Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 8119046 | Clinical pharmacokinetics in the treatment of rheumatoid arthritis in pregnancy. | 1993 Dec | Rheumatoid arthritis is a relatively common problem in women of reproductive age. Pregnancy may affect all aspects of the pharmacokinetics of the drugs used in its treatment. The effects of pregnancy on the pharmacokinetics of drugs are, for the most part, not clinically significant. The pharmacokinetics of placental transfer and fetal safety have been specified for many drugs. Drugs used in rheumatoid arthritis can be classified into 3 classes: those with the greatest safety for the fetus, those that are unsafe for the fetus, and those for which there are insufficient data to determine the risk to the fetus. | |
| 7888428 | [Magnetic resonance tomography of finger polyarthritis: morphology and cartilage signals a | 1995 Jan | This report deals with a prospective study of 21 patients with finger osteoarthritis treated over a period of three months with either Ademetionin (therapy group: 14/21) or without (control group: 7/21). MR-Imaging was carried out before and after treatment using spin-echo and 3D-Flash sequences. Morphological parameters and signal intensity changes of the hyaline cartilage were evaluated. The increase of the cartilage signal intensity was significant in the therapy group, this can be interpreted as an structural improvement. Also a decrease of the cartilage signal intensity with age was found. The morphological parameters showed no significant changes in the therapy and control groups. | |
| 7481588 | Rheumatic pains of previously undiagnosed diabetic subjects. | 1995 | To identify the early diabetic musculoskeletal symptoms of previously undiagnosed diabetic subjects, a case-control study was carried out. The cases and controls were recruited from a population aged 55 years. Questions concerning the symptoms were asked before the 2-h oral glucose tolerance tests (OGTT). The results show that pain in the right hand was the most prominent symptom among the diabetic women. Pains in the left hand and the shoulders in the diabetic women and pains in the right knee and the right hip joint in the diabetic men tended to be more prevalent than the corresponding symptoms in the controls. The highest prevalence of most musculoskeletal pains occurred in the highest tertile of 2-h OGTT values among women. The conclusion is that the hand pain is closely associated with the development of diabetes and may give clues to an early diagnosis of diabetes in a middle-aged population. | |
| 7639806 | A randomized, double-blind, placebo-controlled study of CD4 monoclonal antibody therapy in | 1995 Aug | OBJECTIVE: To assess the efficacy of the CD4 monoclonal antibody (MAb) cM-T412 in the treatment of early rheumatoid arthritis (RA). METHODS: Sixty patients were enrolled in a 6-week randomized, double-blind, placebo-controlled study investigating multiple dose regimens of cM-T412. Thirty patients subsequently were enrolled in a 9-month randomized, double-blind, placebo-controlled study investigating monthly single-dose administrations of cM-T412. RESULTS: Analysis of clinical parameters revealed no changes in arthritis activity in the groups that received CD4 MAb or the placebo group, and no difference between the groups, in either in the first or the second part of the study. The number of circulating CD4+ cells decreased substantially in the patients treated with CD4 MAb. CONCLUSION: CD4 MAb treatment of patients with early RA induced no therapeutic effect. | |
| 1570520 | Contribution of synovial mesenchymal cells to the pathogenesis of rheumatoid arthritis. | 1992 Feb | Rheumatoid joint destruction is caused by (1) enzymatic digestion from articular surfaces of cartilage, (2) pannus formation, and (3) lysis of the matrix by activated chondrocytes. Pannus, a vascular and fibrous granulation tissue arising from the perichondral synovial membrane, extends onto cartilage surfaces as a layer of morphologically quiescent fibroblastic mesenchymal cells. Pannus subsequently starts invasion into cartilage matrix with the appearance of macrophagelike cells. Synovial mesenchymal cells are thought to play important roles in the pathogenesis of rheumatoid joint destruction in relation to la expression and antigen presentation as well as the elaboration of inflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha. By experimentally inducing antigen-induced arthritis in H-2-c-fos transgenic mice whose immunoglobulin G antibody response against immunizing antigen was defective, the investigators produced destructive arthritis without lymphocyte infiltration. The only cells invading the joints in these mice were similar to a previously recognized subset of human synovial cells that had a mesenchymal appearance. These mesenchymal cells invaded the cartilage matrix upon in vitro culture. The role of synovial mesenchymal cells in the pathogenesis of rheumatoid joint destruction is discussed. | |
| 8216817 | Localization of the angiogenesis inhibitor thrombospondin in human synovial tissues. | 1993 | Recently, we have shown that a macrophage subpopulation isolated from the synovial tissue of patients with rheumatoid arthritis was potently angiogenic and that a secreted inhibitor of angiogenesis, which is controlled by a tumor suppressor gene in hamster cells, was similar to thrombospondin. In order to investigate the potential role of thrombospondin in human arthritic disorders, we employed immunohistochemistry to examine frozen synovial tissue sections from normal controls (n = 3), patients with rheumatoid arthritis (n = 14) and with osteoarthritis (n = 5). The synovial tissues were stained with monoclonal antibody (mAb) A2.5, which reacts with the heparin-binding domain of thrombospondin, mAb A6.1, which reacts with the epidermal growth factor repeat motif of thrombospondin, and with mAb A4.1, which reacts with the properdin-repeat domain of thrombospondin. In rheumatoid synovial tissues the anti-thrombospondin mAbs reacted with vascular endothelial cells, and to a lesser extent with vascular smooth muscle. Pericytes were stained, particularly with mAb 6.1. Reactivity was also found with isolated macrophages and with the macrophage-derived synovial lining layer in over half the tissues. In osteoarthritis synovial tissues, mAb A2.5 stained fewer macrophages than in rheumatoid arthritis synovial tissues. Slightly fewer blood vessels reacted with mAb A2.5 in normal compared to diseased synovia. The mAbs reacted with capillaries, venules and arterioles in all synovial tissues. We conclude that mAbs to thrombospondin react primarily with blood vessels and macrophages in synovial tissues. Perhaps thrombospondin may function as an adhesive glycoprotein mediating cellular interactions, or it may serve to counteract the effects of the angiogenic factors produced by cells within diseased synovial tissues. | |
| 1460382 | Tissue reactions at the implant-bone interface of the cementless total knee prostheses wit | 1992 Oct | Periprosthetic tissues of 14 revised knees of 11 patients, who had undergone Mark-II type cementless total knee prosthesis, were examined to find the relationship between tissue and sinking. Nine patients had rheumatoid arthritis and two had osteoarthritis. Two types of tissue reactions were observed at the implant-bone interface: 1) granulation-dominant tissue, composed of giant cells and macrophages phagocytizing high density polyethylene flakes and dense granules of metal, on the femoral side in six cases, and tibial side in four, 2) fibrosis-dominant tissue on the tibial side in seven, and femoral side in four. On each type, three zones were observed. In the deep zone adjacent to the bone, hyaline cartilage-like tissue was located on the tibial side in four cases, and femoral side in one. An immunohistochemical stain with S-100 proteins and transmission electron microscopy revealed chondrocyte-like features. Chondrogenesis was more frequently observed on the tibial side. | |
| 8845054 | Orthotopic implantation of inflamed synovial tissue from RA patients induces a characteris | 1996 Feb | The objective of this work was to study in more detail the human/murine SCID arthritis model with special emphasis on characteristic features initiated by rheumatoid arthritis (RA) synovial membrane (SM) as compared to appropriate control tissues. Small tissue samples from RA-SM, healthy lymph node, healthy SM, and granulomatous tissue of human origin were implanted into the left knee joint of mice with severe combined immunodeficiency (SCID), and the joints were analysed histologically after 7 days. In addition, a time course study, including non-invasive monitoring by serological parameters (human IgM, IgG, and IL-6) and Tc-99m-scintigraphy, was performed for up to 4 weeks on RA-SM recipients. All tissue implants induced transient exudative joint inflammation while RA-SM initiated a characteristic arthritis with pannus tissue of high cellular density, erosion, multinuclear giant cells, lining cell hyperplasia, fibroblast-like cell layers, chondroideal metaplasia, and fibrin deposits. Significantly elevated levels of human immunoglobulin and characteristic signs of chronic inflammation persisted for more than 4 weeks. We conclude that the hu/mu SCID arthritis with RA-SM implants comprises features of non-specific inflammation which is also transiently seen with control tissues but develops characteristic features of chronic RA-like synovitis thereafter. | |
| 7561062 | Structural restriction in the heavy chain CDR3 of human rheumatoid factors. | 1995 Oct 1 | We have compared the variable regions of 14 new IgM rheumatoid factors (RFs), produced in healthy human immunized donors (HIDs) with RFs originating from patients with rheumatoid arthritis (RA) and monoclonal Ig RFs (paraproteins or M-components, MC). Two groups with very restricted variable region structures were found. Twelve RFs (3 HID, 3 MC, and 6 RA) encoded by variable heavy (VH) chain germ-line genes with closest homology to DP-10 co-express the Kv325 variable light (VL) chain germ-line gene. These RFs have a remarkable restriction in the length (12-14 amino acids) and structure of the CDRH3. One HID RF has a CDRH3 only two amino acids different from the CDRH3 of a MC RF. Two sets of clonally related RFs, one from an RA patient and one from an HID, have CDRH3s that differ by only three amino acids. Five RFs (3 HID, 1 MC, and 1 RA) encoded by VH germ-line gene segments with closest homology to DP-54 all use the Kv328 VL germ-line gene combined to J kappa 1. Four are rearranged to the D21/9 D segment in the same reading frame, with CDRH3s of 16 to 17 amino acids. Three RFs (1 HID, 1 RA, and 1 MC) have CDRH3s differing by only three amino acids. The highly homologous V-regions in RFs from these two groups imply an initial selection to very similar, if not identical, epitopes. However, it remains to be seen whether somatic hypermutation alters the fine specificity of these autoantibodies. | |
| 8923359 | Is continuous intranasal salmon calcitonin effective in treating axial bone loss in patien | 1996 Nov | OBJECTIVE: To investigate the efficacy of intranasal salmon calcitonin (sCT) in treating axial bone loss in patients with rheumatoid arthritis (RA) taking low dose glucocorticoids. METHODS: In this open, multicenter study 32 women with RA were treated one year with sCT 100 IU/day and calcium (Ca) 500 mg/day; 31 women were treated with Ca alone. Bone mineral density (BMD) was measured at the lumbar spine and proximal femur (femoral neck, Ward's triangle, trochanter) before sCT therapy and again after 6 and 12 months. RESULTS: Among valid completers treated with sCT and Ca (n = 26), the mean BMD increased at the lumbar spine (L1-L4), femoral neck, and Ward's triangle. In contrast, valid completers treated with Ca (n = 23) showed bone loss at the spine (L1-L4), femoral neck, Ward's triangle, and trochanter area. The differences of the changes in BMD were statistically significant between these groups at the femoral neck, Ward's triangle, and trochanter. There were no significant differences between groups in bone loss over 12 months at the lumbar spine (L1-L4), although analysis of the upper segment (L1-L2) suggested some possible benefit of sCT. CONCLUSION: Intranasal sCT (100 IU/day) appears to have beneficial effects on bone loss at the proximal femur in patients with active RA treated with low dose glucocorticoids for 12 months; longer studies are needed to exclude transient bone remodelling effects. | |
| 8833044 | Prognostic implications of HLA genotyping in the early assessment of patients with rheumat | 1996 Mar | Current methods and approaches for the use of HLA markers in the assessment of rheumatoid arthritis (RA) are not optimal. Improved strategies for application of HLA susceptibility genetic typing in patients were evaluated and a new system for rapid determination of these RA susceptibility alleles was developed. Retrospective data summarizing the prevalence of HLA susceptibility alleles in patients with distinct clinical outcomes was analyzed to estimate the sensitivity and specificity of HLA genetic testing as a prognostic marker for erosive disease. A rapid allele specific DNA hybridization assay was performed on an automated instrument using a solid phase nonradioactive hybridization and detection system. Depending on the patient population being tested, from 70-80 percent of patients with progressive erosive disease carry one or more of the DR4 cluster of RA susceptibility genes (DRB1*0401, 0404, 0405). Sensitivity is increased by including other shared epitope positive alleles, but at the expense of specificity. The rapid automated genetic testing system correctly identified each of more than 200 samples tested, with no false positives. HLA genetic testing for RA susceptibility alleles can be performed rapidly and accurately. Prognosis for erosive disease can be facilitated in the patient with early pre-erosive RA using HLA testing in combination with other clinical assessment variables. | |
| 1596703 | A preliminary study on the effect of alpha-interferon treatment on the joint inflammation | 1992 Jun | A 12-week, double-blind controlled study comparing low dose alpha-interferon (5 x 10(5) iu, twice a week) and placebo was carried out to determine whether this drug has an immunomodulatory effect in rheumatoid arthritis. There were statistically significant improvements in the patients' joint score, C-reactive protein value and platelet count, without any side effects. Interferon-alpha caused an increase of serum calcium and a decrease of alkaline phosphatase. Thus, alpha-interferon requires further investigation as a possible additional useful treatment for rheumatoid arthritis. | |
| 8822752 | Scintigraphic evaluation of the severity of inflammation of the joints with 99TCm-HIG in r | 1996 Jun | A prospective study was carried out to determine the usefulness of 99TCm-human immunoglobulin G (HIG) scintigraphy in the assessment of the severity of joint inflammation. Twenty-four patients with rheumatoid arthritis were studied. The presence or absence of pain and/or swelling was evaluated in 34 joints and a clinical index taking into account the surface area of each joint was calculated. We measured the following biological markers of inflammation activity: erythrocyte sedimentation rate, C-reactive protein, haemoglobin, platelet count, serum levels of IL-6, TNF-alpha and soluble receptors of IL-2. Scintigraphic was performed 4 h after the injection of 740 MBq 99Tcm-HIG. The scans were evaluated by visual and quantitative analysis and the scores in each joint were weighted for joint size. Pathological uptake of the radiopharmaceutical was noted in 46% (24/52) of joints evaluated as painful, 89% (146/164) of swollen joints and 94% (78/83) of both painful and swollen joints. Both the visual and the quantitative scintigraphic indices correlated significantly with the clinical index, the number of painful joints, the number of swollen joints and several biological markers of inflammation. A very high correlation was also found between the visual and the quantitative scintigraphic indices (r = 0.91, P < 0.0001). In conclusion, 99Tcm-HIG scintigraphy is an objective test to detect synovitis and to assess the severity of inflammation. A careful visual analysis of scans is good enough for routine evaluations and computer quantitative analysis should be used when more accurate intra-individual variation is required. | |
| 7674230 | Effects of low dose corticosteroids on the bone mineral density of patients with rheumatoi | 1995 Jun | OBJECTIVE: To assess the effect of low doses of corticosteriods on the bone mineral density (BMD) of patients with rheumatoid arthritis (RA). METHODS: A cross sectional study of BMD as measured by dual photon x-ray of the femoral neck and lumbar spine (lateral view) in 139 patients with RA followed in a university setting. RESULTS: The mean daily dose of prednisone taken by the study group was 4.15 mg/day. Patients receiving daily doses of prednisone between 1 to 4 mg/day had similar BMD to patients who were not receiving corticosteroids, but patients taking 5-9 mg/day and those taking > 10 mg/day had significantly lower BMD of the lumbar spine (84.28 and 80.51% of controls, respectively) than patients who received 1-4 mg/day (99.16% of controls). The effect of corticosteroids remained significant when other risk factors such as disease severity, disease duration, functional class, and activity level were controlled for. No significant relationship between prednisone dose and BMD of the femoral neck was seen at the low doses studied. CONCLUSION: Low dose corticosteroid use has a significant effect on BMD of the lumbar spine. | |
| 7824835 | Soluble interleukin-2 receptor in sera and synovial fluids of rheumatoid patients: correla | 1994 | The measurement of serum soluble interleukin-2 receptor (sIL-2R), a sensitive marker of lymphocyte activation, has been proposed as an indicator of disease activity and "outcome" in patients with inflammatory diseases characterized by the activation of immune cells. Serum sIL-2R levels have been reported higher in rheumatoid patients than in controls. Using an enzyme-linked immunoabsorbent assay (ELISA), we evaluated soluble IL-2R levels in the serum of 34 patients with RA and in the synovial fluid of 25 of these patients and we compared it with levels found in the serum of 13 healthy controls. Serum sIL-2R levels were significantly elevated in RA patients compared with the healthy age-matched control group (P < 0.005). The mean level of soluble IL-2R in synovial fluids was significantly higher than the mean sera levels in RA patients (P < 0.0001). Moreover, we examined the correlation between serum and synovial fluid sIL-2R levels and disease activity measures. Serum sIL-2R correlated only with ESR (P < 0.04). The synovial fluid sIL-2R correlated with ESR (P < 0.02) and a visual analogue scale (VAS) pain score (P < 0.04). Both serum and synovial fluid sIL-2R levels correlated with the chronic arthritis systemic index (CASI; P < 0.04 and P < 0.005, respectively). Our data suggested that in RA the measurement of sIL-2R may certainly mirror the degree of chronic inflammation and the continuous activation of the immune cells in the joint, although the role of this molecule in the immune response is still unclear. | |
| 8722204 | Autoimmune connective tissue disease, chronic polyarthritides and B cell expansion: risks | 1996 Jan | Several autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), are characterized by B cell hyperactivity, polyclonal activation, and autoantibody synthesis. Overt B cell clonal expansion occurs in a minority of the patients, while at the tissue level clonotypic B cells may be more easily detected in the majority of patients. The data available suggests that antigen-driven B cell expansion, eventually leading to somatic mutation and transformation, is the main event. Immunosuppressive drugs known to increase chromosomal damage and to lead to earlier transformation should therefore be avoided, unless strictly necessary to preserve vital organ functioning. New immunosuppressive drugs such as methotrexate, cyclosporine A, and Rapamycin are promising for they seem to offer effective control of disease-related organ damage with acceptable side effects. The B cell lymphoproliferative diseases occurring under treatment seem to remit spontaneously after prompt drug withdrawal. Close surveillance, employing new techniques capable of detecting early B or T cell clonal expansion, may allow better monitoring of possible complications. Biological agents such as alpha-interferon and monoclonal antibodies (which are directed against specific immunological mediators and thus target-selected steps of the immune-inflammatory process) have opened promising new research topics in all these diseases. | |
| 8712874 | Cervical spine surgery in patients with rheumatoid arthritis: an appraisal. | 1996 Feb | OBJECTIVES: To review the outcome of surgery undertaken to stabilise the neck in patients with rheumatoid arthritis performed over a five year period, to compare the results with those of previous reports, and to identify factors that may predict surgical outcome. METHODS: Outcome was assessed at time of discharge from hospital after surgery by review of patients' notes, and at follow up by patient interview, clinical examination, anonymous questionnaire, and cervical spine radiograph. The Ranawat classification of neurological impairment and Steinbrocker functional classification were used. RESULTS: Thirty nine patients underwent 44 procedures; 28 patients were available for review after a mean period of 29.8 months (range 12-65 months). Fourteen patients had preoperative neurological impairment and were available for follow up; 13 returned the questionnaire. Four (29%) had improved Ranawat class, nine were unchanged, and one had deteriorated. Nine (69%) reported a subjective improvement in neurological symptoms by questionnaire, even though the Ranawat class was unchanged in five. Twenty five of the patients reviewed had pain before operation; 21 returned the questionnaire. Pain relief was reported by direct questioning and questionnaire in 76% and 67% of patients, respectively. Overall, 67% felt that surgery had been successful. Surgery was more successful in producing symptomatic relief in patients with neck or radicular pain than in those with neurological deficit, but did prevent progression of neurological symptoms. CONCLUSIONS: Our results are similar to those from other centres. Overall patient satisfaction with surgery was good. Surgery was more likely to produce symptomatic relief in patients with neck or radicular pain before operation than in those with neurological deficit. The greater subjective improvement in neurological symptoms as judged by questionnaire probably reflects the relative insensitivity of the Ranawat classification in detecting change in neurological status; previous reports of poor outcome for patients with neurological symptoms who undergo surgery may in part be a reflection of the insensitivity of this method of assessment. No clear factors emerged which allowed prediction of those patients at greatest risk of operative mortality. In particular, an increased risk of neurological compromise appeared to confer no additional risk of immediate perioperative death. Our data support the suggestion that early surgery to correct symptomatic atlantoaxial subluxation may prevent progression of instability. | |
| 1583050 | Arthroplasty of the first metatarsophalangeal joint with a double-stem silicone implant. R | 1992 Apr | Sixty-six patients who had a total of eighty-six double-stem silicone implants in the first metatarsophalangeal joint were followed prospectively for an average of 5.8 years (range, two to fifteen years). There were two groups of patients: thirty-four patients (thirty-seven implants) who had degenerative joint disease (including those who had hallux rigidus or in whom a previous operation on a bunion had failed) and thirty-two patients (forty-nine implants) who had rheumatoid arthritis. The implants were used only if the patient was a candidate for an excisional arthroplasty or an arthrodesis; they were not used in patients who wished to maintain or adopt very active use of the foot (such as in running, jogging, and tennis) or to wear very high heels. Twenty-eight (82 per cent) of the thirty-four patients in the first group were completely satisfied and three (9 per cent) were somewhat satisfied. However, three patients (9 per cent), all of whom had had a failed bunionectomy, were dissatisfied; the ages of these three patients were less than the average age of all patients in the first group. Radiographs showed a fracture in three implants, but the patients had a good clinical result and an additional operation was not warranted. Twenty-seven (84 per cent) of the thirty-two patients in the second group were completely satisfied, four (13 per cent) were somewhat satisfied, and one (3 per cent) was dissatisfied. Radiographs showed a fracture in five implants. Four of the implants caused no symptoms, and the result was good; the fifth one was fragmented and was removed because of symptoms. Radiographs showed radiolucent areas around the implant and hypertrophic changes in many patients. There was no evidence of synovitis, such as that caused by silicone, either clinically or radiographically. We found that the double-stem silicone implant was effective in reconstructing the first metatarsophalangeal joint but emphasize our belief that it should be used only in carefully selected patients. | |
| 8428242 | Unusual DQA-DR haplotypes in rheumatoid vasculitis. | 1993 Feb | DQA and DQB variants and HLA haplotypes were defined in Caucasian subjects with rheumatoid arthritis (RA), in a rheumatoid subset characterized clinically by extra-articular features of major vasculitis, and in controls. DQ variants were defined using a panel of sequence specific oligonucleotide probes. In RA subjects without extra-articular features the frequency of DQB*0301 was significantly increased but this was secondary to the main association with DR4. In rheumatoid vasculitis by contrast, DQB*0302 rather than DQB*0301 was increased in frequency, in addition to an increase of C4A null alleles. Family studies showed that DR4 negative haplotypes had an increased frequency of unusual DR-DQA combinations as compared to other rheumatoid subsets. These findings are in keeping with the concept that genes within the MHC other than DR4 have a disease-modifying role in rheumatoid subsets. HLA haplotypes were defined in a family where the proband has RA and Felty's syndrome and an affected sister has rheumatoid vasculitis. These siblings share a DR4 bearing haplotype typing for DQB*0301, and the sister with rheumatoid vasculitis has a DR4 negative haplotype carrying a C4A null allele and an unusual DR-DQA combination. | |
| 7747149 | Changes in laboratory variables in rheumatoid arthritis patients during a trial of fasting | 1995 | We have previously reported that significant improvement may be obtained in rheumatoid arthritis patients by fasting followed by a vegetarian diet for one year. The present study was carried out to examine to what extent biochemical and immunological variables changed during the clinical trial of fasting and vegetarian diet. For the patients who were randomised to the vegetarian diet there was a significant decrease in platelet count, leukocyte count, calprotectin, total IgG, IgM rheumatoid factor (RF), C3-activation products, and the complement components C3 and C4 after one month of treatment. None of the measured parameters changed significantly during this period in the group of omnivores. The course of 14 of 15 measured variables favored the vegetarians compared with the omnivores, but the difference was only significant for leukocyte count, IgM RF, and the complement components C3 and C4. Most of the laboratory variables declined considerably in the vegetarians who improved according to clinical variables, indicating a substantial reduction in inflammatory activity. The leukocyte count, however, decreased in the vegetarians irrespective of the clinical results. Thus, the decline in leukocyte count may be attributed to vegetarian diet per se and not to the reduction in disease activity. The results of the present study are in accordance with the findings from the clinical trial, namely that dietary treatment can reduce the disease activity in some patients with rheumatoid arthritis. |