account for the high false-positive results. | |
8972743 | Interleukin-10 suppresses the development of collagen type II-induced arthritis and amelio | 1996 Dec | The collagen-induced arthritis model in DA rats induced with homologous rat type II collagen was chosen to determine the therapeutic capacity and effects on autoimmunity by IL-10. Systemic IL-10 treatment (100 or 10 micrograms/day) with mini-osmotic pumps during the periods of arthritis onset (days 12-20 after immunization) decreased the frequency of arthritis and delayed the onset and reduced the severity of arthritis in the few rats that eventually developed arthritis. Concomitantly, levels of autoantibodies to CII were reduced. To test the activity on established arthritis, IL-10 was administered subcutaneously in the paws. This treatment reduced the swelling but did not block the arthritis process. The effective treatment required 100 micrograms of IL-10 every 12th hour while 50 micrograms of IL-10 had little effect, although a tendency of reduced paw swelling was observed. Surprisingly, therapeutic IL-10 treatment led to higher serum levels of autoantibodies to CII. The highest doses of IL-10 (100 micrograms) did not show any apparent toxic effects when given locally or systematically. Taken together, this study suggests that IL-10 is a candidate for treatment of rheumatoid arthritis. | |
1442232 | [Bladder amyloidosis]. | 1992 Jul | We present a case of Vesical Amyloidosis (V.A.) in a woman with Rheumatoid Arthritis. Clinical data, other locations and Histochemical findings are consistent with Secondary Amyloidosis. After T.U.R., she was treated with Dimethylsulfoxide (DMSO) and Colchicine. Her severe hematuria disappeared. | |
20948025 | Chloroquine-induced photosensitive dermatoses. | 1996 May | Two female patients suffering from rheumatoid arthritis were put on chloroquine 250 mg bid. After a period of 4 weeks, both of them developed photosensitive dermatitis. Following withdrawal of chloroqunie, both of them showed improvement in dermatitis gradually over a period of 3-4 months. | |
29268046 | Sports Injury Look-Alikes. | 1994 Sep | In brief Sports medicine physicians see brief overuse, chronic, or recurrent injuries in athletes every day. However, some patients who have symptoms consistent with these injuries actually have underlying disease. Three case studies examine athletes who initially seemed to have overuse syndromes or recurrent chronic injuries. The eventual diagnoses were rheumatoid arthritis, systemic lupus erythematosus, and gout. | |
8057748 | The model of arthritis induced by superantigen in mice. | 1994 | Subcutaneous injection of Staphylococcal enterotoxin B (SEB) produced by Staphylococcus aureus, caused severe arthritis in DBA/1J mice which had been previously immunized with bovine type II collagen. The severity of this arthritis was dose dependent and prolonged joint inflammation with erosion of bone was observed. Anti- type II collage antibodies were detected in the serum of arthritic mice. Effector T cells against type II collagen were also detected by means of delayed type hypersensitivity in the skin. Moreover, a significant decrease in the ratio between T cells and B cells and an increase in the ratio between CD4+ cells and CD8+ cells was observed in spleen cells from arthritic mice. Prednisolone suppresses the induction and development of clinical signs of arthritis in mice. This evidence suggests that this experimental arthritis model may provide a means to examine the role of superantigens and the efficacy of pharmacological agents for the treatment of rheumatoid arthritis. | |
20065487 | [Measurement of rheumatoid factor - diagnostic and prognostic evaluation of patients with | 1995 Sep | Measurement of rheumatoid factor (RF) has been used for several decades both for diagnosis and prognostic evaluation of patients with rheumatoid arthritis (RA). The classical way for testing RF is by agglutination, such as the Rose-Waaler and Latex tests. In recent years, however, it has become possible to measure different RF classes by ELISA. About two thirds of routine tests carried out in the Department of Immunology at Landspitalinn in a 10 year period, 1984 to 1993, were performed on patients with diagnosed or suspected rheumatic or autoimmune conditions. RF tests alone were over 30% of all routine tests carried out during this period. In this paper a comparison is made between the information obtained by conventional agglutination tests and class specific RF tests and the literature on the clinical value of RF testing is reviewed. Many studies have showed that measurement of individual RF classes (IgM, IgG and IgA RF) is superior to conventional agglutination tests. Thus, elevation of IgA RF seems to be more specific for RA than a positive agglutination test and IgA RF positive patients have worse prognosis, both regarding the development of bone erosions and extraarticular manifestations, than patients with low IgA RF. Most RA patients have elevation of two or three RF classes, most often both IgM and IgA RF. In contrast, most patients with other rheumatic conditions have elevation of only one RF class, usually IgM RF or IgG RF. Agglutination tests can not discriminate RA patients with elevation of both IgM RF and IgA RF and poor prognosis from those who only have elevation of IgM RF and better prognosis. Furthermore, most patients with an isolated elevation of IgA RF, and poor prognosis, are negative when tested by agglutination only. It is concluded that measurement of individual RF classes give the clinicians earlier and more accurate diagnostic and prognostic information about rheumatic patients. | |
8793253 | Anaemia in juvenile chronic arthritis. | 1996 May | Anaemia is a common manifestation of juvenile rheumatoid arthritis (JCA). We have evaluated 26 JCA patients with anaemia and compared their laboratory parameters to those without anaemia. In the patients with anaemia, activation criteria such as erythrocyte sedimentation rate (ESR) and CRP were significantly higher than in those without anaemia. Anaemia was present in all systemic JCA patients and was present in 42% and 78% of the oligoarticular and polyarticular types, respectively. Serum iron levels and transferrin saturations were low in all, whereas serum iron-binding capacities of the patients were normal. Mean ferritin level was 249pg/l (range 8.46-1000pg/l). There was a significant correlation between ferritin levels and CRP and ESR (r = 0.48 and r = 0.55 respectively) (both p < 0.05). Epo levels were normal. Twelve (60%) of the bone marrow aspiration specimens stained positive for iron whereas 40% stained negative; there were also changes suggestive of myelodysplasia. Sideroblasts were also decreased in number. Thus, in these patients iron is not sufficiently transferred to the erythroid series and/or cannot be used by erythroblasts, accompanied by a possible absolute iron deficiency. Thus we suggest that the iron in JCA tends to be stored in the form of ferritin, not in an accessible form and impaired metabolism along with other factors are effective in the anaemia of JCA. | |
8730138 | Polymorphism in the LMP2 gene influences disease susceptibility and severity in HLA-B27 as | 1996 Apr | OBJECTIVE: To determine the potential contribution of the MHC class II region proteasome subunit gene, LMP2, to disease susceptibility, severity, and phenotype in patients with juvenile rheumatoid arthritis (JRA). METHODS: A CfoI restriction site polymorphism in the coding region of the LMP2 gene was evaluated in 279 patients with JRA and 107 healthy controls of similar ethnicity. Patients were divided into 5 groups on the basis of clinical presentation; 46% had early onset pauciarticular disease, 10% early onset polyarticular, 10% late onset pauciarticular, 20% late onset polyarticular, and 11% systemic onset arthritis. The influence of this LMP2 polymorphism on susceptibility to disease, clinical subtype of disease at onset (age and number of joints involved), progression and severity of joint disease (pauci to polyarticular course and radiographic changes), and occurrence of inflammatory eye disease was evaluated. RESULTS: Comparison of genotypes revealed a significantly increased prevalence of homozygosity for the LMP2 B allele (LMP2 BB genotype) in patients who were older (> or = 6 years) at onset of disease (65%, p < 0.05), particularly in those with pauciarticular (71%) involvement at presentation (p < 0.05), compared to controls (51%). The BB genotype was also more prevalent in patients with a polyarticular course, either from onset (63%) or those who progressed from pauciarticular disease (69%), compared with controls, (p = 0.05 and < 0.05, respectively). Stratification for HLA-B27 and DR4, the HLA alleles most frequently associated with late onset pauciarticular and late onset polyarticular JRA, respectively, revealed a persistent effect of LMP2 BB homozygosity on disease susceptibility and phenotype that remained statistically significant in HLA-B27 positive children, and was not due to linkage disequilibrium. CONCLUSION: We show that homozygosity of the B allele of the proteasome subunit LMP2 increases susceptibility to certain subgroups of JRA, and influences the phenotype of disease, predisposing to more progressive and severe articular disease. | |
1390962 | Evaluation of a psychological treatment package for treating pain in juvenile rheumatoid a | 1992 Jun | We examined the utility of psychological treatment procedures for children with high levels of pain associated with juvenile rheumatoid arthritis (JRA). By the use of a multiple baseline across subjects design, four children were assigned to an immediate treatment group, and four children to a delayed treatment group. The six-session treatment included relaxation training, electromyogram, and thermal biofeedback for the child; mothers were trained in the use of behavioral techniques for managing physical therapy and school attendance. Visual inspection of the data indicates small changes on children's self-reported pain diary scores for mean pain and ratings of high (greater than 5 on a 10-point visual analogue scale) pain periods, with 50% to 62% showing at least a 25% reduction in pain immediately after treatment, and 62% to 88% showing a 25% reduction by 6-month follow-up. Maternal reports of changes paralleled those of the children. Comparisons of Mann-Whitney U-tests conducted pre- and posttreatment indicated no differences for children's ratings of mean pain or +5 pain ratings between the immediate and delayed treatment groups; greater improvement for the immediate treatment group was noted on maternal reports of both mean pain (p < 0.05) and +5 pain (p < 0.5) ratings. The reduction of pain reports from pretreatment to follow-up was significant for children's mean pain (p = 0.02), +5 pain ratings (p = 0.02), and mother's reports of mean pain (p = 0.03) and +5 pain periods (p = 0.01). Maternal reports of the number of pain-related behaviors that the child exhibited also declined (p < 0.05). No reduction in physical therapist's ratings of pain during evaluation were noted. No increases in maternal reports of child's psychological adjustment problems were reported following treatment. Results provide modest support for the use of psychological interventions with patients with JRA. | |
1437440 | Epidemiology of juvenile chronic arthritis in southwestern Sweden: a 5-year prospective po | 1992 Dec | Previous epidemiological studies of juvenile chronic arthritis (JCA) report divergent results owing to differences in diagnostic criteria, patient retrieval, and study designs. To investigate incidence and prevalence of JCA in a total population, this prospective survey was performed in southwestern Sweden between 1984 and 1988. Cases were identified using the European League Against Rheumatism criteria for JCA and were reported annually from eight pediatric departments and local pediatricians in the studied area. During the 5 years, 213 new cases of JCA were found, corresponding to an incidence of 54.6 per 100,000 children younger than 16 years of age. The average annual incidence was 10.9 per 100,000. The peak incidence rate, 18.3 per 100,000 was found in girls 0 through 3 years old. The lowest incidence rate, 6.4 per 100,000, was found among boys 12 through 15 years old. In December 1988, 334 cases of JCA were recorded, giving a prevalence of 86.3 per 100,000. When patients in remission were omitted the prevalence was 64.1 per 100,000. The monoarticular+pauciarticular onset type constituted 68.3% of the prevalence cases, while 21.9 were polyarticular and 6.6% had systemic onset. To avoid underestimation of incidence and prevalence, and to get a correct picture of disease patterns, epidemiological surveys of JCA should be population-based rather than referral center-based. Further descriptive studies of JCA in different well-defined geographic areas are important to make valid comparisons. Such comparisons could give clues to etiological factors, both genetic and environmental. | |
8986662 | Revision of the acetabular component of a total hip arthroplasty with cement in young pati | 1996 Dec | The results for eighty-two young patients without rheumatoid arthritis who had had eighty-seven revisions of the acetabular component because of aseptic loosening were studied. The mean duration of follow-up was approximately six years (range, 1.9 to 18.1 years). The clinical result was excellent or satisfactory for seventy-nine hips (91 per cent). However, at the latest radiographic assessment, twenty-six sockets were loose. Of the fifty hips that had had good bone stock (only slight enlargement of the acetabulum or local defects involving only one wall) before the revision, seven (14 per cent) had loosening of the socket, compared with nineteen (51 per cent) of the thirty-seven that had had poor bone stock (massive or global collapse of the acetabulum and defects involving at least two walls). The relationship between loosening and the quality of the bone stock before the revision was highly significant (p = 0.0002, chi-square test). The results of revision of the socket with use of cement and without use of any bone grafts in young patients who have poor acetabular bone stock are not very encouraging. The need for regular follow-up of all patients who have had an arthroplasty cannot be overemphasized. | |
8712889 | Gastrointestinal involvement in Behçet's syndrome: a controlled study. | 1996 Mar | OBJECTIVE: To make a retrospective and prospective analysis of the frequency of symptomatic inflammatory bowel disease in patients with Behçet's syndrome (BS). METHODS: The medical records of the first 1000 patients with BS were reviewed retrospectively for past or present history of diarrhoea. The past and present history of diarrhoea was also elicited prospectively among 147 consecutive patients with BS and 78 diseased controls (42 with rheumatoid arthritis, 17 with systemic lupus erythematosus, seven with seronegative spondylarthropathy, and 12 with miscellaneous rheumatic diseases). Inflammatory mucosal changes were sought in rectal biopsy specimens from 75 patients with BS, 47 diseased controls (29 with nephrotic syndrome, eight with rheumatoid arthritis, six with familial Mediterranean fever, and four with ankylosing spondylitis), and 14 patients with ulcerative colitis. RESULTS: In chart review there were only seven Behçet's patients with diarrhoea; none of them had inflammatory bowel disease. In the prospective survey there were no significant differences between the BS and control groups in the past and present history of diarrhoea. There were no significant differences in the rectal mucosal histology between patients with BS and controls, while patients with ulcerative colitis showed pronounced differences. CONCLUSION: Symptomatic inflammatory bowel disease is not common in BS patients from Turkey. | |
7928639 | The joint capsule: structure, composition, ageing and disease. | 1994 Jun | The joint capsule is vital to the function of synovial joints. It seals the joint space, provides passive stability by limiting movements, provides active stability via its proprioceptive nerve endings and may form articular surfaces for the joint. It is a dense fibrous connective tissue that is attached to the bones via specialised attachment zones and forms a sleeve around the joint. It varies in thickness according to the stresses to which it is subject, is locally thickened to form capsular ligaments, and may also incorporate tendons. The capsule is often injured, leading to laxity, constriction and/or adhesion to surrounding structures. It is also important in rheumatic disease, including rheumatoid arthritis and osteoarthritis, crystal deposition disorders, bony spur formation and ankylosing spondylitis. This article concentrates on the specialised structures of the capsule--where capsular tissues attach to bone or form part of the articulation of the joint. It focuses on 2 joints: the rat knee and the proximal interphalangeal (PIP) joint of the human finger. The attachments to bone contain fibrocartilage, derived from the cartilage of the embryonic bone rudiment and rich in type II collagen and glycosaminoglycans. The attachment changes with age, when type II collagen spreads into the capsular ligament or tendon, or pathology--type II collagen is lost from PIP capsular attachments in rheumatoid arthritis. Parts of the capsule that are compressed during movement adapt by becoming fibrocartilaginous. Such regions accumulate cartilage-like glycosaminoglycans and may contain type II collagen, especially in aged material.(ABSTRACT TRUNCATED AT 250 WORDS) | |
7684959 | The expression of major histocompatibility antigens on human articular chondrocytes. | 1993 Jun | Human articular chondrocytes were analyzed for major histocompatibility (MHC) antigens. The cells were obtained by enzymatic digestion of surgical specimens from patients with osteoarthrosis and rheumatoid arthritis having joint replacement. The analyses of Class I and Class II antigens were performed using microcytotoxicity techniques, as with conventional human leukocyte antigen (HLA) typing, and by immunofluorescence on a flow cytometer with monoclonal antibodies. Eighty-five percent of the chondrocytes had strong representation of Class I molecules, and individual specificities for HLA-A, HLA-B, and HLA-C could be detected. Class II antigens generally were not expressed on chondrocytes from noninflammatory states. In osteoarthrosis, some cells expressed HLA-DP and HLA-DQ, whereas in rheumatoid arthritis, there was an increase in the expression of all Class II antigens. Incubation of chondrocytes with gamma-interferon caused the strong induction of HLA-DR and HLA-DP, whereas HLA-DQ expression was largely unaffected. These results have broad implications for tissue transplantation and autoimmune disease. | |
1347283 | Polymorphism in a T-cell receptor variable gene is associated with susceptibility to a juv | 1992 | This report demonstrates a T-cell receptor (Tcr) restriction fragment length polymorphism, defined by a Tcrb-V6.1 gene probe and Bgl II restriction enzyme, to be absolutely correlated with allelic variation in the coding sequence of a Tcrb-V6.1 gene. A pair of non-conservative amino acid substitutions distinguish the Tcrb-V6.1 allelic variants. An association of this Tcrb-V6.1 gene allelic variant with one form of juvenile rheumatoid arthritis (JRA) was established in a cohort of 126 patients. The association was observed in patients possessing the HLA-DQA1*0101 gene. Among HLA-DQA*0101 individuals, 19 of 26 patients (73.1%) carried one particular Tcrb-V6.1 gene allele as opposed to 11 of 33 controls (33%; p less than 0.005). Haplotypes carrying this HLA gene have previously been shown to confer increased risk for progression of arthritis in JRA. This demonstration of a disease-associated Tcrb-V gene allelic variant has not, to our knowledge, been previously reported and supports the contribution of polymorphism in the Tcr variable region genomic repertoire to human autoimmune disease. | |
19078095 | TJ-114 (Sairei-To), an Herbal Medicine in Rheumatoid Arthritis. | 1996 Dec | The search for better treatments for malignancies has been enhanced by use of a relatively inexpensive clinical protocol that encourages the preliminary screening of a large number of potential anticancer drugs with early elimination of those that are clearly ineffective, preserving resources for more intensive evaluation of those that show some evidence of benefit. We adapted this method to determine whether the herbal medicine TJ-114 was worthy of further study for the treatment of rheumatoid arthritis (RA) patients. TJ-114 is a traditional herbal medicine that has been used extensively in Japan for the treatment of RA, Reports suggest that it may be a useful second-line agent, well-tolerated and safe. For these reasons, a 6-month, open prospective pilot study to evaluate the efficacy, safety and tolerability of TJ-114 in United States RA patients was undertaken. Thirty patients were enrolled; 18 completed the study. There were five responders by predefined composite criteria. Twelve patients withdrew from the trial, six for lack of efficacy, four for non-compliance, one for diarrhea and one for constipation and abdominal pain. The anti-cancer drug screening protocol stipulates that the drug be discarded if there are no responders among the first 14 patients and only 1 or 2 among the first 30 patients. Using this approach, the response rate found in this study justifies placebo-controlled, double-blind studies to determine the relative efficacy and toxicity of TJ-114 in a more definitive manner. | |
19077974 | Tetracyclines may be therapeutically beneficial in rheumatoid arthritis. | 1995 Jun | Several clinical trials have been conducted in the past 3 years using minocycline as an anti-inflammatory agent for rheumatoid arthritis (RA), Depending on one's viewpoint, these trials have or have not shown a mild beneficial effect on conventional RA parameters of inflammation. In the context of currently available anti-inflammatory therapy, the magnitude of the reported effects would not seem to justify additional large scale trials. There is, however, compelling basic science data as well as preliminary clinical data, suggesting that certain tetracyclines may have a valuable role to play in treatment of RA. There is even reason to believe that such an agent could be the Holy Grail of rheumatology, namely the drug that prevents connective tissue degradation in destructive arthritides. This concept is based on the properties of tetracyclines as inhibitors of matrix metalloproteinases. In this article, the properties of the tetracyclines in this regard are reviewed, and concepts are suggested for the design of a trial addressing the unique properties of these drugs. | |
7742157 | Methylprednisolone-hemisuccinate and its metabolites in serum, urine and bile from two pat | 1995 Feb | Methylprednisolone-hemisuccinate (MPHS), methylprednisolone (MP), 20-alpha-hydroxy- (20 alpha HMP) and 20-beta-hydroxymethyl-prednisolone (20 beta HMP) concentrations were measured in serum, urine and bile from two liver transplant recipients who had received 1 g MPHS by a 1 h intravenous infusion for treatment of an acute rejection episode. These patients excreted similar total amounts of the dose in urine as patients with rheumatoid arthritis (historical controls) who had normal liver function. The transplant patients showed a ratio in urine of 'total metabolites'/MPHS that was one third that of patients with rheumatoid arthritis. Less than 0.2% of the administered MPHS appeared in bile as MPHS, MP, 20 alpha HMP and 20 beta HMP during the 24 h following infusion. Liver transplantation did not affect the overall elimination of drug in urine. However, the impaired liver function following transplantation resulted in reduced conversion of MPHS to its active form (MP). |