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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
12117681 Serum interleukin 18 and interleukin 18 binding protein in rheumatoid arthritis. 2002 Aug OBJECTIVE: To measure serum interleukin 18 (IL18) and IL18 binding protein (IL18BP) levels in patients with inflammatory arthropathies, and to identify associations with disease status and the response to treatment. METHODS: Serum samples were obtained before and after methotrexate treatment from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) attending an early arthritis clinic. IL18 and IL18BP were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Sixty patients with RA and 13 with PsA were evaluated. Serum IL18 levels were significantly higher in RA than in PsA (p<0.001). After six months' treatment with methotrexate, IL18 levels were reduced, but the differences were not significant (p=0.052). In cross sectional analyses, no correlations between IL18 levels and measures of disease activity or structural damage in RA were found. In longitudinal analyses, no correlations between IL18 levels and the response to treatment or the degree of progressive joint damage were found. Similarly, IL18BP levels were raised in RA, and were not associated with measures of the clinical status or the response to treatment. CONCLUSION: Raised serum levels of IL18 are consistent with a pathophysiological role in RA. However, in this study measurement of circulating IL18 and IL18BP did not correlate significantly with clinical measures of disease activity or the response to treatment in patients with early RA.
11953969 Interaction between heat-shock protein 73 and HLA-DRB1 alleles associated or not with rheu 2002 Apr OBJECTIVE: HLA-DRB1 alleles whose third hypervariable region contains a QKRAA/QRRAA/RRRAA motif are associated with rheumatoid arthritis (RA) through unknown mechanisms. We previously demonstrated that the QKRAA motif was also expressed on the Escherichia coli 40-kd heat-shock protein (HSP) DnaJ. The QKRAA motif helps DnaJ bind its partner chaperone, the E coli 70-kd HSP DnaK. Furthermore, we observed that in lymphoblastoid cells, Hsp73, the constitutive 70-kd HSP, associates with HLA-DRB1*0401 (an allele with a QKRAA motif) and targets it to lysosomes. In this study, we sought to classify different HLA-DRB1 alleles according to their ability to bind Hsp73. METHODS: To evaluate how well different HLA-DRB1 alleles could bind Hsp73, we developed a quantitative precipitation assay and a direct binding assay. RESULTS: Quantitative precipitation assay from total cellular proteins and from lysosomal extracts demonstrated that RA-associated HLA-DRB1 alleles bound Hsp73 better than did HLA-DRB1 alleles that were not associated with RA. HLA-DRB1*0401 was the best Hsp73 binder. These findings were confirmed by direct binding assay between purified proteins. CONCLUSION: HLA-DRB1*0401 was the best Hsp73 binder among the 8 different HLA-DRB1 alleles that were tested.
11934961 Investigation of the chronic pulmonary effects of low-dose oral methotrexate in patients w 2002 Mar OBJECTIVE: Methotrexate has a well-recognized side-effect of acute hypersensitivity pneumonitis. There is concern about whether chronic pulmonary toxicity can occur with methotrexate treatment. Our objective was to compare chest high-resolution computed tomography (HRCT) findings and serial pulmonary function tests in rheumatoid arthritis (RA) patients on methotrexate with findings for a control group of patients with RA who were not being treated with methotrexate. METHODS: Study patients had an initial chest radiograph, full pulmonary function tests and chest HRCT. Pulmonary function tests were then performed regularly over a 2-yr period. RESULTS: Fifty-five RA patients on methotrexate and 73 control patients with RA were enrolled for the study. Mean dose of methotrexate was 10.7 mg/week (S.D. 2.5 mg/week) and mean duration of treatment at entry into the study was 30 (20) months. Twenty per cent of patients with RA treated with methotrexate had pulmonary fibrosis (PF) on initial HRCT compared with 23% in the control group. When the patients with and without PF were compared, there was no statistical difference in the duration (mean difference -4.18 months, P=0.237) or dose (mean difference -0.8 mg/week P=0.52) of methotrexate therapy. Mean changes after 2 yr in forced expiratory volume, forced vital capacity, diffusion capacity for carbon monoxide and residual volumes were not different in the methotrexate group compared with the control group. CONCLUSION: There is no evidence to suggest clinically, from HRCT assessment or serial pulmonary function tests, that low-dose methotrexate is associated with chronic interstitial lung disease.
11823356 Relative importance of genetic effects in rheumatoid arthritis: historical cohort study of 2002 Feb 2 OBJECTIVE: To determine the relative importance of environmental and genetic effects in the development of rheumatoid arthritis. DESIGN: Historical cohort study with record linkage between a twin registry and the Danish discharge registry as well as the Danish national registry of deaths used to estimate completeness. SETTING: Two population based nationwide twin birth cohorts. PARTICIPANTS: 37 338 twins were sent a questionnaire about rheumatic diseases. Self reported rheumatoid arthritis was verified by clinical examination and from medical records. MAIN OUTCOME MEASURES: The probandwise concordance rate of rheumatoid arthritis in monozygotic and dizygotic twins. RESULTS: The response rate was 84.7%. Rheumatoid arthritis was verified in 13 monozygotic and 36 dizygotic twins. There were no concordant monozygotic twin pairs and two concordant dizygotic twin pairs. Based on capture-recapture methods the probability of ascertainment was 78.3%. The probandwise concordance rate was 0 (95% confidence interval 0 to 24.7) in monozygotic twins and 8.8 (1.9 to 23.7) in dizygotic twins. CONCLUSION: Genes are of minor importance in the development of rheumatoid arthritis.
15358176 The human Duffy antigen binds selected inflammatory but not homeostatic chemokines. 2004 Aug 20 The aim of the study was to compare the ability of the human Duffy antigen to bind homeostatic and inflammatory chemokines. Homeostatic chemokines did not bind to the Duffy antigen on erythrocytes with high affinity. In contrast, 60% of inflammatory chemokines bound strongly to Duffy, with no obvious preference for CXC or CC classes. It was investigated if this binding profile was reflected in the binding pattern of endothelial cells. Two examples of homeostatic (125I-CXCL12 and 125I-CCL21) and inflammatory (125I-CXCL8 and 125I-CCL5) chemokines were incubated with human synovia. In agreement with the erythrocyte binding data, intense specific signals for CXCL8 and CCL5 binding were found on endothelial cells, whereas CXCL12 and CCL21 showed only weak binding to these cells. Our study provides evidence that the human Duffy antigen binds selected inflammatory, but not homeostatic, chemokines and that this binding pattern is reflected by endothelial cells within inflamed and non-inflamed tissue.
14626516 Optimizing outcomes in rheumatoid arthritis. 2003 Sep A chronic systemic inflammatory disease, rheumatoid arthritis can cause progressive joint destruction, deformity, disability, and premature death. Pain management is an important component of patient care, and short-term opioid analgesics should be considered in those with severe arthritis pain. Treatment with DMARDs should be initiated early in the course of the disease to control synovitis and disease progression. Biological therapies that block specific cytokines are important advances in the treatment of rheumatoid arthritis.
15077297 Increased prevalence of semaphorin 3C, a repellent of sympathetic nerve fibers, in the syn 2004 Apr OBJECTIVE: The presence of selective sympathetic nerve repellents, i.e., semaphorins, may be responsible for the observed reduction of sympathetic innervation in the synovial tissue of patients with rheumatoid arthritis (RA). This study was undertaken to investigate the presence of different semaphorins in synovial tissue of patients with RA, patients with osteoarthritis (OA), and control subjects without inflammation. METHODS: In situ hybridizations with digoxigenin-labeled RNA probes directed against different semaphorins were performed. The presence of semaphorin 3C (S3C) in the synovial tissue of 10 RA, 10 OA, and 5 control subjects was investigated using a polyclonal antiserum directed against S3C. RESULTS: All in situ hybridizations revealed the presence of S3C messenger RNA, but no other investigated semaphorin (i.e., against primary afferent sensory nerve fibers), in the synovial tissue of RA and OA patients. Immunohistologic double staining demonstrated that macrophages and fibroblasts were positive for S3C protein. Quantitative analysis of S3C protein staining showed an increased density of S3C-positive cells in the synovial tissue of RA patients (mean +/- SEM 339 +/- 65 cells/mm(2)) in comparison with OA patients (168 +/- 27/mm(2); P = 0.031 versus RA) and controls (126 +/- 26/mm(2); P = 0.027 versus RA). Studies of the relationship between sympathetic nerve fiber density and S3C-positive cell density in the tissue of all patients showed that RA patients generally had lower densities of sympathetic nerve fibers and higher densities of S3C-positive cells than OA patients and control subjects. CONCLUSION: These findings suggest that S3C from macrophages and fibroblasts, which is selectively directed against sympathetic nerve fibers, could be one element responsible for reduced sympathetic innervation in RA tissue. The inability of sympathetic nerve fibers to reinnervate synovial tissue could contribute to the chronic nature of RA.
12915155 Co-morbidity in rheumatoid arthritis. 2003 Oct Rheumatoid arthritis (RA) affects approximately 0.5-1% of the population and imposes substantial societal costs including an increased risk of work-related disability and accelerated mortality. It is increasingly clear that RA-related co-morbidities, including cardiovascular disease (CVD), infection, osteoporosis, lymphoproliferative malignancy, and peptic ulcer disease, serve as major determinants of disease-associated outcome. In this review, the impact of these select co-morbidities on RA outcome is discussed. In addition, this review explores potential mechanisms underlying their association with RA, the possible iatrogenic role of agents used to treat the disease, and measures aimed at both prevention and treatment of disease-specific co-morbidity.
11819145 Computer-assisted Magerl's transarticular screw fixation for atlantoaxial subluxation. 2002 We report two patients with rheumatoid arthritis in whom posterior atlantoaxial fixation was carried out using transarticular screws with computer assistance. Two bilateral transarticular screws were inserted in one patient; however, in the other patient, only a unilateral screw was used, because computerized images showed that the vertebral artery at the other side was placed too medially to allow insertion of the screw. Neither of these patients had any neurovascular complications after surgery. Computer-assisted surgery is useful for avoiding neurovascular complications with transarticular screw fixation of C1-2.
12841142 [Comparative analysis of the quality of life of patients with painful temporomandibular jo 2003 The quality of life was assessed in 36 patients with painful dysfunction of the temporomandibular joint (TMJ) and 73 patients with TMJ dysfunctions suffering from rheumatoid arthritis. A more significant negative time course of the parameters was observed in patients with rheumatoid arthritis and more positive shifts in patients with isolated TMJ dysfunction without rheumatoid arthritis.
12528104 Functional disability in rheumatoid arthritis patients compared with a community populatio 2003 Jan OBJECTIVE: To compare Health Assessment Questionnaire (HAQ) scores of patients with rheumatoid arthritis (RA) with HAQ scores from a sex- and age-adjusted population. METHODS: Patients with RA (n = 1,095) and control subjects (n = 1,530) completed a mailed questionnaire that comprised the HAQ, pain and global health scores, education level, and comorbidities, as well as height, weight, and lifestyle attitudes, including smoking and exercise habits. RESULTS: The HAQ scores increased (indicating declining function) with older age in patients and controls. The HAQ scores were above the reference values (>95th percentile of the HAQ scores of the age- and sex-matched population) in 17-45% of women with RA and in 7-32% of men with RA ages 30-79 years, while the HAQ scores of the patients > or =80 years were similar to those of the age- and sex-matched population. In a logistic regression model, the odds ratio for disability (HAQ score > or =1; at least some difficulties in most activities of daily living) was 7.7 (95% confidence interval 5.3-11.1; P < 0.001) among patients with RA compared with community controls, when adjusted for age, sex, education, smoking, exercise, body mass index, number of comorbidities, and pain. CONCLUSION: RA is associated with a >7-fold risk of disability compared with that in a general population of adults in the same community. The impact of disability due to RA appears to be greater in younger and middle-age people than in elderly patients.
15370715 Second generation anti-cyclic citrullinated peptide (anti-CCP2) antibodies can replace oth 2004 We compared the diagnostic performance of anti-cyclic citrullinated peptide antibodies detected with second-generation enzyme immunoassay (anti-CCP2) with that of IgM-rheumatoid factor (RF), anti-perinuclear factor (APF), and anti-keratin antibodies (AKA). The sensitivity of anti-CCP2 was better than that of APF and AKA: they were detected in 25% rheumatoid arthritis (RA) patients without detectable APF or AKA. Their specificity, evaluated in other inflammatory rheumatic disease, was similar to that of APF and AKA. Despite the lower specificity, IgM-RF in combination with anti-CCP2 is interesting, as they do not completely overlap. Anti-CCP2 antibody detection seems to be a good alternative to other anti-filaggrin antibodies in the diagnosis of RA.
12084545 A biomechanical analysis of the rheumatoid index finger after joint arthroplasty. 2002 Jun OBJECTIVE: To determine the mechanisms responsible for the recurrence of ulnar drift after metacarpophalangeal joint arthroplasty in the rheumatoid hand. DESIGN: A three-dimensional biomechanical model of the index finger joints was used to predict the implant loads during several activities of daily living. BACKGROUND: Post-operative clinical evaluation of Sutter metacarpophalangeal prostheses shows a high incidence of fracture and recurrent deformity. METHODS: A six-component force transducer in conjunction with a six-camera motion analysis system were used to obtain kinematic and external loading data from eight patients with rheumatoid arthritis during several simulated activities. These data were used as input into a three-dimensional biomechanical model of the implant and interphalangeal joints of the index finger. Tendon lines of action and moment arms were obtained using a series of MRI scans and CAD modelling techniques. RESULTS: Implant forces were oriented in a radial and dorsal direction to resist the ulnarpalmarly pull of tendons associated with the metacarpophalangeal joint. CONCLUSIONS: The recurrence of ulnar drift is attributable to fatigue failure of the prostheses. After fracture the implant is unable to support the repetitive loading patterns experienced during activities of daily living. RELEVANCE: Understanding the mechanisms responsible for the recurrence of ulnar drift and implant failure is a step towards improving the prosthesis design, surgical procedures and ultimately the patient's prognosis.
12166073 [Introduction, appreciation of plasma enzyme]. 2002 Jun The heterogeneities of tissue enzymes and the enzyme distribution patterns of organs, tissues and plasma have now been established by many findings in various cases and diseases. Based on these precise laboratory data, the fields of clinical enzymology has been developed so as to analyze the very specific pathophysiological state in specific disorders. The characteristics of tumor-producing enzymes and genetically modified enzymes were additionally clarified by advances in molecular technology. Enzyme linked immunoglobulins were newly categorized enzyme abnormalities found in plasma enzymes. Genetical abnormalities of plasma enzymes fully explained the clotting abnormalities, hyper coagulability and hyperlipidemia. Based on these advances, the roles and future of clinical enzymology will be presented shown and discussed in this symposium.
14748104 Souter-Strathclyde total elbow arthroplasty: medium-term results. 2003 Dec The Souter-Strathclyde unconstrained elbow prosthesis was prospectively studied in 36 patients (45 prostheses) with rheumatoid arthritis (Larsen grade 4 and grade 5). The mean age of the patients at the time of operation was 63 years (range: 39 to 75 years). Eight patients (9 prostheses) died within five years of implantation, from causes unrelated to the elbow arthroplasty. One patient was lost to follow-up, leaving 27 patients (35 prostheses) for review. The mean length of follow-up was 98 months (range: 60 to 174 months). At 8.2 years follow-up, the prosthesis showed a probability of survival of 76% (SD 9%) with revision of the humeral component as an end point; the percentage dropped to 67% (SD 9%) when radiographic loosening was taken as an end-point. Survival of the ulnar component was 98%. Loosening of the humeral component seems to be related to both the short humeral stem and a persistent extension deficit.
15593216 Evidence for a novel rheumatoid arthritis susceptibility locus on chromosome 6p. 2004 Dec OBJECTIVE: To investigate whether the large linkage peak on chromosome 6p harbors rheumatoid arthritis (RA) susceptibility loci in addition to the well-characterized HLA-DRB1 gene. METHODS: DNA samples obtained from 377 UK RA affected sibling pair (ASP) families, comprising test (181 ASPs) and replication (196 ASPs) cohorts, were used for linkage analysis. Three hundred eighty-four patients with RA derived from a subset of 192 ASPs were compared with a panel of 288 unrelated healthy controls for association studies. Samples were genotyped for 35 microsatellites and 25 single-nucleotide polymorphisms (SNPs). RESULTS: In the test cohort, the maximum logarithm of odds (LOD) score was obtained over D6S1260 (LOD 7.1). Evidence for linkage to the telomeric portion of the peak was increased in subsets of ASPs in which both individuals had erosive disease or both carried 2 copies of the shared epitope. HLA-A, HLA-DRB1, and 8 additional markers showed evidence of linkage in the presence of association with RA (using the extended transmission disequilibrium test [ETDT]). The positive ETDT result for 2 adjacent markers (D6S1665 and 210901-4) mapping to the telomeric end of the linked region ( approximately 11 Mb from DRB1) was replicated (for D6S1665) in the second cohort of ASPs. Haplotypic overtransmission of pairwise combinations between D6S1665*7 and 210901-4*4 was identified through the TDTPhase program. Multipoint conditional analysis showed this effect to be independent of HLA-DRB1. SNP-based association studies of the region identified a 4-marker haplotype in the DEK gene that was significantly associated with RA (P = 0.009). CONCLUSION: Evidence has been presented for an RA susceptibility locus mapping under the linkage peak on 6p, 11 Mb telomeric of HLA-DRB1. Preliminary association data implicate the gene DEK.
15077293 A functional haplotype of the PADI4 gene associated with rheumatoid arthritis in a Japanes 2004 Apr OBJECTIVE: In the era of postgenomic research, linkage- and association-based strategies are beginning to reveal novel complex disease genes. Using such an approach, a functional haplotype of the peptidylarginine deiminase 4 gene (PADI4) has recently been identified as a gene conferring susceptibility to rheumatoid arthritis (RA) in a Japanese population. In the present study, we investigated the association of single-nucleotide polymorphisms (SNPs) in the PADI4 gene with RA in a UK population. METHODS: Association with 4 exonic SNPs (padi4_89*G/A, padi4_90*T/C, padi4_92*G/C, and padi4_104*T/C), mapping to the PADI4 gene and defining a haplotype previously reported to be associated with RA, was investigated. Genotyping was performed using 5' allelic discrimination assays. Estimated haplotypes were generated using the expectation-maximization algorithm, and frequencies of the SNPs and haplotypes were compared between unrelated Caucasian RA patients from the UK (n = 839) and population controls (n = 481). RESULTS: Allele frequencies for the 4 SNPs in the UK population were similar to those reported in the Japanese control population, but none of these was associated with RA. As in the Japanese population, the SNPs in the UK population defined 2 major haplotypes, but neither was associated with RA (P = 0.79). CONCLUSION: A PADI4 susceptibility haplotype associated with RA in a Japanese population is not associated with RA in a UK population. Other genes involved in the citrullinating pathway remain strong candidate RA-susceptibility genes and require further investigation.
12772061 [The BIAX total wrist prosthesis as an alternative to arthrodesis in degenerative and post 2003 Jan The BIAX total wrist prosthesis was first implanted 1983 by Beckenbaugh in the United States. From a total of twenty-one BIAX-prostheses between March 2001 and February 2002, we have inserted eleven in patients for degenerative arthrosis, eight for posttraumatic arthrosis and two for rheumatoid arthritis of the wrist. The average age of the patients was 53.0 +/- 10.7 years with a follow-up between eleven and fourteen months on an average of one year. The motion of the operated joints was preserved on average. We have taken pain as the main criterion for the success of the operation and distinguished between pain at rest, in motion and under exertion. All patients showed a very good pain relief of 5 1/2 values from 6 1/2 before to one after surgery on a scale from one to ten. Pain relief is less under exertion, thus we are reserved with heavy workers of the implantation of the prosthesis. Apart from that, the indication corresponds to the arthrodesis of the wrist. The satisfaction of patients with the prosthesis is very high: 17 patients declared it was much better, three declared it was better and only one patient said it was unchanged. Complications occurred in six patients. The main complication was the postoperative dislocation of the prosthesis in three patients. After repositioning, the joints were long-term stable. The straight secured surgical technique is described in detail. For the majority of patients with posttraumatic or degenerative arthrosis, as well as with rheumatoid arthritis, the BIAX wrist prosthesis is recommended as a first-time operation as an alternative to wrist arthrodesis due to pain relief with preservation of joint motion and good acceptance among patients.
14563458 Recent data on the role for angiogenesis in rheumatoid arthritis. 2003 Sep Angiogenesis is central to the development and perpetuation of rheumatoid synovitis. Vascular endothelial growth factor (VEGF), the main mediator of angiogenesis, is found in the synovial fluid and serum of patients with rheumatoid arthritis (RA), and its expression is correlated with disease severity. Compelling evidence that VEGF is involved in synovitis has been obtained from experimental models of RA. In particular, VEGF inhibition by synthetic compounds (e.g. TNP-470) or by naturally occurring factors (e.g., the soluble VEGF receptor) produce therapeutic effects. Angiopoietin-1, a recently discovered growth factor specific for neovascularization, is expressed within the rheumatoid synovium and may be stimulated by TNF-alpha. Other compounds, including integrins, fibroblast growth factor, and proinflammatory cytokines contribute to joint angiogenesis and, therefore, to the development of rheumatoid synovitis. Assessing vascularity may prove useful for evaluating or even predicting bone destruction. Furthermore, inhibition of angiogenesis may prove useful as an adjunct to current anti-inflammatory treatments.
15364784 Eosinophilic pneumonia as an initial manifestation of rheumatoid arthritis. 2004 Sep Rheumatoid arthritis is a systemic disease that may have pulmonary manifestations. We describe a case of eosinophilic pneumonia as the primary presentation of rheumatoid arthritis. While several cases of acute and chronic eosinophilic pneumonia have been reported in patients with preexisting rheumatoid arthritis, this is the first case reported in which the eosinophilic lung disease was the initial manifestation of systemic rheumatoid arthritis.