Browse

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

ID PMID Title PublicationDate abstract
9228122 Variation among rheumatologists in clinical outcomes and frequency of office visits for rh 1997 Jul OBJECTIVE: To estimate the variation among rheumatologists in clinical outcomes and frequency of office visits for patients with rheumatoid arthritis (RA), after accounting for patient demographic and clinical characteristics and treatments prescribed. METHODS: Multiple regression analysis using random effects for rheumatologists and adjustments for patient characteristics and treatments received, based on data derived from a panel study of persons with RA. RESULTS: During the years 1984-1993, rheumatologists accounted for a moderate amount of the total variation in clinical outcomes and nearly one-third of the total variation in frequency of office visits. For example, in 1993 rheumatologist associated variation in 4 clinical outcomes ranged from 16 to 25%, while the variation in office visit frequency attributable to rheumatologists stood at 46% of the total variation. However, rheumatologist associated variation in clinical outcomes was not statistically significant in any year, while variation in office visits was highly significant in all years (p < or = 0.0001). Although there was an increase in the percentage of variation attributable to rheumatologists for all outcomes examined across the years of this study, the time trend reached statistical significance only for frequency of office visits (2.4% per year; p = 0.0135) and functional status (1.6% per year; p = 0.0034). CONCLUSION: The magnitude and strength of rheumatologist associated variation in frequency of office visits, without comparable strength in the variation in clinical outcomes, may suggest inefficiencies in the use of resources for the care of persons with RA. Further work is needed to directly examine the relationship between health outcomes and resource utilization.
10527384 Immune response to a recombinant human TNFR55-IgG1 fusion protein: auto-antibodies in rheu 1999 Sep A substantial number of patients enrolled in clinical studies of TNFR55-IgG1 in TNF-neutralizing treatment of rheumatoid arthritis and multiple sclerosis developed antibodies to the recombinant human protein. To enable more detailed investigation subgroups of patients donated small blood samples. TNFR55-IgG1 reactive antibodies were affinity purified from plasma; IgM and IgG class antibodies reactive with TNFR55-IgG1 were found which varied considerably in titer and kinetics of appearance among individual patients. The affinity purified antibody fractions included specificities to the receptor moiety of TNFR55-IgG1, but also rheumatoid factor and other pre-existing antibodies directed to the IgG1 moiety. The antibodies bound to Fc receptors, but not detectably to TNFR55 at the human cell surface. No agonistic nor neutralizing activities of these antibodies were detected. Major linear epitopes clustered in the TNFR55 sequence in close proximity to the IgG1 fusion site. The relative content of antibodies to linear and conformational epitopes was highly variable among patients. Route and frequency of administration rather than underlying disease appeared to influence the major linear B cell epitopes selected.
9376977 Sesame oil in injectable gold: two drugs in one? 1997 Sep To investigate the potential anti-inflammatory effects of sesame oil, which is present in the injectable gold preparation Auromyose, the synthesis of tumour necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) by in vitro stimulated blood cells was measured before, during and after 12 weeks of dietary supplementation with 18 g of sesame oil daily in 11 healthy male volunteers. Neither TNF-alpha, PGE2 nor LTB4 production levels showed statistically significant changes during the 12 weeks of dietary supplementation with sesame oil. These results do not suggest an anti-inflammatory effect of sesame oil as present in injectable gold preparations which are used in the treatment of rheumatoid arthritis.
11600203 Detection of Fcgamma binding protein antigen in human sera and its relation with autoimmun 2001 Dec 3 Intestinal goblet cells of patients with ulcerative colitis and Crohn's disease highly express a binding protein of the Fc portion of IgG (FcgammaBP), which is entirely different from the Fcgamma receptors I,II, and III on neutrophils and macrophages. In this study, we proved the qualitative existence of FcgammaBP antigen in the sera of patients with rheumatoid arthritis and systemic lupus erythematosus, and, further, established a highly sensitive and quantitatively reproducible assay for FcgammaBP antigen in order to prevent the cross-reactivity of FcgammaBP with von Willebrand factor which has about 30% homology. This assay revealed a higher level of FcgammaBP antigen in the blood stream of patients with autoimmune diseases, especially progressive systemic sclerosis. This would suggest that abnormal production of autoantibodies reflects increased generation of FcgammaBP in goblet cells and its secretion into the circulation by an unknown mechanism.
10857783 Macrophage-derived cytokine and nuclear factor kappaB p65 expression in synovial membrane 2000 Jun OBJECTIVE: Monocyte-derived cytokines are important mediators in synovitis and represent novel therapeutic targets. This study was undertaken to analyze their expression in synovial membrane (SM) of patients with psoriatic arthritis (PsA) compared with that in skin of patients with PsA and SM of patients with rheumatoid arthritis (RA). METHODS: Multiple synovial biopsy samples (24 from patients with PsA, 20 from patients with RA, 5 from patients with osteoarthritis [OA]) and skin biopsy samples (lesional and perilesional skin from 25 PsA patients) were obtained. Standard leukocyte antigens, cytokines (tumor necrosis factor alpha [TNFalpha], interleukin-1apha [IL-1alpha], IL-1beta, IL-15, and IL-10) and the transcription factor nuclear factor KB (NF-kappaB; active p65 subunit) were localized and quantified immunohistochemically by light microscopy and digital image analysis. RESULTS: Sublining cellular infiltration, lymphoid aggregation, and vascularity were similar in PsA and RA SM. Lining layer thickness was greater in RA SM, associated with more CD68+ macrophages. In PsA SM, TNFalpha, IL-1alpha, IL-1beta, IL-15, and IL-10 were primarily localized to lining layer and perivascular macrophages, as were cells expressing the active subunit of NF-kappaB (p65). TNFalpha, IL-1p, and IL-15 expression in PsA lining layer was less than that in RA lining layer, likely reflecting lower macrophage numbers. In sublining areas, levels of TNFalpha and IL-15 were lower in PsA patients than in RA patients, whereas IL-lalpha and IL-1beta expression was equivalent. IL-10 was identified at similar levels in RA and PsA SM lining layer and sublining. Expression of NF-kappaB (p65) was equal in lining layer from both patient groups, but lower in PsA than RA sublining. Histologic findings did not correlate with clinical parameters of disease. Cytokine expression in skin did not correlate directly with that in SM. Cytokine expression was greater in PsA and RA SM than in OA SM. CONCLUSION: This study shows, for the first time, that monocyte-derived cytokines are found in PsA SM and demonstrates the relative paucity of the antiinflammatory cytokine IL-10 in PsA skin and SM. Significant divergence from RA SM expression was observed, despite similar clinical and demographic features in the 2 patient groups.
11324683 HLA transgenic mice as models of human autoimmune diseases. 2000 MHC class II alleles have been linked to several human autoimmune diseases such as rheumatoid arthritis (RA), Type I diabetes, and multiple sclerosis (MS). Although the mechanisms by which expression of certain MHC class II molecules predispose an individual to a particular autoimmune disease are not known, it is clear that increased susceptibility is associated with the polymorphic regions unique to these predisposing HLA alleles. These polymorphic differences may influence susceptibility by selecting potential autoreactive T cells during thymic education. Alternatively, nonsusceptible alleles may either delete or fail to select these potential autoimmune T cells, thus reducing the possibility of developing disease. In the periphery, the unique specificity of the HLA molecule derived from a susceptible allele may then recognize and present an autoantigenic peptide or foreign peptide that may cross-react with an autoantigen, activating these autoreactive T cells and leading to disease. To dissect these possibilities and to determine the exact role of particular HLA-DR or DQ molecules in disease susceptibility, we have generated several lines of HLA-DR and DQ transgenic mice. In this review, we present data summarizing the functions of these HLA class II molecules using well-established mouse models for autoimmune diseases.
10036694 Rheumatoid factor and antikeratin antibody are independent from presence of DR4 or DR1 in 1999 Jan BACKGROUND: Presence of HLA-DR4, rheumatoid factor, and antikeratin antibody may predict severe rheumatoid arthritis. OBJECTIVE: To investigate potential associations between HLA DR4, rheumatoid factor and antikeratin antibody in rheumatoid arthritis patients. PATIENTS AND METHODS: Retrospective review of 169 patients followed at the Rangueil Teaching Hospital rheumatology department for rheumatoid arthritis. RESULTS: No differences in prevalences of DR4 and DR1 were found between patients with and without rheumatoid factor or between patients with and without antikeratin antibody, suggesting that the production of rheumatoid factor and/or antikeratin antibody is not dependent on genetic factors. Substantial overlap was seen between rheumatoid factor and antikeratin antibody. All three parameters can be identified at first evaluation of a patient with joint disease. CONCLUSION: It would be of interest to evaluate the cumulative predictive value of DR4 or DR1, rheumatoid factor and antikeratin antibody at disease onset.
11257148 Evidence for a protective role of the human leukocyte antigen class II region in early rhe 2001 Feb OBJECTIVE: To analyse the distribution of predisposing DQ3 (DQB1*03(*04)/DQA1*03) and DQ5 (DQB1*0501/DQA1*01), shared epitope encoding and protective DRB1 alleles in patients with early rheumatoid arthritis (RA) and undifferentiated arthritis (UA). METHODS: Consecutive patients enrolled in an early arthritis clinic were DNA-typed for HLA-DQ and DR. RA patients (n=195), UA patients (n=160) and controls from the same region (n=306) were sorted according to their DQ-DR phenotypes: DQ3 vs DQ5 and the presence or absence of a protective DERAA-positive DRB1 molecule. The three groups were also sorted according to the shared epitope (SE) hypothesis. RESULTS: We observed the association of both DQ3 and DQ5 with RA. DQ3/3 homozygous individuals had the highest risk of developing disease [odds ratio (OR)=20.00]. Conversely DQ5, but not DQ3, was associated with undifferentiated arthritis (OR=2.15 vs 1.25). Consistent with these differences, DQ3-positive individuals had significantly more active disease at the first visit at the outpatient clinic than DQ5-positive patients. DRB1 alleles encoding a DERAA motif in their third hypervariable region provided a strong dominant protection against RA among DQ5-positive individuals and decreased arthritis activity among DQ3-positive patients. Individuals with SE-positive DR1, DR4 and DR10 alleles were also predisposed to RA, DR4/4 homozygous individuals having the highest risk of developing RA (OR=11.00). CONCLUSION: The DQ3-DR4/9 haplotypes are associated with RA. The DQ5-DR1/10 haplotypes are associated with less active disease, i.e. UA, and DERAA encoding DRB1 alleles modulate either predisposition to or the severity of RA. We propose that HLA polymorphism influences not only the initiation or perpetuation of RA but also protection against the disease.
9169265 A case of chrysiasis. 1997 May Chrysiasis and chrysoderma are terms used to describe permanent pigmentation of the skin due to the parenteral administration of gold salts. A case of chrysiasis, including a photomicrograph of the characteristic orange-red birefringence of gold in tissue when viewed under cross-polarized light, is presented. A review of the literature on the pathogenesis of the pigmentation seen in this disorder is also presented.
11710723 Chlamydia and Borrelia DNA in synovial fluid of patients with early undifferentiated oligo 2001 Nov OBJECTIVE: More than 50% of patients with synovitis involving 1-4 joints remain classified as having undifferentiated oligoarthritis (UOA) after 1 year of disease. The clinical presentation is often similar to that of reactive arthritis (ReA) and other spondylarthropathies or to Lyme arthritis. We therefore determined how often Chlamydia trachomatis (Ct) and Borrelia burgdorferi (Bb) can be identified in patients with UOA, by using an extensive laboratory approach. METHODS: We prospectively studied 52 patients with UOA who presented at an early synovitis clinic in a region highly endemic for Lyme disease. Patients were examined by standardized clinical and immunoserologic procedures. Synovial fluid was screened for the presence of Ct and Bb DNA by polymerase chain reaction (PCR). Urine was tested for Ct DNA by ligase chain reaction, and serum was tested for Ct antibodies by enzyme-linked immunosorbent assay and Bb antibodies by hemagglutination test and Western blotting. PCR results in the UOA patients were compared with the results in cohorts of patients with definite rheumatoid arthritis (RA), Lyme arthritis, and Chlamydia-induced arthritis (CIA). RESULTS: In the synovial fluid of 9 of 52 patients with UOA (17%), we found Ct DNA, and in 6 of the 52 patients (12%), Bb DNA was found. The frequency of bacteria-specific DNA was 50% (7 of 14) in CIA patients and 69% (11 of 16) in patients with Lyme arthritis. No Bb or Ct DNA was found in the synovial fluid of the 31 RA patients. CONCLUSION: With optimized PCR protocols, it is possible to detect considerable levels of Bb and Ct DNA in the synovial fluid of patients with UOA. Although the presence of bacterial DNA does not unequivocally prove its etiologic significance, we suggest that at least one-third of patients with UOA may have a form of ReA that involves asymptomatic primary infection.
10589360 Methotrexate and leflunomide combination therapy for patients with active rheumatoid arthr 1999 Nov An open-label, one-year study was conducted to evaluate the safety and clinical response to leflunomide and methotrexate combination therapy for rheumatoid arthritis. Study results revealed tolerable safety, no significant pharmacokinetic interactions between methotrexate and leflunomide, and suggested improved clinical response with combination therapy.
9683552 Intranasal administration of denatured type II collagen and its fragments can delay the on 1998 Jul Collagen-induced arthritis (CIA) is an autoimmune animal model for some types of human rheumatoid arthritis (RA). We have evaluated the effectiveness of intranasal administration of antigen in inhibiting CIA in DBA/1 mice. The intranasal administration of heat-denatured or trypsin-digested bovine type II collagen (CII) before immunization with CII strongly delayed the onset of CIA, whereas administration of native CII did not do so. The mice administered denatured or digested CII possessed much lower titers of anti-CII IgG2a than the control mice, whereas titers of anti-CII IgG1 and IgG2b were unchanged or slightly decreased. Responding to CII and peptides containing immunodominant T cell determinants, lymph node cells from mice administered denatured CII produced less IFN-gamma. These results suggest that intranasal administration of antigen downregulated preferentially Th1-type responses, whereas an enhanced Th2-type response was not observed. We demonstrate that the methods shown here are a possible treatment for rheumatoid arthritis.
9574564 TNF-alpha convertase enzyme from human arthritis-affected cartilage: isolation of cDNA by 1998 May 1 A snake venom-like protease isolated by a differential display screen between normal and osteoarthritis (OA)-affected cartilage (designated as cSVP) has a cDNA sequence identical to TNF-alpha convertase enzyme (TACE). TACE shows the presence of an unknown prodomain, a cysteine switch, a catalytic domain, a zinc binding region, a disintegrin region, an EGF-like domain, a transmembrane domain, and a unique cytoplasmic region. A TACE construct harboring the signal + prodomain + catalytic region (TACE-SPCdeltaDETCy), expressed in baculovirus could cleave preferentially (approximately 12-fold) the TNF-specific peptide over the matrix metalloproteases peptide in vitro. This recombinant protein also cleaved the natural substrate GST-ProTNF-alpha to TNF-alpha (17 kDa) in vitro. The mRNA for TACE, which is broadly distributed and differentially expressed in a variety of human tissues, is up-regulated in arthritis-affected cartilage, but not normal cartilage. OA-affected cartilage also expressed TNF-alpha mRNA that was not detected in normal cartilage. The OA-affected cartilage (in explant assays) spontaneously released TNF-alpha and IL-8 in ex vivo conditions. Addition of TNF-alphaR fused to IgG Fc fragment (TNF-alphaR:Fc) in the presence or absence of soluble IL-1R (with which it acted additively) significantly attenuated the spontaneous/autocrine release of articular IL-8 in this assay. These experiments demonstrate a functional paracrine/autocrine role of TNF-alpha in OA-affected cartilage that may depend, in part, on up-regulated levels of chondrocyte-derived TACE.
9759522 Expression of cell adhesion molecules and cytokines in murine antigen-induced arthritis. 1998 Jun Adhesion molecules and cytokines are important in chronic inflammatory conditions such as rheumatoid arthritis (RA) by virtue of their role in cell activation and emigration. Using immunohistochemical techniques we studied the expression of adhesion molecules and cytokines in cryopreserved sections of murine knee joint in the course of antigen-induced arthritis, an animal model of human RA. Various adhesion molecules and cytokines are expressed in the arthritic joint tissue. LFA-1, Mac-1, CD44, ICAM-1 and P-selectin were strongly expressed in the acute phase and to a lesser degree in the chronic phase of arthritis. VLA-4 and VCAM-1 appeared to be moderately expressed on day 1, L-selectin between days 1 and 3. LFA-1, Mac-1, CD44, alpha 4-integrin, ICAM-1 and the selectins were found expressed on cells of the synovial infiltrate, LFA-1, Mac-1 and ICAM-1 on the synovial lining layer, and VCAM-1 and P-selectin on endothelial cells. Expression of E-selectin could be demonstrated throughout the experiment at a low level in cells of the acute cell infiltrate. Cytokines, especially IL-2, IL-4, IL-6, TNF, and IFN-gamma, were heavily expressed during the acute phase of arthritis in cellular infiltrate. Taken together these data demonstrate that cytokines and their activation of adhesion molecules contribute to cell infiltration and activation during the initial phase of arthritis and to the induction and progression of tissue destruction in arthritic joints. These molecules might be potential targets for novel therapeutic strategies in inflammatory and arthritic disorders.
11145034 The value of sonography in the detection of bone erosions in patients with rheumatoid arth 2000 Dec OBJECTIVE: The ability to make an early, accurate diagnosis of rheumatoid arthritis (RA) has become increasingly important with the availability of new, expensive, and targeted therapies. However, plain radiography, the traditional method of detecting the characteristic bone erosions and an important adjunct in establishing a diagnosis of RA, is known to be insensitive. This study compared sonography, a modern imaging technique, with conventional radiography for the detection of erosions in the metacarpophalangeal (MCP) joints of patients with RA. METHODS: One hundred RA patients (including 40 with early disease) underwent posteroanterior radiography and sonography of the MCP joints of the dominant hand. Twenty asymptomatic control subjects also underwent sonography. Erosion sites were recorded and subsequently compared using each modality. Magnetic resonance imaging (MRI) was performed on the second MCP joint in 25 patients with early RA to confirm the pathologic specificity of sonographic erosions. Intraobserver reliability of sonography readings was assessed using video recordings of 55 MCP joint scans of RA patients, and interobserver reliability was assessed by comparing 160 MCP joint scans performed sequentially by 2 independent observers. RESULTS: Sonography detected 127 definite erosions in 56 of 100 RA patients, compared with radiographic detection of 32 erosions (26 [81%] of which coincided with sonographic erosions) in 17 of 100 patients (P < 0.0001). In early disease, sonography detected 6.5-fold more erosions than did radiography, in 7.5-fold the number of patients. In late disease, these differences were 3.4-fold and 2.7-fold, respectively. On MRI, all sonographic erosions not visible on radiography (n = 12) corresponded by site to MRI abnormalities. The Cohen-kappa values for intra- and interobserver reliability of sonography were 0.75 and 0.76, respectively. CONCLUSION: Sonography is a reliable technique that detects more erosions than radiography, especially in early RA. Sonographic erosions not seen on radiography corresponded to MRI bone abnormalities. This technology has potential in the management of patients with early RA/inflammatory arthritis and is likely to have major implications for the future practice of rheumatology.
10938595 A case report of insufficiency fracture of the Fossa acetabuli in a patient with rheumatoi 2000 Aug Aside from vertebral compression fractures, the most common site of insufficiency fractures is the pelvis and lower extremities. In the pelvis, the fractures usually occur in the ilium, the pubis and the ischium, but rarely in the fossa acetabuli. We report a severe insufficiency fracture of the fossa acetabuli in a 78-year-old woman with rheumatoid arthritis (RA). She had associated insufficiency fractures of the rib, the thoracic spine and the sacrum. In our case, senile osteoporosis was present before the onset of the fracture was recognized on radiographs, and RA and corticosteroid therapy might have further aggravated the porosis, resulting in the destruction of the fossa acetabuli. Regarding treatment for the fracture, a cemented total hip replacement without bone graft was attempted for several reasons such as the patient's activities, postoperative rehabilitation and the bone mass of the acetabulum. The postoperative course was satisfactory during study period. However, further follow-up is needed to monitor carefully how the patient will be in the future.
10036634 HLA-DRB1 motifs and heat shock proteins in rheumatoid arthritis. 1998 Susceptibility to develop Rheumatoid arthritis (RA) maps to a highly conserved amino acid motif expressed in the third hypervariable region of different HLA-DRB1 alleles. This motif, namely QKRAA, QRRAA or RRRAA helps the development of RA by an unknown mechanism. In the past ten years, we have extensively studied the unique properties of the QKRAA motif of HLA-DRB1*0401 and have found: (1) That it can constitute B and T cell epitopes on many infectious agents; (2) That it can shape the T cell repertoire; (3) That it is overrepresented in protein databases; (4) That it constitutes a binding motif for the highly conserved family of 70 kD heat shock proteins. This may cause abnormal trafficking of HLA-DRB1*0401 in B cells and/or abnormal T cell responses to bacterial and human 70 kD heat shock proteins in people who express HLA-DRB1*0401.
9313386 The importance of enhancing self-efficacy in rheumatoid arthritis. 1997 Feb OBJECTIVE: To examine relationships among changes in self-efficacy and changes in other clinically relevant outcome measures. METHOD: Subjects (n = 44) were participants in a prospective, randomized stress-management study followed over 15 months. Outcome measures included self-efficacy, depression, pain, health status, and disease activity. RESULTS: Correlational analyses revealed significant associations between changes in self-efficacy (particularly total self-efficacy) and changes in selected measures of depression, pain, health status, and disease activity. The observed associations were not due to changes in medication regimen or to nonadherence to the stress-management program. CONCLUSIONS: Evidence is provided that induced changes in self-efficacy following a stress-management program were significantly related to other clinically important outcome measures.
11395926 Liposomes as possible carriers for lactoferrin in the local treatment of inflammatory dise 2001 Jun Liposomes prepared from naturally occurring biodegradable and nontoxic lipids are good candidates for local delivery of therapeutic agents. Treatment of arthritis by intra-articular administration of anti-inflammatory drugs encapsulated in liposomes prolongs the residence time of the drug in the joint. We have previously shown that intra-articular injection of human lactoferrin (hLf), a glycoprotein that possesses anti-inflammatory and antimicrobial activities, into mice with collagen-induced arthritis reduces inflammation. We have now investigated the possibility of using liposome-entrapped hLf as a delivery system to prolong hLf retention at sites of local inflammation such as the rheumatoid joint. Entrapment of hLf in negatively charged liposomes enhanced its accumulation in cultured human synovial fibroblasts from rheumatoid arthritis (RA) patients, compared with positively charged formulations or free protein. However, in the presence of synovial fluid, positively charged liposomes with entrapped hLf were more stable than the negatively charged formulations. In vivo experiments in mice with collagen-induced arthritis showed that the positive liposomes were more efficient in prolonging the residence time of hLf in the inflamed joint as compared with other liposomes. Thus, the amount of hLf retained in the joint after 2 hr was 60% of the injected dose in the case of positive liposomes and only 16% for negative pH-sensitive liposomes. The results suggest that entrapment of hLf in positively charged liposomes may modify its pharmacodynamic profile and be of therapeutic benefit in the treatment of RA and other local inflammatory conditions.
9117185 Corticosteroid use and abuse by medical practitioners for arthritis and related disorders 1997 Jan A total of 256 consecutive patients attending our out-patient clinic in Islamabad, Pakistan, with complaints of pain in or around the joints were evaluated for use of corticosteroids prescribed by medical practitioners they had seen earlier. The appropriateness of such prescriptions and their consequent effects were assessed. Of the 256 patients, 110 (i.e. 42.5%) were identified as steroid users; some of them were suffering from conditions known to be unresponsive to this form of therapy. One hundred and one of the 256 patients had rheumatoid arthritis and 67% of these had been using steroids, mostly in an irrational manner. The general practitioners and consultants (all non-rheumatologists) were responsible for the majority of steroid prescriptions. Steroid side-effects were observed in 42/110 (38.2%) cases. This prevalent practice in Pakistan is a reflection of the state of affairs in developing countries, and indicates a need for improvement and better regulation of health care in such countries.