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

ID PMID Title PublicationDate abstract
10798093 Progressive pseudorheumatoid arthropathy of childhood. 1999 May Progressive pseudorheumatoid arthropathy of childhood (PPAC) described by Spranger et al is a rare autosomal recessive disorder. An 11 year-old girl was diagnosed as having PPAC at Ege University, Faculty of Medicine, Department of Paediatrics. Her complaints of painful joints, difficulty in walking and joint contractures began at the age of 3 years and she was treated for juvenile rheumatoid arthritis for 8 years. Her symptoms did not respond to nonsteroid anti-inflammatory treatment. During her last hospitalisation period, she was reinvestigated. Radiological examination showed spondyloepiphyseal dysplasia, severe acetabular irregularity and osteoporosis. All the laboratory test results for rheumatoid arthritis were negative. The clinical and radiological findings of the patient are illustrated.
10526489 [Arthritis of the shoulder]. 1999 Sep 1 Diagnosis of shoulder arthritis should situate the precise location (glenohumeral, acromioclavicular, scapulothoracic) and rapidly determine the cause in order to eliminate the possibility of septic arthritis which requires urgent treatment. Good knowledge of shoulder symptomatology is essential. When there is joint effusion, the fluid should be sampled for rapid analysis (cells, crystals, germs), and the work-up for diagnosis must include clinical and laboratory analyses as well as imaging. Causes are especially microcrystallin arthritis (hydroxyapatite rheumatism, chondrocalcinosis, etc.) and inflammatory rheumatism (rheumatoid arthritis, ankylosis spondylitis, etc.). Septic arthritis is much less common but more rapidly destructive, which justifies their consideration whenever suspected. Treatment should be rapidly initiated in acute, particularly septic forms. In other forms, diagnosis guides treatment. Steps should be taken rapidly, both medically and sometimes surgically, to avoid destructive articular and periarticular lesions (rotator cuff).
9831319 Novel pathways for glucocorticoid effects on neutrophils in chronic inflammation. 1998 Oct Neutrophils have been implicated in mediating much of the tissue damage associated with chronic inflammatory diseases such as rheumatoid arthritis, where they are involved in destruction of both cartilage and bone. Glucocorticoids are powerful anti-inflammatory agents, often used in the treatment of this autoimmune disease. They exert significant inhibitory effects on neutrophil activation and functions, such as chemotaxis, adhesion, transmigration, apoptosis, oxidative burst, and phagocytosis. The mechanisms by which glucocorticoids exert these effects on neutrophils are unclear. Evidence from studies of inflammation in human subjects and animal models suggests that annexin-I an endogenous, glucocorticoid-induced protein also known as lipocortin-1, has a pivotal role in modulating neutrophil activation, transmigratory, and phagocytic functions. Furthermore, we present evidence for altered neutrophil functions in rheumatoid arthritis that correspond to a significantly reduced capacity of these cells to bind annexin-I. A proposed novel pathway for glucocorticoid actions on neutrophils involving annexin-I could explain the development of chronic neutrophil activation in diseases such as rheumatoid arthritis.
10756660 [Periungual capillaroscopy in psoriatic arthritis]. 1999 Nov PURPOSE: The aim of the study is the evaluation of the microcirculation trough periungueal capillaroscopy in patients suffering from psoriatic arthritis. MATERIALS AND METHODS: Eighteen patients (mean age 44 years, nine males and nine females) were examined according to the different clinical forms (spondylitic, mutilans, simil-rheumatoid, onyco-arthritis, oligo-articular) of the disease. RESULTS: In most of the patients, the exam showed a reduction in ansas' density and in capillary length and calibre as well as interstitial edema and expansion of the ansa venular portion with coiling and kinking, demonstrating the re-organization of the veins and the neo-angiogenesis. Avascular areas and microaneurysm have been found only in the "mutilans" form. In the "simil-rheumatoid" form, ansa reduced in length and calibre have been observed at capillaroscopy, a pattern different from that reported by others, in rheumatoid arthritis (characterized by thin but lengthened ansa). In the "spondylitic" form, the video-microscopical pattern was negative. CONCLUSIONS: This study is still ongoing in order to evaluate the results in a more representative sample.
11881379 [Humoral immunological aspects of the pathogenesis of rheumatism, nonrheumatic carditis an 2001 Sep The state has been studied of the humoral component of immunological reactivity according to the content of the serumal complement, complement-bounding antibodies, immunoglobulins and immunoglobulin-antibodies of the main classes in the time-related course of rheumatism, nonrheumatic carditis and juvenile rheumatoid arthritis (JRA) in children. Tissue, enzymic, streptococcal antigens have been used together with those of nucleotides, nucleases. The obtained results suggest to us that the humoral component of bodily immunological reactivity has an important part in pathogenesis of the above medical conditions. It can be used in the diagnosis of affections of the heart.
18034514 Could hormones make a difference in the treatment of juvenile rheumatoid arthritis? 2000 Feb Adrenal androgens dehydroepiandrosterone (DHEA; prasterone) and its sulphated form (DHEA-S) are among the most abundant hormonal steroids in men and nonpregnant women. Deficiencies of these adrenal androgens are associated with autoimmune disorders such as rheumatoid arthritis (RA). Recent studies from our laboratory have also identified low levels of adrenal androgens in the serum and synovial fluid of patients with juvenile rheumatoid arthritis (JRA). These findings support and complement those already published for RA and other autoimmune diseases. Because of the paucity of data on the hormonal status of patients with JRA, studies on the relationship between hypoandrogenicity and predisposition to develop JRA, and/or disease progression have not been conducted. In addition, despite the rapid expansion of research in the clinical use of these adrenal androgens in hyperlipidaemia, atherosclerosis, obesity, diabetes mellitus, insulin resistance and hypertension, their potential beneficial effects in JRA/RA have not been fully investigated. In fact, clinical trials of adrenal androgens in RA have only been conducted for the treatment of systemic lupus erythematosus. Further studies using prospective approaches are necessary to provide a unified consensus on the hormonal status of patients with JRA (as well as those with RA). This overview of our knowledge of the putative role(s) of hormones in arthritis will hopefully stimulate researchers in basic science and rheumatologists to synergistically collaborate in the effective translation of such knowledge to new clinical approaches.
9260622 Isolated digital swelling as the initial presentation of juvenile rheumatoid arthritis. 1997 Jul Juvenile rheumatoid arthritis (JRA) is an inflammatory condition that affects children under 16 years of age. The cases of 7 patients with isolated finger swelling as the initial manifestation of JRA are reviewed. In these children, the diagnosis was significantly delayed (t-test, p < .0076) for up to 14 months (mean, 8 months) when compared to a mean of 3.4 months in the JRA patients with a typical onset. Of the patients with the initial presentation of isolated digital swelling, +/7 (57%) had disease that became polyarticular, whereas only 15% of the patients with the initial presentation of large-joint disease experienced progression to polyarticular disease (Fisher's exact test, p < .0307). This presentation of JRA should be recognized so that appropriate management can be instituted promptly.
9425866 Subtalar arthrodesis for subtalar arthritis. 1997 Nov Primary subtalar arthritis is not common except in cases of generalized arthritis such as rheumatoid arthritis. The majority of subtalar arthritis results from intraarticular calcaneal fractures. Arthrodesis seems to be the only way to solve this problem. Thirteen patients (15 feet) were treated with subtalar arthrodesis at KMCH. Preoperative diagnosis included 13 feet with traumatic arthritis secondary to a calcaneal fracture, one foot with rheumatoid arthritis and one foot with primary osteoarthritis. The mean follow up period was 24.9 months. Lateral approach without fibular osteotomy was done with decompression if there was entrapment syndrome and the arthrodesis were accomplished with use of staples for internal fixation. Eleven (85%) of the patients were satisfied with the results. Objectively, the results were excellent after 11 arthrodesis (73%), good or fair after three (20%), and poor after one (7%). There was no nonunion. Complications occurred in 1 patient who developed superficial wound infection, and in 1 patient with staple loosening. Though there was no case of nonunion, the fusion time was rather long. This might have been due to the fixation method because staples can not provide compression force which accelerates union. We believe subtalar arthrodesis is appropriate for isolated subtalar arthritis unless there are associated talonavicular or calcaneocuboid arthritis in which case triple arthrodesis will be more appropriate.
9034294 Myelodysplastic features in juvenile rheumatoid arthritis. 1997 Feb We have attempted to investigate the dysplastic changes in the hematopoietic system associated with juvenile rheumatoid arthritis (JRA) and its relation to disease activity. The peripheral blood smear and bone marrow aspiration samples of 17 JRA patients were investigated and correlations with laboratory parameters of disease activity sought. The age range was 6-16 years and the duration of disease 1.5-108 months. Abnormal finding of the peripheral smear and bone marrow were scored separately. The score of pathological peripheral blood findings correlated significantly with CRP and ferritin (both P <0.05). In the bone marrow specimens marked changes were noted in the myeloid, erythropoietic, and megakaryopoietic series; however, the score of pathological findings did not correlate with laboratory parameters of disease activity (P > 0.05). We suggest that JRA is associated with marked myelodysplastic changes, also manifested in the peripheral blood smear; these changes may well be the consequence of the inflammatory milieu, including cytokines, during active disease.
10332983 Human immunodeficiency virus infection associated arthritis: clinical characteristics. 1999 May OBJECTIVE: To define the frequency and characteristics of human immunodeficiency virus (HIV) associated arthritis. METHODS: A total of 270 patients with HIV infection were prospectively evaluated for the presence of rheumatic complaints. Diagnosis of HIV infection was performed by ELISA and confirmed by Western blot, and all HIV patients were classified according to the US Centers for Disease Control criteria. RESULTS: Twenty-one (7.8%) patients presented with HIV associated arthritis. Other arthritides including HLA-B27 related, such as Reiter's syndrome, psoriatic arthritis, and rheumatoid arthritis, were excluded. Seventeen were men and 4 women, with a mean age of 34.8 years (SD 11.1). Fourteen (66%) were homosexuals, 4 (19%) intravenous drug users, and 3 (14%) heterosexuals. Twelve (57%) were in stage IV, 5 (23%) in stage III, and 4 (9%) in stage II. Ten (47%) patients had oligoarticular involvement, 8 (38%) monoarticular, 2 (9%) asymmetric polyarthritis, and one (4%) symmetric polyarthritis. Rheumatoid factor and HLA-B27 antigen were negative in all (15) patients studied. The mean duration of arthritis was 2 weeks (1-24). No differences in duration of arthritis were found among the different risk factors (p = 0.811), HIV stages (p = 0.205), and type of articular involvement (p = 0.252). There was, however, a trend between the number of involved joints and stages of HIV infection (p = 0.13). CONCLUSION: The pattern of joint involvement of HIV associated arthritis is similar to that of other viral disorders: acute onset, short duration, no recurrences, and no erosive changes.
11708432 Juvenile rheumatoid arthritis-like polyarthritis in Nijmegen breakage syndrome. 2001 Nov Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease (8q21) from the family of the genetically determined chromosomal instability syndromes. The disorder is characterized by microcephaly, growth retardation, immunodeficiency, and high incidence of cancer. Several noninflammatory anomalies of the musculoskeletal system have been described in patients with this syndrome. We describe an Argentinian girl with all the clinical, immunological, and cytogenic characteristics described for NBS plus a juvenile rheumatoid arthritis-like syndrome. To our knowledge this is the first report of a patient with the NBS who presented with a symmetric chronic polyarthritis resembling JRA.
9133930 Persistence of Staphylococcus aureus as detected by polymerase chain reaction in the synov 1997 Feb Septic arthritis commonly occurs in the rheumatoid arthritis population. The diagnosis is frequently delayed and the associated mortality is high. In this brief report, we present a patient with rheumatoid arthritis and prosthetic knee joints who developed septic arthritis and had persisting evidence of Staphylococcus aureus DNA in synovial fluid, from his knees, which was detected by polymerase chain reaction (PCR) and a gene probe. This was detected until 10 weeks of therapy despite adequate antibiotic treatment and a sterile synovial fluid. In the future, it may be found that PCR of the synovial fluid will be a valuable investigation for the diagnosis and management of septic arthritis.
10782854 Bone mineral status in juvenile rheumatoid arthritis. 2000 Apr Osteoporosis can be thought of as a disease of childhood with manifestations in the adult years. One strategy in prevention of osteoporosis is to maximize peak bone mass with interventions focused during the childhood and adolescent years, taking advantage of this unique window of opportunity to maximize bone mass accrual, maximize peak bone mass, and theoretically decrease fracture risk for life. Factors important in the development of peak bone mass in children are reviewed. Studies examining bone metabolism and bone density in children with juvenile rheumatoid arthritis (JRA) are summarized. There is much work to be done before the best treatments for the osteoporosis of JRA are defined. Optimizing calcium intake and physical activity, along with corticosteroid avoidance and control of disease activity, is sound management for children with JRA.
15758488 Animal models of rheumatoid arthritis. 2001 Jun Animal models of arthritis are used to study pathogenesis of disease and to evaluate potential anti-arthritic drugs for clinical use. Therefore morphological similarities to human disease and capacity of the model to predict efficacy in humans are important criteria in model selection. Animal models of rheumatoid arthritis (RA) with a proven track record of predictability for efficacy in humans include: rat adjuvant arthritis, rat type II collagen arthritis, mouse type II collagen arthritis and antigen-induced arthritis in several species. Agents currently in clinical use (or trials) that are active in these models include: corticosteroids, methotrexate, nonsteroidal anti-inflammatory drugs, cyclosporin A, leflunomide interleukin-1 receptor antagonist (IL-1ra) and soluble TNF receptors. For some of these agents, the models also predict that toxicities seen at higher doses for prolonged dosing periods would preclude dosing in humans at levels that might provide disease modifying effects. Data, conduct and features of the various models of these commonly utilized models of RA as well as some transgenic mouse models and less commonly utilized rodent models will be discussed with emphasis on their similarities to human disease.
10450877 Frequency and spectrum of abnormalities in the bone marrow of the wrist: MR imaging findin 1999 Jun OBJECTIVE: To describe the frequency of marrow abnormalities on wrist MR imaging and the MR findings of these various abnormalities. DESIGN AND PATIENTS: Five hundred and nineteen patients were studied at 1.5 T. Two observers recorded the presence and location of avascular necrosis, occult fractures and arthritic edema [focal osteoarthritis, ulnolunate abutment, rheumatoid arthritis, septic arthritis, gouty arthritis and scapholunate advanced collapse (SLAC)]. RESULTS AND CONCLUSION: One hundred and eighty-seven (36%) patients demonstrated marrow abnormalities in the wrist, of which 101 were diagnosed as arthritis [64 (34%) as focal osteoarthritis, 17 (9%) as ulnolunate abutment, 15 (8%) as rheumatoid arthritis, 2 as septic arthritis, 2 as SLAC, and 1 as gouty arthritis]. Seventy-two patients had occult fractures and in 27 patients avascular necrosis was seen. MR imaging can reveal various abnormalities in bone marrow of the wrist when findings on radiography are normal or equivocal.
10990179 T-cell and T-cell receptor abnormalities in the immunopathogenesis of juvenile rheumatoid 2000 Sep Several lines of indirect evidence suggest that the pathologic autoimmune responses in juvenile rheumatoid arthritis may be antigen-driven and T cell-mediated. These include (1) activation markers expressed on synovial T cells suggestive of previous activation in vivo; (2) persistent oligoclonally expanded T-cell populations accumulating preferentially in the synovial compartment; (3) some T-cell receptor complementarity-determining region 3 sequence similarities between different clones in an individual patient; and (4) T-cell derived cytokines of predominantly Th1 type. Whether T-cell contribution is limited to only early stages of the disease (as appears to be the case in collagen-induced arthritis) or T cells are required for the perpetuation of the inflammation at later stages as well, still remains to be determined.
10570313 H-Ras signals to cytoskeletal machinery in induction of integrin-mediated adhesion of T ce 1999 Dec 1 The adhesive function of integrins is regulated through cytoplasmic signaling. The present study was performed to investigate the relevance of cytoplasmic signaling and cytoskeletal assembly to integrin-mediated adhesion induced by chemokines. Adhesion of T cells induced by chemokines macrophage inflammatory protein (MIP)-1alpha and MIP-1beta was inhibited by pertussis toxin, wortmannin, and cytochalasin B, suggesting that both G protein-sensitive phosphatidylinositol (PI) 3-kinase activation and cytoskeletal assemblies are involved. The chemokine-induced T cell adhesion could be mimicked by expression of small G proteins, fully activated H-RasV12, or H-RasV12Y40C mutant, which selectively binds to PI 3-kinase, in T cells, inducing activated form of LFA-1alpha and LFA-1-dependent adhesion to ICAM-1. H-Ras expression also induced F-actin polymerization which colocalized with profilin in T cells. Adult T cell leukemia (ATL) cells spontaneously adhered to ICAM-1, which depended on endogenous MIP-1alpha and MIP-1beta through activation of G protein-sensitive PI 3-kinase. H-Ras signal pathway, leading to PI 3-kinase activation, also induced active configuration of LFA-1 and LFA-1-mediated adhesion of ATL cells, whereas expression of a dominant-negative H-Ras mutant failed to do. Profilin-dependent spontaneous polymerization of F-actin in ATL cells was reduced by PI 3-kinase inhibitors. In this paper we propose that H-Ras-mediated activation of PI 3-kinase can be involved in induction of LFA-1-dependent adhesion of T cells, which is relevant to chemokine-mediated signaling, and that profilin may form an important link between chemokine- and/or H-Ras-mediated signals and F-actin polymerization, which results in triggering of LFA-1 on T cells or leukemic T cells.
9791557 Tissue-specific galactosyltransferase abnormalities in an experimental model of rheumatoid 1998 Sep OBJECTIVE: To investigate whether the observed pathophysiological similarities that develop in both the collagen induced experimental model of arthritis (CIA) and rheumatoid arthritis (RA) are associated with similar glycosylation changes, and to evaluate possible differences in the relative activity of the glycosylation enzyme beta, 1-4 galactosyltransferase (GTase) within various tissues, and thus provide a new insight into the potential pathogenic mechanisms controlling glycosylation changes. METHODS: Lymphocytic membrane-bound GTase activity was examined in 30 mice with CIA, 30 age matched controls and 10 adjuvant treated non-arthritic DBA/1 mice. Tissue-specific changes were assessed by comparison of GTase activity in peripheral (P.GTase) and paired splenic lymphocytes. In addition, we also investigated the effect that these changes may exert on the overall extracellular level of this enzyme, by assaying serum GTase (S.GTase) activity in these and a further group of 27 arthritic and 20 control mice. To analyse this synthetic abnormality in greater depth and to investigate the relevance of these glycosylation changes to the pathogenesis of arthritis, we also examined the humoral regulatory component associated with this system by assaying for both anti-collagen as well as anti-GTase antibodies. RESULTS: The induction of arthritis in DBA/1 mice results in a marked reduction in P.GTase activity, compared with age-matched unimmunised mice and the adjuvant controls. In contrast to the P.GTase, splenic GTase activity was found to be similar in all the groups examined. Correspondingly, serum GTase activity was also found to be significantly lower in the collagen induced arthritic mice. This overall reduction in beta, 1-4 GTase activity reflects the clinical severity of arthritis and is associated with increased levels of naturally occurring anti-GTase antibodies. CONCLUSIONS: The GTase defect seen in the peripheral B and T cells in rheumatoid arthritis is also evident in the arthritic DBA/1 mouse model of RA. This may indicate a common pathological process in both rheumatoid disease and CIA, in which changes in glycosylation are dependent on the aberrant modulation of GTase in circulating, but not splenic lymphocytes. The relative expression and activity of glycosyltransferases within various tissues may not only contribute to immunoglobulin G (IgG) glycosylation changes, but perhaps also the aberrant expression of cell surface carbohydrates and thus cell trafficking.
10922075 Cloning and expression of a novel human antibody-antigen pair associated with Felty's synd 2000 Aug 1 An increasing number of studies suggest the importance of antibodies in the pathogenesis of most systemic and organ-specific autoimmune diseases, although there is considerable controversy over the precise role of the autoantibodies involved. In humans, a major obstacle to progress is the identification and cloning of the relevant autoantibodies and autoantigens. Here, an approach based on the sequential use of antibody phage display and antigen expression libraries is developed and applied to a donor suffering from rheumatoid arthritis (RA), splenomegaly, and peripheral destruction of neutrophils leading to neutropenia (Felty's syndrome). An antibody phage display library was constructed from bone marrow from the donor and a high-affinity human mAb, ANA15, selected by panning against fresh neutrophils and independently by panning against a fixed cell line. The antibody showed strong staining of neutrophils and a number of cell lines. Probing of a lambdagt11 expression library from an induced myelomonocytic cell line with the mAb ANA15 identified the eukaryotic elongation factor 1A-1 (eEF1A-1) as a novel autoantigen. The specificity of ANA15 was confirmed by reactivity with both purified and recombinant eEF1A-1. Screening of a large panel of sera revealed that 66% of patients with Felty's syndrome had elevated levels of anti-eEF1A-1 antibodies. The cloning of this antibody-antigen pair should permit rational evaluation of any pathogenicity resulting from the interaction and its significance in neutropenia.
9446090 [Septic coxitis in childhood. Differential ultrasound diagnoses]. 1997 Oct The efficiency of ultrasound was tested in septic arthritis. A total of 259 children with hip pain, septic arthritis (n = 14), transient synovitis (n = 120), juvenile rheumatoid arthritis (n = 12), Legg-Calvé-Perthes disease (n = 92) and slipped capital femoral epiphysis (n = 21) were examined by ultrasound. By using the standard planes described by the DEGUM, it is possible to analyze the joint capsule, the surface of the femoral head and the periarticular structures. In cases with synovitis or joint effusion, capsular distention can be diagnosed by ultrasound. This distention is typical in septic arthritis, transient synovitis, juvenile rheumatoid arthritis, and in the onset phase of Perthes disease. Because capsular distention and osseous abnormalities in the various diseases are similar differentiation is not possible. Therefore, ultrasound cannot distinguish between septic and non-specific arthritis; capsular distention is a non-specific ultrasound sign. Immediate diagnostic puncture is necessary if septic arthritis is suspected (possible by ultrasound control). In cases with both capsular distention and osseous abnormalities, ultrasound usually allows differentiation between slipped capital femoral epiphysis/Perthes disease and septic/non-specific arthritis.