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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
12509611 Is thiopurine methyltransferase genetic polymorphism a major factor for withdrawal of azat 2003 Jan OBJECTIVE: To determine whether the presence of thiopurine methyltransferase (TPMT) alleles associated with reduced or absent activity of thiopurine methyltransferase is a major factor for withdrawal of azathioprine (AZA) in rheumatoid arthritis (RA) patients. METHODS: The TPMT genotype, including the variable number of tandem repeats (VNTR) pattern in the 5' untranslated region, was analysed in 111 patients with long-standing RA. Azathioprine (AZA) therapy was used in 40 patients (36%) as a disease-modifying anti-rheumatic drug. RESULTS: Seven out of 111 RA patients (6.3%) were carriers of a mutant allele, TPMT3A (G(460)-->A, A(719)-->G) being the mutant allele observed most frequently. In the group of 40 AZA-treated patients, therapy was discontinued in six patients because of side-effects and in 26 patients because of lack of efficacy. Three patients presented moderate side-effects and were homozygous for the wild-type TPMT allele, whereas the remaining three patients, who developed gastrointestinal effects with severe nausea and vomiting, were TPMT3A carriers. CONCLUSION: In this observational study, the absence of response, probably due to the low-dose scheme used, was the major cause of AZA withdrawal in our series of RA patients. TPMT genotyping may allow the use of high doses of AZA in patients with normal TPMT alleles to improve the efficacy of this immunosuppressive drug. Our data support the relationship between gastrointestinal intolerance and thiopurine metabolic imbalance.
14749980 Association of TAP2 gene polymorphisms in Chinese patients with rheumatoid arthritis. 2004 Feb The aim of this study was to investigate the association between the polymorphism of transporters associated with antigen processing ( TAP1/TAP2) genes and rheumatoid arthritis in Chinese patients. A total of 100 RA patients and 99 healthy control subjects were enrolled. Analyses with polymerase chain reaction (PCR) based restrictions were used to identify the polymorphisms of the TAP1 and TAP2 genes, which were mapped on chromosome 6. There was a significant difference in the distribution of the TAP2 gene codon 565 polymorphism frequency between the RA patients and healthy control subjects ( p<0.001). The odds ratio for the risk of the 'A' allele in RA patients was 1.60 (95% CI: 0.82-2.92). No statistical associations in the distribution of the TAP1 gene polymorphism frequency were found between RA patients and controls. There were some physical links found between TAP1/TAP2 gene polymorphism loci. However, there was no linkage observed from TAP1/TAP2 gene polymorphisms and HLA-DRB1*04 between RA patients and healthy controls. We concluded that the TAP2 gene codon 565 'A' allele was associated with RA in Chinese patients in Taiwan. Individuals possessing the 'A' allele had a higher incidence of RA. A lack of association of TAP1 gene polymorphisms between RA patients and healthy individuals was noted. The results of this study provide genetic evidence that TAP2 gene codon 565 polymorphism may play a role in RA.
12001410 [Synovial diseases of the hip]. 2002 Mar 15 Synovial diseases of the hip are often overlooked because they are far less frequent that osteoarthritis and because this joint is deep and so difficult to examine. The more important cause is septic arthritis; it requires an hospitalization in emergency. Synovial tissue may also be at the beginning of the spondylarthropathy or, more rarely, of rheumatoid arthritis. In acute forms, diagnosis must be done before any radiological destructive changes. Aspiration of the hip and synovial biopsy are necessary for the diagnosis. In subacute or chronic forms, computed tomography and/or magnetic resonance imaging are useful tools to suspect the diagnosis and to guide a biopsy.
14994388 Immune activation and depression in women with rheumatoid arthritis. 2004 Mar OBJECTIVE: We examined markers of immune activation during periods of stress and depressive symptoms in 45 female patients with rheumatoid arthritis (RA) in comparison to 106 controls with no autoimmune disease. METHODS: Depressive symptoms were recorded, clinician ratings of disease activity were made, and blood was drawn for RA patients and controls at baseline and during a designated stressful week. RESULTS: Counts of T cell subpopulations revealed significant differences between RA and control groups in proportions of CD8 and CD4 cells, with higher CD4 and lower CD8 counts for the RA participants. Significant depression by diagnosis interactions were found, revealing greater CD4 activation among RA patients who were depressed in comparison to other groups. Only marginally significant effects of stress were found on T cell counts. Interleukin 6 (IL-6) concentrations also differentiated groups, with the highest levels of IL-6 observed for depressed RA patients under stress. CONCLUSION: These findings provide new evidence that psychosocial factors play a significant role in autoimmune processes that underlie RA.
11886969 The mechanical joint score: a new clinical index of joint damage in rheumatoid arthritis. 2002 Feb OBJECTIVES: To evaluate the mechanical joint score (MJS) in terms of its reliability between observers and over time, its ease of use and its relationship with conventional measures of rheumatoid arthritis (RA) disease activity, severity and functional outcome. METHODS: The MJS was evaluated in 103 patients with reference to the following joints: total proximal interphalangeal (PIP) joints, total metacarpophalangeal (MCP) joints, wrists, elbows, shoulders, hips, knees, ankles and total metatarsophalangeal (MTP) joints. The score was based on the appearance of the joints on a scale of 0-3, 0 representing no abnormality and 3 severe abnormality or previous surgery. The MJS was evaluated in terms of its intra- and inter-observer variability and its content, construct and criterion validities. A subset of 29 patients were re-evaluated after 5 yr to examine change in MJS over time. RESULTS: The MJS performed well in terms of inter-observer and intra-observer reliability. The MJS showed strong correlation with the Larsen X-ray score of hands and feet (Spearman correlation coefficient 0.74) and with the modified Health Assessment Questionnaire (Spearman correlation coefficient 0.56) and only weak correlation with indices of disease activity, such as the Ritchie index and erythrocyte sedimentation rate. The MJS showed highly significant positive change over time. CONCLUSION: The MJS is a reliable clinical index of joint damage and may be a useful new outcome measure in RA.
12734888 Health related quality of life in women with elderly onset rheumatoid arthritis. 2003 May OBJECTIVE: To examine the association of elderly onset rheumatoid arthritis (RA) with health related quality of life in a population based cohort of older women. METHODS: A nested case-control study of elderly onset RA within the Iowa Women's Health Study (IWHS), a prospective cohort established in 1986 of 41,000 women aged 55 to 69 years. A supplemental questionnaire was mailed to 122 RA cases and 1132 frequency matched controls from the cohort. We used unconditional logistic regression and linear regression to examine the association of elderly onset RA with self-reported measures of functional disability and quality of life. RESULTS: Elderly onset RA was associated with a 6-fold risk (OR 6.0, 95% CI 3.6-10.1) of significant functional disability (Health Assessment Questionnaire score (3) 1). Similarly, elderly onset RA was significantly associated with lower physical component scores of the Medical Outcome Study Short Form-12 (37.2 +/- 10.9 vs 43.6 +/- 11.6; p < 0.001). CONCLUSION: Among a community based cohort, elderly onset RA was strongly associated with functional disability and reduced quality of life. These associations were independent of other age associated factors including depression, recent fracture, and multiple comorbidities.
11908584 Infliximab treatment in a patient with rheumatoid arthritis on hemodialysis. 2002 Mar We describe a 60-year-old woman with active rheumatoid arthritis (RA) and endstage renal disease secondary to hypertensive nephrosclerosis undergoing hemodialysis. She had tried multiple antirheumatic medications; however, their usefulness was limited due to toxic side effects or lack of efficacy. She was then treated with chimeric antitumor necrosis factor monoclonal antibody (infliximab), which resulted in immediate improvement in clinical and laboratory measures. After about 2 years of therapy, no side effects have been observed. This report expands the spectrum of infliximab to include RA patients with renal insufficiency.
12696499 Differences in the autonomic reactivity pattern to psychological load in patients with hyp 2003 As a ground-based reference study to a space experiment, a complex psychophysiological test battery (heart rate, blood pressure, skin conductance, finger temperature, forearm electromyogram during psychological loading task solving) was developed and first applied on two cohorts of subjects with different blood pressure levels at rest (53 hypertensive patients, and 30 normal controls). The data describing autonomic reactivity could be differentiated by cluster analysis into four Autonomic Outlet Types (AOT). The method was subsequently applied to 20 patients with systemic Lupus erythematosus and 13 subjects with rheumatoid arthritis to work out a discriminant function for classifying and testing it's validity. The AOT classification of all subjects showed a significant correlation with the different types of diseases.
12175106 A multicenter cost-of-illness study on rheumatoid arthritis in Italy. 2002 Jul OBJECTIVE: Rheumatoid arthritis (RA) is a chronic and disabling disease frequently leading to physical and psychological dependence, with considerable economic consequences. The aim of our study was to perform a cost-of-illness analysis for RA according to the four different levels of functional RA severity. METHODS: Direct costs (hospitalisations, treatments, diagnostics and the non-medical costs), indirect costs (productivity losses and informal care), and intangible costs (deterioration in the quality of life of patients, their families and friends assessed by the Medical Outcome Survey Short Form and the Stanford Health Assessment Questionnaire) were measured in 200 RA patients. RESULTS: The social costs--direct plus indirect costs--increased as RA worsened. The direct costs increase very significantly (p < 0.0005) among the four functional classes (respectively Euro 1643.4 - 2910.2 - 4236.5 - 5696.8), likewise the indirect costs (respectively Euro 2704.9 - 9566.4 - 12183.1 - 17249.2). Moreover social costs, analysed independently from the functional classes, are significantly higher in patients with other concomitant diseases. As far as the intangible costs are concerned, for all the areas explored by the scales used, the high impact of RA on the quality of life of RA patients was markedly evident. Female gender and co-morbidity are associated with higher costs. CONCLUSIONS: In Italy, the indirect costs account for the highest cost for management of RA patients. Considering that costs increase with RA progression, the patients who show a rapid evolution of the functional damages should be identified early based on risk indicators.
11890437 Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis. 2002 Feb OBJECTIVE: To demonstrate the effects of a very low-fat, vegan diet on patients with rheumatoid arthritis (RA). DESIGN: Single-blind dietary intervention study. SUBJECTS AND STUDY INTERVENTIONS: This study evaluated the influence of a 4-week, very low-fat (approximately 10%), vegan diet on 24 free-living subjects with RA, average age, 56 +/- 11 years old. OUTCOME MEASUREMENTS: Prestudy and poststudy assessment of RA symptomatology was performed by a rheumatologist blind to the study design. Biochemical measures and 4-day diet data were also collected. Subjects met weekly for diet instruction, compliance monitoring, and progress assessments. RESULTS: There were significant (p < 0.001) decreases in fat (69%), protein (24%), and energy (22%), and a significant increase in carbohydrate (55%) intake. All measures of RA symptomatology decreased significantly (p < 0.05), except for duration of morning stiffness (p > 0.05). Weight also decreased significantly (p < 0.001). At 4 weeks, C-reactive protein decreased 16% (ns, p > 0.05), RA factor decreased 10% (ns, p > 0.05), while erythrocyte sedimentation rate was unchanged (p > 0.05). CONCLUSION: This study showed that patients with moderate-to-severe RA, who switch to a very low-fat, vegan diet can experience significant reductions in RA symptoms.
12858436 Expression of a wide range of fibrocartilage molecules at the entheses of the alar ligamen 2003 Jul OBJECTIVE: To provide evidence for the existence of a wide range of molecules characteristic of fibrocartilage at normal alar ligament entheses, that may have a bearing on the pathogenesis of rheumatoid arthritis. The alar ligaments provide the mechanical restraint for head rotation and their integrity can be compromised in patients with RA and occasionally in those with spondyloarthropathy. METHODS: Both alar ligaments from 6 cadavers were fixed in 90% methanol and cryosectioned longitudinally. Sections were immunolabelled with antibodies against collagens, glycosaminoglycans, and proteoglycans. The immunohistochemical data were related to estimates of insertional angle change at the entheses that were calculated from measurements of ligament length and dens diameter. RESULTS: Molecules typical of fibrocartilage (including type II collagen, link protein, and aggrecan) were found at both entheses, but labelling was more prominent at the odontoid end. This correlated with a 3-fold greater insertional angle change during 40 degrees of head rotation at the attachment of the ligament to the dens. At the odontoid enthesis, fibrocartilage differentiation was most conspicuous posteriorly. CONCLUSION: The changes in insertional angle mean that compressive forces are prominent at both entheses, but particularly at the odontoid end, where the ligament partly wraps around the dens during head rotation. Thus, mechanical conditions are created that lead to pronounced fibrocartilage development, hence the expression of type II collagen, link protein, and aggrecan. The prominence of these molecules at the entheses raises the possibility that they could be antigenic targets for an autoimmune response in rheumatic diseases.
15037445 Radiography as primary outcome in rheumatoid arthritis: acceptable sample sizes for trials 2004 Nov OBJECTIVES: To investigate whether plain radiographs can show changes in joint damage due to rheumatoid arthritis (RA) within 3 months. METHODS: 188 film pairs taken with a 3 month interval were evaluated. They were scored with (chronological) and without (paired) knowledge of the sequence of the films according to the Sharp/van der Heijde method. Changes in joint damage were analysed on a group and an individual level for different subsets of patients. Sample sizes required to detect statistically and clinically significant differences were estimated based on the percentages of patients with progression larger than the smallest detectable change (SDC). RESULTS: Changes in joint damage were seen by both the chronological and the paired scoring method. The percentage of patients with progression of joint damage larger than the corresponding SDCs (1.7 and 2.4) varied in the subsets from 18% to 64% if based on the chronological change-scores and from 9% to 36% using paired change-scores. Acceptable sample size estimates were seen in several subsets, depending on (a) how the investigated drug would reduce the individual risk of progression of joint damage (by an absolute or a relative risk reduction model); (b) how damage was scored (chronological or paired); (c) the baseline risk; and (d) whether a two sided or one sided test would be used. CONCLUSIONS: Changes in joint damage due to RA can be detected reliably already within 3 months. This finding can be used to plan short term, randomised controlled trials with radiographic progression as primary outcome.
12086168 An assessment of histopathological criteria for infection in joint arthroplasty in rheumat 2002 May Intraoperative frozen section is reported to be a reliable means of identifying occult infection for preoperative evaluation of arthroplasty. The aim of this study was to determine whether the reported histopathological criteria--the existence of more than 10 polymorphonuclear cells (PMN) per high-power field--is valuable for determination of infection during the arthroplasty of patients with rheumatoid arthritis (RA). The permanent histological sections of RA synovium were analysed to study the degree of infiltration of PMNs. Furthermore, in order to examine the penetrative distribution of PMNs within the synovial tissues, immunohistochemical staining of PMNs was performed. In addition, the clinical history, from the postoperative period to the present, was investigated in 46 patients (60 joints). The presence of early- and/or late-stage postoperative infection, the development of postoperative fever, the progression of erythrocyte sedimentation rate (ESR) (more than 30 mm per hour) and the changes in CRP (more than 10 mg per litre) were further examined and compared with the histopathological tissue analyses and findings. The results demonstrated the presence of more than five PMNs per high-power field, excluding surface fibrin and inflammatory exudate in at least five separate microscopic fields in 10 joints (16.7%) of nine patients, out of 60 joints of 46 patients, in which no postoperative infection was evident. As to the magnitude of penetrative distribution of PMNs in 10 joints, there was a trend of deepening infiltration among the patients with intensive PMN infiltration. In addition, no development of postoperative fever, CRP or continuous indications of high ESR values were evident in this group. As the existence of more than 10 PMN per high-power field was not absolutely indicative of occult infection, investigation of frozen section during arthroplasty should be carefully managed.
15268638 Rheumatoid arthritis: developing pharmacological therapies. 2004 Aug Rheumatoid arthritis (RA) is a chronic inflammatory disease that often results in significant morbidity, mortality and disability. Over the past 20 years a better understanding of the pathogenesis of RA has led to the development of new approaches to disease treatment. The recent introduction of biological agents has changed the treatment paradigm for RA. The success of early biological therapies including TNF-alpha and IL-1 antagonists has spurred interest in the development of additional novel targets in the treatment of RA. Biological therapies approved for other indications, such as rituximab, are now being evaluated for the treatment of rheumatic diseases such as RA. A co-stimulatory blocker, abatacept, is also in pivotal Phase III trials. This article reviews evolving pharmacological therapies in RA with an emphasis on the newer approaches to treatment including inhibition of cognate signalling and T- and B-cell targets.
12140750 Genetic determinants of rheumatoid arthritis: the inducible nitric oxide synthase (NOS2) g 2002 Aug An association study and a linkage analysis were carried out in parallel in order to investigate the association of the inducible nitric oxide synthase (NOS2) gene promoter polymorphism with rheumatoid arthritis (RA) predisposition and/or outcome including a -954G-C mutation, a di-allelic (TAAA)(n) marker and the highly polymorphic (CCTTT). The -954G-C point mutation occurred non-polymorphic and the di-allelic (TAAA)(n) marker was not associated with RA predisposition. The (CCTTT)(n)locus showed a trend for RA association in the case-control study, however, stratification data by Class II status did not yield significant effect and overall, the family study showed no significant association nor linkage for any of the markers under study using TDT and non-parametric linkage respectively. Finally, no influence was detected regarding any of the clinical parameters tested. After evaluating for the first time the influence of NOS2 promoter polymorphism in RA, it seems to have no major effect on disease susceptibility and/or outcome.
14969072 Combination therapy in early rheumatoid arthritis. 2003 Sep The course of rheumatoid arthritis (RA) is determined early and the goals in early RA are to prevent radiologic joint degradation and to achieve optimal clinical and biological remission. Achieving these goals means that many RA patients may be candidates for combination disease-modifying therapy. We review data from randomized clinical trials regarding the impact of these treatment strategies as the initial therapy in early RA. It appears likely that the place of combination therapy will increase in the coming decades, even in very early RA patients, where the ultimate goal is persistent remission.
15334114 Fc gamma R expression on NK cells influences disease severity in rheumatoid arthritis. 2004 Nov Rheumatoid arthritis (RA) is associated with autoantibodies, the best known of which is rheumatoid factor (RF). RF/IgG complexes interact with FcgammaR on the surface of neutrophils, NK cells and monocyte/macrophages. We have analyzed the expression pattern and allelic polymorphisms of three FcgammaR genes (FcgammaRIIA, FcgammaRIIC and FcgammaRIIIA) in a large sample of RA patients and normal donors. We have found that the level of FcgammaR (CD16 and CD32) expression on NK cells is lower in RA patients than in normal individuals. Genotypic analysis demonstrated that the CD32 isoform expressed by the majority of RA patients was not the activating FcgammaRIIc1 isoform, commonly seen in normal individuals, but rather the inhibitory FcgammaRIIb isoform. The combination of the FcgammaRIIIA-176F allele with a lack of CD32 expression in NK cells appeared to be characteristic of RA subjects with aggressive disease. Since FcgammaRII and FcgammaRIIIA are predominantly expressed by NK cells, these data further suggest that FcgammaR-mediated activation of NK cells could be a disease-determining factor in RA patients.
15370716 Death rates and causes of death in patients with rheumatoid arthritis: a population-based 2004 OBJECTIVE: To assess the mortality and causes of death in a cross-sectional population-based study of 1042 patients with rheumatoid arthritis (RA). METHODS: In 1988, 604 RA patients [470 females (F), 134 males (M)] and 457 age- and sex-matched controls (352 F, 105 M) were examined prospectively (participants) and 438 (183 F, 81 M) non-participant RA patients retrospectively. In 1999, vital status and causes of death were determined. Mortality in the total RA population was compared to that in the general population, and that among participant RA patients to their matched controls. RESULTS: A total of 384 (37%) RA patients and 71 (16%) controls died. RA patients had increased mortality compared to the general population (standardized mortality ratios SMR 2.64) or controls (1.71). This was observed in both sexes. Over 40% of deaths in all groups were due to cardiovascular diseases. RA patients were at increased risk of dying of urogenital, gastrointestinal, respiratory and cardiovascular diseases, infections, and cancers when compared to the general population or controls. CONCLUSIONS: Our results show that a cross-sectional cohort of RA patients had an increased risk of death from various causes.
14967878 Haemorheological variables as a rheumatoid arthritis activity indicator. 2004 OBJECTIVE: To investigate if blood hyperviscosity in RA patients is due to a reduced erythrocyte deformability and, therefore, turning it into a reliable activity indicator, as well as a therapy follow-up marker for this pathology. METHODS: (1) The haemorheological profile consisting of erythrocyte deformability, blood and plasma viscosity, and erythrocyte membrane fluidity was determined in 24 AR patients and 17 healthy controls. (2) A 4 year follow-up was carried on in 16 patients monitoring blood viscosity, erythrocyte deformability and biochemical variables in relation to clinical assessment of disease activity (Disease Activity Score "DAS 28-4"). RESULTS: Erythrocyte deformability and membrane fluidity were impaired in RA patients compared to controls (p<0.001). Blood viscosity was significantly increased and correlated with the cell rigidity index (r=0.85, p<0.0000) in RA patients. The follow-up showed a good correlation between haemorheological parameters and DAS 28-4 during disease evolution. CONCLUSION: our results support the hypothesis that in RA, blood hyperviscosity is determined by deformability loss, which in turn is due to a membrane rigidization. This could evidenced that a widespread cell membrane damage is expressed through an impaired erythrocyte deformability, turning haemorheological parameters into reliable tools to study disease evolution. The follow-up study enabled us to confirm that erythrocyte deformability is an efficient indicator of rheumatoid arthritis activity.
14636538 [Autoantibodies in the diagnosis of rheumatoid arthritis. Utility of anti-cyclic citrullin 2003 Nov 8 Rheumatoid arthritis (RA) is one of the commonest inflammatory joint diseases, affecting about 1% of population. Despite its high prevalence, many aspects of its etiopathogeny remain unclarified. Recently, some important findings related to RA pathogenesis with a number of consequences on the treatment and prognosis of this aggressive disease have been reported. It is important to diagnose and to treat the disease early to avoid long-term damage. However, the search for a specific and sensitive serological test to early identify RA patients has yielded poor results. Autoantibodies are found in the sera of RA patients with a variable prevalence and have been classified into RA-specific and RA-unspecific antibodies. It has been recently demonstrated that many of those RA-specific autoantibodies recognize peptides that contain citrulline residues and, thus, a new test to measure the presence of anti-cyclic citrullinated peptides (CCP) antibodies has been developed. Research publications about the utility of anti-CCP antibodies not only in the diagnosis, but also in the prognosis, of RA are increasing exponentially. In fact, the value of the measurement of anti-CCP antibodies is already widely recognized. This review summarizes the most important data about the autoantibodies employed to date in the diagnosis of RA, including anti-CCP antibodies.