Browse

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

ID PMID Title PublicationDate abstract
11056671 IgVH genes from different anatomical regions, with different histopathological patterns, o 2000 In the present study 55 IgVH genes amplified from three different anatomical regions of a rheumatoid arthritis (RA) patient were analyzed, adding further information on synovial B-cell maturation and recirculation in RA. This analysis demonstrated somatically mutated IgVh genes in all regions studied, with amino acid deletions and mixed IgVh molecules, suggesting the existence of a novel pathway to generate (auto) antibody specificities. Comparison of amino acid sequences of amplified genes that belong to the VH1 family (with predominantly the same germline counterpart) exhibited strong homology, indicating an apparently conserved mutational pattern. This suggests that the number of antigens that activate B cells in different locations is restricted. The most striking result was the finding of clonally related sequences in different anatomical regions, indicating a recirculation of activated B cells between the different affected joints.
10941315 [The non-recommendations in the treatment of osteoarthritis and rheumatoid arthritis, or w 2000 May The speed with which the phrase "Evidence-Based Medicine" has entered our language has been astonishing. Virtually all medical areas are concerned, but it probably applies best when clearcut diagnosis can be made or when mortality or well-defined morbidity are the outcomes, two conditions not really frequently encountered in rheumatology. We will discuss why rheumatology is probably not ready yet for the concept and will systematically review why "Evidence-Based Medicine" could in fact be "evidence-biased medicine". We will emphasize why evidence-based medicine can not replace the personal experience and knowledge of patients, two major corner-stones in the clinician's daily work, but should simply be an access to scientific data for the benefit of both patient and physician.
9989846 Subchondral acute inflammation in severe arthritis: a sterile osteomyelitis? 1999 Feb Although arthritis is often associated with synovial inflammation, the osseous changes in inflammatory and degenerative arthritis are principally reactive, and typically lack an acute inflammatory component. We have recently encountered several osteoarticular specimens removed at the time of large joint arthroplasty that have shown a distinctive pattern of subchondral acute inflammation (SCAI) resembling acute bacterial osteomyelitis. These microscopic findings heretofore have not been recognized as a component of the histopathology of arthritis. To determine the frequency of SCAI, we examined slides (mean four per case) from 164 hip arthroplasties performed at one of our institutions in a single year. A total of 10 cases of SCAI, including the 4 original examples (2 humeral head specimens, 2 femoral head specimens) and 6 identified from the slide review are described in this report. Eight patients were female and two were male (ages 54-86 years, mean 70, median 70). All had severe degenerative joint disease, six had rheumatoid arthritis, and three had osteonecrosis. In none was there a clinical or intraoperative suspicion of infection. Cultures of joint fluid or bone were not performed. In all cases, the inflammation was subchondral (within 1.0 cm of the joint surface), and it was frequently associated with subchondral cysts. In osteonecrotic foci, the suppurative inflammation was diffuse within the marrow space, whereas in viable bone it was nodular and vaguely granulomatous. Special stains for organisms were negative. None of the patients was treated with long-term IV antibiotics. There has been no septic loosening of the prostheses at follow-up intervals ranging from 5 to 36 months (mean: 17 months). Our observations, to the best of our knowledge, are novel. Although we cannot definitively exclude bacterial infection as a cause of SCAI, the histologic and clinical features suggest that SCAI likely represents a noninfectious sterile form of inflammation. Subchondral acute inflammation is possibly secondary to synovial fluid insudation into subchondral cancellous bone in the setting of severe osteoarthritis and/or rheumatoid arthritis.
9491678 Rheumatoid arthritis--current trends in management. 1997 Aug RA is a chronic progressive polyarthritis associated with substantial disability. The current treatment protocols envisage early use of DMARDs before erosions develop. Patient education and increased physician awareness are the need of the day in order to minimize the morbidity and mortality associated with this crippling disease.
11820149 [Genetic background of rheumatoid arthritis in connection with a family tree]. 2001 Dec 16 Authors present a rare history of a family with accumulation of autoimmune diseases. From eight siblings four had rheumatoid arthritis, one systemic lupus erythematodes, one primary Sjögren syndrome, and one Reiter disease. Interestingly, neither the parents nor the offsprings were affected. Because of the possible genetic background, the authors performed HLA serologic and DNA investigations in nine members of the family. The results showed, in agreement with data from the literature, the accumulation of HLA-DQ7 (DQB1*0301), DR4, B27 and DR6 (DR13) risk factors. This observation confirms, that the clinical and immunogenetic features are different in familiar and sporadic forms of rheumatoid arthritis. Authors summarize the genetic background of rheumatoid arthritis in connection with this family tree.
11318599 Mutational analysis of immunoglobulin germline derived Vlambda4A light chains in rheumatoi 2001 May In order to better characterize the expression of a family of light chains previously expressed in IgM rheumatoid factors, we studied the usage and somatic mutational pattern of the Vlambda4A light chain gene in rheumatoid arthritis (RA) patients. We sequenced 11 different transcripts of Vlambda4A from the synovial tissue of three different RA patients. For comparison, we found 8 rearranged transcripts of Vlambda4A from 4 normal peripheral blood lymphocyte libraries and 1 rearranged transcript from a non-RA con-A-resistant hybridoma in GenBank. A previously undescribed polymorphism of Vlambda4A was noted. Furthermore, conserved replacement mutations in the complementary determining regions, common silent mutations around these replacement mutations, and two subsets of mutated sequences were detected in multiple RA patients. These mutation patterns also correlated with observed consistencies in the rearrangements of the Vlambda4A/Jlambda junction. These data suggest that there is clonal expansion of Vlambda4A light chains in the RA synovium in response to a RA-specific antigen or as the result of an idiotypic response in RA.
11783141 [Study on relationship between two different syndromes and three soluble cytokine receptor 1999 Dec OBJECTIVE: To study the relationship between two different Syndromes (Cold-Damp Syndrome and Damp-Heat Syndrome) and three soluble cytokine receptors (sCKR, soluble interleukin-2 receptor, sIL-2R, soluble interleukin-6 receptor, sIL-6R, soluble tumor necrosis factor receptor 1, sTNFR1) in rheumatoid arthritis (RA). METHODS: The serum levels of three soluble receptors were measured by ELISA in patients with RA. RESULTS: The serum levels of 3 sCKR were significantly elevated in RA patients compared to healthy controls and obviously lowered after treatment (P < 0.01). The level of sIL-2R was significantly higher in Cold-Damp Syndrome than that in Damp-Heat Syndrome (P < 0.01), but serum sTNFR1 was significantly higher in Damp-Heat Syndrome than that in Cold-Damp Syndrome, there was no obvious difference between sIL-6R of two Syndromes. CONCLUSION: The high serum sIL-2R and low sTNFR1 might be a criterion of Cold-Damp Syndrome, but the high sTNFR1 and low sIL-2R might be a criterion of Damp-Heat Syndrome, these criteria reflected some states of different functions in immune system in patients with RA.
11552899 Chronic use of non-steroidal anti-inflammatory drugs does not alter colonic mucosa of pati 2001 Sep BACKGROUND: Several types of colitis can be NSAID-induced, but whether chronic use of NSAIDs alters colonic mucosa in patients without diarrhoea is not known. PATIENTS AND METHODS: Biopsy specimens of rectal mucosa were taken in six patients with rheumatoid arthritis without diarrhoea receiving NSAIDs (group 1, n=6). Patients with rheumatoid arthritis without diarrhoea not receiving NSAIDs (group 2, n=9), and patients undergoing surveillance colonoscopy (group 3, n=23) served as controls. In all patients from the three study groups, intraepithelial lymphocyte count and apoptotic cell count were assessed, and sub-epithelial collagen band thickness was measured. Leucocyte population of lamina propria was evaluated semi-quantitatively. HLA-DR and CD25 expression of mucosal cells was appreciated by immunohistochemistry. RESULTS: Intraepithelial lymphocyte count was in the normal range in all three group patients, and not statistically different between groups. Apoptotic epithelial cell count was not different between groups. Sub-epithelial collagen band thickness was normal in all the patients. No patient had a marked infiltration of lamina propria by leucocytes, and HLA-DR and CD25 were normally expressed in all patients. CONCLUSION: These results from a small sample of patients suggest that patients without diarrhoea receiving NSAIDs on a long-term basis do not develop microscopic or inflammatory colitis.
11177772 Can we induce tolerance in rheumatoid arthritis? 2001 Feb Oral tolerance (OT) has worked well in numerous laboratory animal models of autoimmune diseases. Humans have been orally tolerized to keyhole limpet hemocyanin (KLH); patients with systemic sclerosis (SSc, scleroderma) have been orally tolerized to oral type I collagen (CI). However, clinical trials of oral type II collagen (CII) therapy in rheumatoid arthritis (RA) have had mixed results. Clinical studies show that compounds (such as nonsteroidal antiinflammatory drugs and prednisone) that inhibit generation of PGE(2) block OT induction. In murine OT models, the PGE(1) analog, misoprostol, reverses the NSAID OT block. These animal studies suggest that OT to CII or other antigens in patients with RA should be inducible if measures are taken to maintain normal prostaglandin function in the gut- associated lymphoid tissue (GALT). A clinical trial is underway in patients with RA to assess whether withholding NSAIDs and prednisone will allow OT to to be induced, and whether oral CII has meaningful clinical efficacy in this disease.
10951406 Rheumatoid arthritis synovial macrophage-osteoclast differentiation is osteoprotegerin lig 2000 Sep Osteoprotegerin ligand (OPGL) is a newly discovered molecule which is essential for osteoclast differentiation. Both OPGL and its soluble decoy receptor, osteoprotegerin (OPG), which inhibits osteoclast formation, are known to be produced by osteoblasts and inflammatory cells found in the rheumatoid arthritis (RA) synovium. In this study, RA synovial macrophages were incubated in the presence or absence of OPGL, macrophage-colony stimulating factor (M-CSF), and dexamethasone for various time points. The results indicated that osteoclast formation from RA synovial macrophages is OPGL-dependent and that OPGL and M-CSF are the only humoral factors required for RA synovial macrophage-osteoclast differentiation. OPG was found to inhibit osteoclast formation by RA synovial macrophages in a dose-dependent manner. This study has shown that macrophages isolated from the synovium of RA patients are capable of differentiating into osteoclastic bone-resorbing cells; this process is OPGL- and M-CSF-dependent and is modulated by corticosteroids. Cellular (T and B cells, dendritic cells) and humoral factors in RA synovium and bone may influence osteoclast formation and bone resorption by controlling OPGL/OPG production.
10546073 The electroneurophysiological findings in rheumatoid arthritis patients. 1999 Oct In rheumatoid arthritis (RA), vasculitis is a serious complication usually found in patients with long-standing erosive nodular seropositive disease. One clinical hallmark of this systemic arteritis is the appearance of neurological findings. However, it is often difficult to diagnose these slight or early neuropathies and the study of the peripheral neuromuscular system is often made difficult by symptoms resulting from pain in the joints and limitations of movement. It is nevertheless often possible by means of electroneuromyography to show objectively the existence and distribution of even subclinical neuropathies. In order to evaluate the neurophysiological functions of RA patients by means of the peripheral nerve conduction and somatosensorial evoked potential studies, 33 RA patients and 20 healthy controls were included in this study. Two (6%) patients were found to have carpal tunnel syndrome, while 6 (18%) patients had mononeuritis multiplex. Delayed N12, N13, N1 and P1 latencies were detected in 6 (18%) of 33 RA patients suggesting central nervous system involvement with intact peripheral nervous system. Our results confirm earlier observations that symptoms of neuropathy are fairly common in cases of RA without there being any clear correlation with any clinical variable. By means of electroneurophysiological studies, it is to evaluate the integrity of the peripheral nerve, the spine and the central pathways. Besides enabling to detect early subclinical involvement of the peripheral nervous system in RA, SEPs should also be used for the evaluation of subclinical myelopathy due to atlantoaxial subluxation or vasculitis. The inclusion of an electroneurophysiologic examination of the RA patients is recommended in routine diagnostic procedure.
9549392 [Fever of unknown origin in rheumatology]. 1998 Jan Fever occurs frequently in several rheumatic disorders, and remains a diagnostic and therapeutic challenge to the rheumatologist in spite of the great advances made in the fields of medical diagnosis and technology. It can be the initial symptom of a rheumatic disease, but it can also be the expression of a disease flare, of an infectious complication, of a secondary neoplasm or be of iatrogenic origin. The pathogenesis of fever in rheumatic diseases is still quite unclear; however, recently IL-1, IL-6 and other endogenous pyrogens, such as Tumor necrosis factor, have been shown to play a pivotal role in causing pyrexia during inflammatory conditions. In the presence of longstanding fever of unknown origin, it is mandatory to carry out a number of selected appropriate examinations with the patient's informed consent. The aim of this study was to review the frequency and the characteristics of fever at the onset and in the course of a number of rheumatic diseases, such as chronic inflammatory arthropathies, connective tissue diseases, reactive arthritis and dysmetabolic arthropathies. Finally, we have reviewed the features of fever during arthritis complicating non-rheumatic diseases and during adverse reactions related to drugs that are widely prescribed for the treatment of rheumatic disorders.
10773796 Hard metal alveolitis accompanied by rheumatoid arthritis. 2000 Hard metal lung diseases (HML) are rare, and complex to diagnose. We describe the case of a patient with allergic alveolitis accompanied by rheumatoid arthritis. A sharpener of hard metal by trade, our patient was a 45-year-old, nonsmoking Caucasian female who experienced symptoms of cough and phlegm, and dyspnea on exertion. Preliminary lung findings were inspiratory rales in both basal areas, decreased diffusion capacity and a radiological picture resembling sarcoidosis. A high-resolution computed tomography scan indicated patchy alveolitis as well. An open lung biopsy revealed non-necrotizing granulomas consisting of epitheloid cells and surrounded by lymphocytes, plasma cells and a few eosinophils. These cells also occupied the thickened alveolar interstitium. Macrophages in the alveolar spaces, some of them multinuclear, contained dust particles. Hard metal alveolitis is clinically well known and, in this patient, has been described histologically. After the patient had quit working with hard metal and following corticosteroid therapy, pulmonary symptoms and signs were relieved. During this recovery period, however, she contracted rheumatoid arthritis.
11522079 Bilateral peroneal nerve palsy after simultaneous bilateral total knee arthroplasty. Repor 2001 Jul In this study, we report on a 46-year-old female patient with bilateral severe gonarthrosis due to rheumatoid arthritis. Simultaneous bilateral cemented total knee arthroplasty was performed. Bilateral common peroneal nerve palsy was observed on the second postoperative day. The electromyographic diagnosis was "bilateral axonotmesis". Complete clinical and electromyographic motor recoveries were seen on both sides within 6 months postoperatively. The sensorial deficit was still present on one side at 2 years postoperatively. Preoperative severe flexion contracture and epidural anesthesia were assumed as the risk factors for the development of the nerve palsy in this patient.
10920690 [Rheumatoid vasculitis with multiple intestinal ulcerations: report of a case]. 2000 Jun Rheumatoid vasculitis is a relatively uncommon complication of rheumatoid arthritis (RA). It shows wide variety of extra-articular features including skin and neurologic involvement, but rarely shows gastrointestinal involvement. We describe a 79-old-man of rheumatoid vasculitis manifesting as small bowel multiple ulcerations accompanied by perforation of the descending colon diverticulum. The patient was admitted to our hospital with rectal bleeding and severe anemia. He had had rheumatoid arthritis for more than 10 years with treatment of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose prednisone. Upper endoscopy or colonoscopy revealed no evidence of bleeding. Suddenly he developed cramping abdominal pain, and emergency operation was performed. Segments of the descending colon and small bowel were resected to reveal perforation of the descending diverticulum and severe multiple ulcer of small bowel. The pathological examination showed multiple ulcerations of the small intestine was caused by vasculitis.
10857786 Identification of four new quantitative trait loci regulating arthritis severity and one n 2000 Jun OBJECTIVE: Collagen-induced arthritis (CIA) is a polygenic model of experimentally induced autoimmunity and chronic joint inflammation. This study maps genetic loci that regulate CIA susceptibility in DA/Bkl (DA) and BN/SsNHsd (BN) rats. METHODS: Genome scans covering chromosomes 1-20 and interval mapping techniques using 159 simple sequence-length polymorphism markers were used to identify quantitative trait loci (QTLs) that regulate CIA in (DA x BN)F2 hybrids. Serum antibody titers to type II collagen were determined by enzyme-linked immunosorbent assay. RESULTS: DA rats were high responders to porcine type II collagen (PII) and developed severe CIA (100%). BN rats were low responders to PII and resistant to CIA (0%). BN genes strongly repressed PII-induced CIA. Only 12% of (DA x BN)F1 rats (7 of 60) and 31% of (DA x BN)F2 rats (307 of 1,004) developed CIA. Three new QTLs (Cia11, Cia12, and Cia13) with significant logarithm of odds (LOD) scores of 5.6, 4.6, and 4.5, respectively, plus a suggestive QTL (Cia14*, LOD 3.0) regulating arthritis severity were identified on chromosomes 3, 12, 4, and 19. A new QTL, Ciaa3, associating with anticollagen antibody titer (antibody to PII LOD 6.5; antibody to rat type II collagen LOD 5.2) mapped to chromosome 9. Of 10 CIA QTLs previously identified in (DA x F344) and (DA x ACI) rats, only Cia1 in the major histocompatibility complex and a region coincident to Cia5 on chromosome 10 (LOD >8.0) influenced CIA severity in (DA x BN)F2 rats. CONCLUSION: Since CIA exhibits many of the pathologic features of rheumatoid arthritis, the data indicate that the variety of genetic elements regulating human autoimmune and rheumatic diseases may be much larger and more varied than originally envisioned.
9841702 Immunological studies of the placenta in maternal connective tissue disease. 1999 Jan Maternal connective tissue disease is an important cause of second-trimester fetal loss. In order to assess the pathological changes in the placenta in maternal connective tissue disease, we reviewed the clinical histories and performed histologic and immunofluorescence studies on nine placentas: five from mothers with systemic lupus erythematosus (SLE), two from mothers with mixed connective tissue disease (MCTD), one from a mother with rheumatoid arthritis (RA), and one from a mother without prior known connective tissue disease. Excessive intervillous fibrin deposition and infarction were noted in all cases. Immunofluorescent and immunoperoxidase studies showed deposits of fibrinogen, IgG, IgM, IgA, and complement 3 (C3) localized to the trophoblast basement membrane (TBM). Electron microscopy documented thickening of the trophoblast basal lamina in three SLE placentas examined. The use of immunofluorescence may be enhanced further if antitrophoblast antibodies can be linked to placental compromise.
9692686 Clinical economics review: gastrointestinal complications of non-steroidal anti-inflammato 1998 Feb Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used symptomatic remedies for rheumatic disorders. Their major side-effects involve the gastrointestinal tract and, while the stomach is often the prime focus of adverse reactions, the whole gut may be involved. A number of strategies have been used to reduce both the incidence of side-effects and their economic consequences. Decreased NSAID use can be achieved both by rational prescribing and by active promotion of other, usually non-pharmacological, methods of controlling symptoms. Prescribing NSAIDs based on their cost assumes all have equal efficacy and side-effects, which is demonstrably untrue. Picking the least toxic NSAID is more logical. Most of the larger studies and meta-analyses available concentrate on older NSAIDs and risk overlooking the advantages of newer preparations which have been shown to be cost beneficial by more comprehensive economic analyses. Misoprostol prophylaxis has been the subject of a number of economic evaluations which, until recently, were based on extrapolations rather than clinical data. There are now good clinical data available which show a small but significant reduction in major side-effects at the expense of an increase in minor but unpleasant ones. Proton pump inhibitors appear to offer the same degree of gastroprotection as misoprostol, with the additional benefit of symptom relief. Economic data regarding the costs and benefits of prophylaxis with proton pump inhibitors are not yet available. There is still a need for a more comprehensive evaluation of the benefits of NSAIDs in different clinical situations to balance against the costs of adverse reactions.
11718162 Treatment of rheumatoid arthritis: unknown long-term effects. 2001 Apr (1) Rheumatoid arthritis, a chronic disease, is defined by a set of clinical, radiological and biochemical criteria. The diagnosis is initially uncertain. (2) Many patients have functional disability 10 years after onset, while others may have little or none. (3) The symptomatic and long-term efficacy of physical (nondrug, nonsurgical) therapies is poorly documented. (4) Various surgical approaches may restore a degree of functional capacity. (5) The use of paracetamol, possibly combined with codeine, can avoid recourse to nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs are the best-assessed analgesics in this setting but carry a risk of severe adverse effects. (6) All long term treatments for rheumatoid arthritis carry a risk of severe adverse effects, and their chronic effects are poorly documented. There is no firm evidence that long term treatments reduce the risk of serious disability or death. (7) Methotrexate is the best-tolerated slow-acting antirheumatic in the medium term, despite a risk of hepatic cirrhosis, pulmonary fibrosis and haematological disorders. (8) Hydroxychloroquine and sulfasalazine are less effective. Hydroxychloroquine carries a risk of retinal damage, while sulfasalazine can cause haematological disorders and skin problems. Chloroquine seems to be slightly more effective than hydroxychloroquine, but at the cost of more adverse effects. (9) The adverse effects of D-penicillamine and injectable gold salts often require treatment withdrawal. (10) The risks associated with immunosuppressants such as ciclosporin mean that these agents should not be used for first-line treatment. (11) The place of various combinations of slow-acting antirheumatics remains to be established. (12) Recourse to systemic steroids must be minimised but is sometimes unavoidable. Low doses are usually adequate. (13) Treatment risks in elderly subjects and patients with comorbidity must be taken into account. (14) Women and men of child-bearing potential who have rheumatoid arthritis must be warned about the toxicity of antirheumatic drugs for the fetus and the effects on fertility.
11196679 Mannose binding lectin (MBL) gene mutation is not a risk factor for systemic lupus erythem 2000 Oct Mannose binding lectin (MBL) deficiency may be associated with increased susceptibility to infection and autoimmune disorders, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In the present study, we performed for the first systematic search for mutations in all the four exons of the MBL gene using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) analysis. Of 49 healthy Japanese individuals studied, only the previously reported mutation at the codon 54 (substitution from Gly to Asp; G54D) was identified. The allele frequencies of G54D in 105 healthy Japanese individuals, 95 SLE patients and 59 RA patients, were 0.233, 0.226 and 0.178, respectively, which were not significantly different. In addition, two polymorphisms at positions of -550 and -221 in the promoter region were not associated with SLE and RA. It is unlikely that MBL deficiency plays a major role in the pathogenesis of SLE and RA in Japanese.