Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
7653938 [Lymphomas of the ocular adnexa in Gougerot-Sjögren syndrome. Apropos of 4 cases]. 1995 The risk of malignant B cell lymphoma is increased in Sjögren's syndrome (SS). Orbital localization seems infrequent. We report 4 cases of malignant lymphoma (ML) occurring in 4 women aged 47 to 77 years, with primary SS in 3 cases, located to the conjunctiva in 2 cases, the lacrymal gland in 1 case and the eyelid in 1 case. The interval between the diagnosis of SS and orbital ML varied from 6 months to 15 years. All 4 lymphomas were of the B cell type, low histopathologic grade, with monoclonal gammopathy in 1 case. Extraocular lymphoma was initially present in 1 case. ML remained localized in 2 cases with a follow-up of 4 and 6 years. Two patients treated by excisional biopsy alone are in complete remission 3 and 6 years later. The 2 other patients treated with orbital radiotherapy and chemotherapy died rapidly (transformation into a high grade malignancy in 1 case). We conclude that clinical, immunopathologic features, as well as prognosis and treatment of ocular adnexa ML in SS are similar to those of primary ML without SS.
8835294 Functional analysis of synovial fluid and peripheral blood T cells from patients with rheu 1995 Rheumatoid arthritis is a T cell-mediated autoimmune disease. The lack of knowledge of the involved target antigens severely hampers research on relevant T cells in patients. Here we describe the functional analysis of freshly isolated T cells from the peripheral blood and the site of the lesion (synovial fluid or synovial membrane) of patients with rheumatoid arthritis. Healthy donors and osteoarthritis patients served as controls. Using various polyclonal stimuli, we analyzed CD4+ T cells with respect to proliferation and their ability to produce lymphokines. Our data show that lesion-derived CD4+ T cells of patients with rheumatoid arthritis are severely defective in proliferation and lymphokine (interleukin-2, interleukin-4, tumor necrosis factor-alpha, interferon-gamma) production. This activation defect was most pronounced at lower cell densities and was present in both synovial fluid derived and synovial membrane derived CD4+ T cells of all patients tested. No difference was found between responses of synovial fluid derived CD4+ T cells from osteoarthritis patients and those observed with peripheral blood derived T cells from all groups. The observed defect in lesion-derived CD4+ T cells from rheumatoid arthritis patients was not due to the effect of inflammatory factors in the synovial fluid because preincubation with synovial fluid could not induce a similar defect in control T cells. Together, our data show a rheumatoid arthritis specific, general defect in the activation of lesion-derived CD4+ T cells.
1411790 [Clinical significance of rheumatoid factor--its complement activating property and isotyp 1992 Aug We investigated the relationship between complement-activating properties of rheumatoid factors (RF) and their isotypes. Active and inactive RA patients without extra-articular symptoms (EAS) and those with EAS were studied. Patients with SLE, liver cirrhosis (LC) and normal volunteers were served as controls. Isotype of RF was measured by ELISA and complement activation (CA) of RF was measured by hemolytic assay. The CA values were significantly higher in RA patients with EAS than those in RA patients without EAS and with other diseases. The IgG and IgM-RF values were significantly higher in active RA without EAS than in inactive RA. Positive correlations between IgM-RF values and CA values were observed in RA with or without EAS, SLE and LC. The Sephadex G-200 gel filtration analysis of sera revealed CA in only 19S IgM fraction. Additionally, we purified 19S IgM-RF from sera of RA, SLE and LC patients by affinity chromatography, and found 19S IgM-RF had CA. These data suggest that serum IgM-RF may play a critical role in the pathogenesis of RA, especially in RA with EAS.
1550402 Prevalence of chronic arthritis in four geographical areas of the Scottish Highlands. 1992 Feb A survey of the prevalence of chronic arthritic conditions was carried out on a population of 35,251 patients registered with 29 general practitioners in the highlands of Scotland. Symptomatic osteoarthritis had an overall prevalence of 65 per 1000 but rose from one in 20 of those aged 40-50 years to one quarter of those over 70 years of age. Rheumatoid arthritis was present in 5.5 per 1000 with a two to threefold female preponderance and there was an unexplained threefold difference between the regions with the highest and lowest prevalence. Seronegative arthritides were found in 2.1 per 1000, polymyalgia rheumatica/temporal arteritis in 1.2 per 1000, and gout in 3.4 per 1000. Juvenile chronic arthritis had a prevalence of 0.39 per 1000 (2.0 per 1000 in those aged 15 years and younger) and connective tissue disease 0.45 per 1000. There was considerable variation in the prevalence of inflammatory arthritis throughout the region. The highest prevalence of rheumatoid arthritis was 14.5 per 1000 women in one east coast area and the lowest 5.2 per 1000 women in the west. The difference did not seem to be due to misclassification. A consultant's review of a questionnaire sent to all except those with osteoarthritis changed the proportions of patients who could be confirmed to have the respective inflammatory arthritides (rheumatoid arthritis between 3.4 and 5.0 per 1000, seronegative arthritides 2.0 per 1000, juvenile chronic arthritis 0.52 per 1000), and a third of those diagnosed as having rheumatoid arthritis failed to meet hospital oriented diagnostic criteria.
8671618 Emergence of CD52-, glycosylphosphatidylinositol-anchor-deficient lymphocytes in rheumatoi 1996 Mar CD52 is a glycosylphosphatidyl-inositol (GPI)-linked glycoprotein expressed at high levels on normal T and B lymphocytes and at lower levels on monocytes, while being absent on granulocytes and bone marrow stem cell precursors. The emergence of CD52- lymphocytes of both T and B cell lineages was observed in three out of 25 rheumatoid arthritis patients treated with teh humanized antibody Campath-1H in phase II clinical trial. Whereas the majority of CD52- B cells had disappeared from the peripheral blood by 3 months post-treatment, both CD52- CD4+ and CD8+ T cells persisted in the circulation for at least 20 months. In the two patients that were tested, the GPI-anchored surface molecules CD55 and CD59 were also absent on the CD52- cells, although expression of other cell surface transmembrane, proteins (CD3, CD4 and CD2) was unaffected. The CD52- cells maintained a stable phenotype in vitro despite repeated re-stimulation in culture. Both CD52- and C52+ clones, established from one of the patients, responded to a similar extent to several T cell mitogens, as assessed by proliferation, suggesting that a general defect in expression of GPI-linked molecules does not impair T cell activation. These data show that an immune attack against a GPI-anchored surface molecule can result in the selection of a GPI-anchor-deficient cell population. Despite the persistence of CD52- T cells in the peripheral blood, no adverse reactions associated with the presence of these cells were noted in any of the patients; in fact they responded with longer remission times after Campath-1H treatment than the other patients in the trial.
8325044 Double-blind comparison of etodolac and diclofenac in patients with rheumatoid arthritis. 1993 The efficacy and tolerability of etodolac was compared to diclofenac in a multi-centre, double-blind, randomized parallel group study. Fifty-three patients with rheumatoid arthritis received etodolac (400 mg/day) and 55 patients received diclofenac (150 mg/day) for 12 weeks. Thirty-nine etodolac-treated patients and 44 diclofenac-treated patients completed the study. At the final evaluation, etodolac-treated patients showed significant (p < or = 0.05) improvement for all 4 primary assessments (patients' and physicians' global evaluations, number of tender or painful joints, and number of swollen joints) and 6 of 7 secondary assessments, while diclofenac-treated patients showed significant improvement for 3 primary assessments (patients' and physicians' global evaluations and number of tender joints) and 3 secondary assessments. In the physicians' global assessment, improvement at the final evaluation was indicated for 58% of the etodolac-treated patients and 47% of the diclofenac-treated patients. Both etodolac and diclofenac were well tolerated. As expected for non-steroidal anti-inflammatory drugs, gastrointestinal side-effects were the most common, occurring in 12 patients in each group. There were no significant differences between groups in the incidence of any study event. In conclusion, the results of this study indicate that etodolac is well tolerated and effective in the treatment of rheumatoid arthritis, comparable to diclofenac.
7848316 Reduced red blood cell deformability in patients with rheumatoid vasculitis. Improvement a 1995 Feb OBJECTIVE: To assess red blood cell deformability (RCD) in patients with rheumatoid arthritis (RA) without extraarticular manifestations and in RA with vasculitic complications (RV), and to assess whether in vitro dipyridamole improves RCD. METHODS: An improved filtration technique was used to measure RCD in 15 patients with RA, 18 patients with RV, and 20 age- and sex-matched normal control subjects. Washed erythrocytes suspended in buffer, at 5% hematocrit, were filtered through 4.7 mu Nuclepore Hemafil PC membranes. The initial steady-state relative filtration pressure (iRFP) was used as an index to assess RCD. A lower iRFP value reflects increased deformability, a higher value reflects a decrease. For each sample, 2 cell suspensions were prepared, one blank (control) and one containing 5 microM dipyridamole. RESULTS: The mean iRFP values of cells obtained from patients with RV were significantly higher than those of cells obtained from normal controls. There were no appreciable differences in iRFP between RA patients and normal controls. When the erythrocytes were pretreated in vitro with 5 microM dipyridamole before filtration, their deformability improved markedly (iRFP values were reduced) in all study subjects, compared with untreated cells. CONCLUSION: RCD is reduced in patients with RV, and treatment with dipyridamole may be beneficial if reduced RCD contributes to impaired microvascular perfusion.
1581140 Epidemiology of the rheumatic diseases. 1992 Apr Replication of similar findings in diverse study populations using different study designs provides important evidence for causal inferences regarding risk factors reported in epidemiologic studies. Risk factors for knee osteoarthritis have been substantiated in a number of cross-sectional and longitudinal cohort studies. Longitudinal cohort studies have also added to our understanding of risk factors associated with hip osteoarthritis and hand osteoarthritis. In contrast, studies of hormonal and reproductive factors and the risk of developing rheumatoid arthritis continue to report conflicting results, and the importance of these risk factors remains unresolved. Recent studies suggest that the protective effect is limited only to the development of definite rheumatoid arthritis with a more severe clinical course. Cross-sectional studies of diverse populations show consistent age- and gender-specific differences in the rates of hip fracture among persons of Japanese ancestry and rates among several different groups of whites in the United States. The results of a population-based longitudinal cohort study suggest that women who live in communities where the drinking water has a high content of fluoride have a greater risk of osteoporosis and subsequent fractures than those living in communities with low fluoride in the drinking water. Finally, several recent reports provide additional evidence of the increasing incidence of acute rheumatic fever in the United States and other parts of the world.
8693195 [Changes in thyroid function in systemic lupus erythematosus, progressive systemic scleros 1994 According to frequent thyroid function disorders in systemic connective tissue diseases a group of 380 patients were analysed - 70 with systemic erythematous lupus (SLE), 31 with progressive systemic scleris (PSS) and 270 with rheumatoid arthritis (RA). Thyroxine (T4) and triodothyronine (T3) were measured by radioimmunoassay technique and thyroid stimulating hormone (TSH) chronologically by monoclonal antibody technique and thereafter by fluoroimmunoassay. Thyreopahty was found at 15 patients with SLE (21.43%), 11 patients with PSS (35.48%) and 35 patients with RA (12.54%). Our results pointed out the significant frequency of thyroid function disorders in these diseases and imply the necessity of the routine thyroid function follow up, therefore to take adequate cure in due time.
7686090 In vivo T cell depletion in rheumatoid arthritis is associated with increased in vitro IgM 1993 May T cell depletion has been demonstrated to have therapeutic potential in patients with rheumatoid arthritis and several agents which deplete or inactivate T cells are currently being evaluated in clinical trials. We treated six patients with active rheumatoid arthritis with one such agent, the murine IgG1 anti-CD5 immunoconjugate CD5 Plus, as part of a multicenter trial. Measurement of in vitro synthesis of IgM and IgM-rheumatoid factor by peripheral blood mononuclear cells obtained from patients before, during, and after treatment, was performed using enzyme-linked immunoassays. Subsets of T and B lymphocytes were measured by flow cytometry. Significant T cell depletion was observed on Days 2 and 5 during the treatment period and was associated with increased in vitro rheumatoid factor (RF) production on Days 5 and 8 in 4 of the 5 patients with significant pretreatment levels of RF synthesis. No apparent relationship to serum RF levels or clinical responses was noted. These results implicate a role for T cells in the control of IgM-RF production in patients with rheumatoid arthritis.
1525624 Increased serum concentrations of cartilage oligomeric matrix protein. A prognostic marker 1992 Sep Two cartilage specific macromolecules, cartilage oligomeric matrix protein (COMP) and proteoglycan, were quantified by immunoassay in sera of two groups of patients with rheumatoid arthritis (RA) of recent onset to evaluate the prognostic value of such measurements. Patients with rapidly progressive joint destruction had increased COMP concentrations initially, which subsequently decreased. A group with more benign disease, and less extensive joint damage, had normal COMP levels throughout the study period. Serum concentrations of proteoglycan were normal in both groups. Thus measurement of COMP in serum early in the course of RA holds promise as a prognostic marker for development of joint destruction in this disease.
8426374 Incidence of cancer among patients with rheumatoid arthritis. 1993 Feb 17 BACKGROUND: To evaluate hypotheses about the relationship between immune alterations and cancer, several investigators have determined cancer incidence in groups of patients with rheumatoid arthritis (RA), a chronic autoimmune disease. The primary finding has been an increased risk of hematopoietic cancers. PURPOSE: In this study, we have attempted to refine estimates of the association between RA and subsequent development of specific cancers. METHODS: We investigated site-specific cancer risk associated with RA in a population-based cohort study of 11683 Swedish men and women with a hospital (inpatient) diagnosis of RA. These case patients were identified from 1965 to 1983 and had follow-up through 1984 by computer linkage of the Swedish Hospital Inpatient Register to the National Swedish Cancer Registry (840 case patients with cancer) and the Swedish Registry of Causes of Death. Cancer risk was estimated by standardized incidence ratios (SIRs) for specific cancers. RESULTS: For men and women overall, there were decreased risks for cancers of the colon (SIR = 0.63; 95% confidence interval [CI] = 0.5-0.9), rectum (SIR = 0.72; 95% CI = 0.5-1.1), and stomach (SIR = 0.63; 95% CI = 0.5-0.9) and an increased risk for lymphomas (SIR = 1.98; 95% CI = 1.5-2.6). CONCLUSIONS: The reduced risk for colorectal cancer in patients with RA is consistent with previous studies of RA patients and with reports which state that use of nonsteroidal anti-inflammatory drugs may protect against the development of large bowel cancers. The excess of lymphomas also confirms a number of earlier investigations of RA patients.
7671512 Extramedullary versus intramedullary alignment guides in total knee arthroplasty. 1995 Sep Use of extramedullary and intramedullary guides to prepare the tibia was studied comparatively in 100 consecutive primary total knee arthroplasties done by a single surgeon. Each type of guide was used in 50 consecutive cases, for a total of 100 cases. In all cases, an intramedullary guide was used to prepare the distal femur. Long (hip to ankle) anteroposterior radiographs were taken postoperatively to measure the mechanical angle, tibial component angle, femoral component angle, physiologic valgus angle, and tibiofemoral angle. No significant differences between the extramedullary and intramedullary groups were found; each system allowed satisfactory alignment. It is important for the surgeon to appreciate the benefits and deficiencies of each guide and to use whichever is suited most properly in each particular case.
8623611 [Involvement of the shoulder in rheumatoid arthritis]. 1995 The course of rheumatoid arthritis (R.A.) in the shoulder is evaluated in 100 patients in a retrospective study and in 73 patients in a prospective study. The involvement of the shoulder may occur at an early stage of the disease. However, usually it causes a significant handicap at a later stage. The retrospective study shows that 62% of the patients hospitalized between 1976 and 1992 for R.A. complained of pain, reduction in range of motion and functional disability of one or both shoulders. However, these historic cases cannot be used for a radiological study because the shoulders have been radiographed in 17% of cases only, probably because of the poor possibilities of surgical therapies available at this time. The survey of 72 patients received at the out- patient clinic between september 1992 and december 1993 who had a radiograph of the shoulder is the basis for the description of the progress of the disease. The erosions appear at the border of the cartilage where the synovium is attached and refers mainly to the cephalic articular cartilage. Narrowing of the subacromial space is often present with early appearance of subluxation in the cranial direction. The destruction often prevails in the area of humeral head but cases with predominant global joint space narrowing or with destruction of glenoid labrum and fossa exist as well. Secondary osteoarthritis was often observed. The involvement of the shoulders is not always symmetric. Unilateral involvement has been observed. The different evolutive processes will be illustrated and their frequency evaluated. The forms with predominant cephalic destruction constitute the best indications for total shoulder arthroplasty.
7864690 Increment of CD8S6F1 cells in synovial fluid from patients with rheumatoid arthritis. 1994 Dec OBJECTIVE: To investigate the role of CD8 cell subsets in the pathogenesis of rheumatoid arthritis (RA) and the phenotypes of T cells adherent or non-adherent to the target cells (endothelial cells and synovial cells) pre-treated with IL-1 beta. METHODS: The expression of S6F1 on CD8 cells and that of an activation marker on CD8 cells and CD8 cell subsets was evaluated in specimens of peripheral blood and synovial fluid obtained from 15 patients with RA and 10 with osteoarthritis (OA) using a two- or three-colour immunofluorescence method for analysis. RESULTS: The percentage of CD8S6F1 cells among CD8 cells in synovial fluid was significantly greater than that of peripheral blood. Synovial fluid from RA patients had a greater percentage of CD8S6F1 cells compared with either peripheral blood of matched patients or synovial fluid of OA patients. The percentage of CD8HLA-DR cells in synovial fluid was markedly greater than that in paired samples of peripheral blood in patients with RA. In the CD8S6F1 cells from both groups of patients, synovial fluid showed an increased percentage of HLA-DR cells compared with peripheral blood. Similar results were observed in CD8 cells lacking S6F1 expression (CD8S6F1-) from both groups of patients. There was no significant difference in the percentage of HLA-DR cells between CD8S6F1 and CD8S6F1- cell populations in peripheral blood. In contrast with peripheral blood, in synovial fluid of RA patients the percentage of HLA-DR cells in the CD8S6F1 cell population was markedly greater than that in the CD8S6F1- population. However, the percentage of HLA-DR cells in both cell populations was similar in synovial fluid of OA patients. In both the endothelial and the synovial cell adhesion assays, the percentage of CD8S6F1 among CD8 cells and the mean fluorescence intensity of S6F1 antigen on CD8S6F1 cells were significantly greater in the adherent T cell population than that in the non-adherent T cell population. CONCLUSION: These results suggest that increased expression of S6F1 antigen and the increased percentage of HLA-DR cells on CD8 cells in synovial fluid may be responsible for the migration of these cells into inflamed synovial tissues, and for cellular interactions between these cells and synovial cells or the extracellular matrix.
7732487 [Sleep apnea syndrome in rheumatoid arthritis (RA) patients complicated with cervical and 1995 Feb All-night polysomnographic studies were performed on ten patients (all female) with rheumatoid arthritis complicated with temporomandibular joint destruction and cervical lesions. The mean age of these subjects was 67.5 yrs, ranging from 48-81 yr. They all had some morphologic abnormalities of cervical spines and/or temporomandibular joints. Sleep study revealed that all of them had sleep apnea; five of them were of obstructive type (obstructive group) while the remaining showed central type of sleep apnea (central group) predominantly. There were no statistically significant differences of the levels of apnea index, mean-nadir SO2 and the lowest SO2 between the obstructive group and the central group. No detectable differences of cephalographic measurements and MRI findings existed between the two groups either. In one patient, nasal-CPAP converted central apnea to normal breathing dramatically. Our observations indicate that the cause of central apnea in RA patients with temporomandibular lesions is collapse of upper airway, inducing inhibitory inputs from the mechanoreceptors in that region.
7504021 Differential expression in rheumatoid synovium and synovial fluid of alpha 4 beta 7 integr 1993 Dec 1 T lymphocyte adhesion to vascular endothelium plays an important role in the immunopathogenesis of rheumatoid arthritis. The migration of T lymphocytes into the synovium is mediated by a variety of adhesion molecules, notably the integrins. We have prepared Act I, a murine mAb that identifies a novel integrin termed alpha 4 beta 7. The natural ligands for alpha 4 beta 7 are vascular cell adhesion molecule-1 and fibronectin; both molecules are up-regulated in the rheumatoid synovium. We investigated the expression of alpha 4 beta 7 in the three compartments of rheumatoid arthritis, the peripheral blood, synovial fluid, and synovial membrane, utilizing the FACS and immunoperoxidase microscopy of frozen tissues. The results of our experiments show a striking differential expression of alpha 4 beta 7 integrin in rheumatoid arthritis. Sixty-two percent of synovial membrane T cells expressed high density alpha 4 beta 7, in contrast to only 4.7% of synovial fluid and 9.1% of PBL. These data suggest that the expression of alpha 4 beta 7 integrin may provide a mechanism whereby certain T cells adhere to rheumatoid synovium while others remain in the synovial fluid. The augmented expression of alpha 4 beta 7 in the synovial membrane T cells may contribute to the development and perpetuation of rheumatoid arthritis.
8164222 Unilateral ptosis as an initial manifestation of D-penicillamine induced myasthenia gravis 1993 Sep We describe 2 patients presenting with isolated unilateral ptosis without other signs of cranial or peripheral nerve involvement or sympathetic denervation. Both patients (one case of progressive systemic sclerosis and one of rheumatoid arthritis) were currently taking D-penicillamine. In these cases, the ptosis was reversed a few minutes after a Tensilon test, hallmark of myasthenia gravis. Antibodies to acetylcholine receptors were present. Myasthenia gravis should be suspected with ptosis without other cranial nerve involvement or miosis, even if the ptosis is unilateral. Thus, unilateral ptosis can be the first manifestation of a toxic side reaction to D-penicillamine.
8624624 Quantitative assessment of synovial inflammation by dynamic gadolinium-enhanced magnetic r 1996 Jan The effect of temporary inflammatory suppression on synovial membrane enhancement, as determined by dynamic and static gadolinium-DTPA enhanced magnetic resonance imaging (MRI), was studied. MRI of 18 arthritic knees was performed before and 1, 7, 30 and 180 days after intra-articular methylprednisolone injection until clinical relapse. MRI of another six knees was performed twice within 2-4 days in order to assess interobserver and inter-MRI variation. The rate of early enhancement of the entire synovial membrane of a pre-selected central sagittal slice (REEsyn,tot), determined by dynamic T1-weighted FLASH MRI, decreased in all knees within the first post-treatment week and remained low during remission, although gradually increasing. In cases of clinical relapse, REEsyn,tot increased to pre-treatment levels. The interobserver plus inter-MRI variation was maximally 27%. The predictive values of a REEsyn,tot below/above 1.0%/s were 0.94 and 0.91, respectively, with respect to the absence/presence of clinical synovitis. Evaluation of small synovial areas revealed marked regional heterogeneity. Static spin echo MRI was not informative. The study indicates that the rate of early synovial enhancement reflects synovial inflammatory activity. Subclinical changes may be revealed. Evaluation of large synovial areas increases reproducibility and reduces the effect of regional heterogeneity. Dynamic MRI may prove a clinically useful measure of synovial inflammation.
1374252 Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rhe 1992 May OBJECTIVE: To compare the levels of biogenic amines in the cerebrospinal fluid (CSF) of primary fibromyalgia syndrome (PFS) patients with those in the CSF of controls. METHODS: Metabolites of serotonin, norepinephrine, and dopamine were identified in CSF, using high performance liquid chromatography with coulometric detection. RESULTS: CSF levels of metabolites from all 3 neurotransmitters were lower in PFS patients than in controls. CONCLUSION: A low rate of turnover of several neurotransmitters supports the proposed hypothesis of a metabolic defect in PFS and suggests that the defect occurs at a neuroregulatory level.