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ID PMID Title PublicationDate abstract
17309132 Influence of HLA-DRB1 genes and the shared epitope on genetic susceptibility to rheumatoid 2007 Apr OBJECTIVE: To investigate the association of predisposing and protective HLA-DRB1 alleles with rheumatoid arthritis (RA) and its clinical markers in a Taiwanese population. METHODS: A total of 273 patients with RA and 480 healthy controls, all of Taiwanese origin, were genotyped for HLA-DRB1 alleles by polymerase chain reaction and sequence-based typing assays. The associations between RA and HLA-DRB1 alleles and genotypes were investigated by chi-squared test. RESULTS: The DRB1*0405 and *1001 phenotypes showed the most significant associations with RA (OR 4.04, 95% CI 2.84-5.77, pc = 3.2 10(-14); OR 5.25, 95% CI 2.10-13.06, pc = 3.0 10(-3), respectively). Individuals carrying single or double doses of the shared epitope (SE/non-SE or SE/SE) had higher risks of RA. The compound heterozygote of DRB1*0405/*1001 showed the largest increase in RA risk (OR 15.8, 95% CI 2.48-100.7, pc = 0.004). Single or double doses of SE alleles were significantly associated with a higher bone erosion rate. Rheumatoid factor positivity and bone erosion were more frequent in patients with at least one copy of DRB1*0405. CONCLUSION: Our results show that SE-encoding HLA-DRB1*0405 and *1001 are associated with RA in a Taiwanese population; this is the first time DRB1*1001 has been described in persons of Asian ethnicity. Heterozygotes of DRB1*0405 and *1001 predicted the strongest susceptibility to RA, suggesting that this genotype enhances susceptibility to RA in Taiwanese.
17896806 Bone mineral density in older adult patients with rheumatoid arthritis: an analysis of NHA 2007 Oct OBJECTIVE: Several studies suggest that bone mineral density (BMD) is reduced in rheumatoid arthritis (RA). However, it is unclear whether this relationship holds in a representative community-based typical RA population. We examined the relationship between BMD and RA in a representative US population-based sample from the Third National Health and Nutrition Examination Survey (NHANES III: 1988-1994). METHODS: We selected subjects over age 60 with RA from NHANES III using previously described methods. Femoral neck BMD (FN-BMD) measured by dual-energy x-ray absorptiometry was compared for the RA (n = 106) and non-RA cohorts (n = 4,277). Multivariable linear regression models included known risk factors for osteoporosis. Further adjusted analyses compared the BMD among subgroups of patients with RA, such as those taking methotrexate (MTX), those with positive rheumatoid factor (RF), and those with elevated C-reactive protein (CRP). RESULTS: Patients with RA more frequently reported poor health, a history of falling, cognitive impairment, early menopause, a history of chronic obstructive lung disease, higher total calcium intake, and thiazide use than the non-RA subjects (all p < 0.05). Adjusted FN-BMD was similar between the patients with RA (0.71 g/cm2) and non-RA subjects (0.72 g/cm2; p = 0.5). Among patients with RA, reduced BMD tended to be seen with MTX use (0.60 g/cm2, p = 0.07), CRP above 1 mg/dl (0.66 g/cm2, p = 0.09), and positive RF in female patients (0.68 g/cm2, p = 0.056). However, none of these findings reached statistical significance. CONCLUSIONS: Among a US population-based representative sample, FN-BMD was similar in RA and non-RA patients. Several characteristics of patients with RA may be associated with reduced BMD.
16697258 B cell depletion therapy in systemic rheumatic diseases: different strokes for different f 2006 Oct Autoantibodies have, until recently, been the overriding focus of investigators of autoantibody-associated diseases. Increasing attention is now being paid to B cells, which not only are the producers of autoantibodies but also contribute to autoimmune disease via autoantibody-independent mechanisms. Therapeutic measures that target B cells for depletion are gaining in popularity. In this review, we will focus on two distinct approaches of depleting B cells; one employing a direct-kill approach by engagement of B cell surface CD20 with an anti-CD20 monoclonal antibody (rituximab), and the other employing an indirect starvation approach by neutralization of B lymphocyte stimulator (BLyS), a potent B cell survival factor. Among the systemic immune-based rheumatic disorders, we will focus on rheumatoid arthritis and systemic lupus erythematosus, two disorders for which therapeutic B cell targeting is being intensely investigated.
16426939 Fever of unknown origin caused by late-onset rheumatoid arthritis. 2006 Jan Fever of unknown origin (FUO) is always a diagnostic challenge. The causes of FUO are legion and may be due to malignancy, infection, collagen vascular disease, and a variety of other unusual disorders. Currently, malignancies-followed by infectious etiologies-are the most common cause of FUO. We present an elderly female patient with an FUO who was thought to have subacute bacterial endocarditis because of an antecedent history of recent dental work. Subacute bacterial endocarditis was ruled out on the basis of negative cultures and negative transesophageal echocardiography. No evidence for an infectious disease or neoplastic etiology could be demonstrated in this patient. The diagnosis of FUO is most difficult when there is a paucity of clues from the history and physical examination, as was the case in this patient. Nonspecific laboratory tests included highly increased erythrocyte sedimentation rate (>or=100 mm/h), highly increased C-reactive protein, relative lymphocytopenia, and chronic thrombocytosis. These findings are compatible with a variety of infectious and inflammatory disorders. No evidence could be found for vasculitis. The only laboratory diagnostic findings present in her case were a highly increased rheumatoid factor titer and perinuclear antineutrophilic cytoplasmic antibody level. Polymyalgia rheumatica/temporal arteritis, systemic lupus erythematosus, and adult Still's disease were ruled out. The patient's FUO was best explained by the finding of late-onset rheumatoid arthritis (LORA), which is characterized by acute onset in elderly patients without the usual musculoskeletal manifestations of rheumatoid arthritis. Both the highly increased rheumatoid factor titer and perinuclear antineutrophilic cytoplasmic antibody level in the absence of an alternate explanation indicate that the FUO in this patient was caused by LORA.
17785296 Veterinary autoimmunity: autoimmune diseases in domestic animals. 2007 Aug The first spontaneous animal model of autoimmunity was the New Zealand black mouse, discovered in 1959. Interestingly, although several models of induced autoimmunity were demonstrated in a variety of rodents, the recognition of autoimmune disease in dogs came somewhat later. Dog breeding and selection of traits within certain dog breeds have become an important enterprise with intensive husbandry and selection criteria being applied to each breed standard. This has resulted in breeding for specific phenotypic characteristics. This selection has inadvertently led to the propagation of a number of autoimmune diseases in dogs. For example, systemic lupus erythematosus (SLE), autoimmune hemolytic anemia and thrombocytopenia, autoimmune myasthenia gravis, and diabetes mellitus are now fairly common. In the final analysis, the appearance of autoimmunity in dogs reflects their breeding selection and illustrates the importance of genetics in the development of autoimmune disease.
17490834 Arytenoid adduction to treat impaired adduction of the vocal fold due to rheumatoid arthri 2007 Dec Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane and causing joint damage and bone destruction. The symptoms of cricoarytenoid joint (CJ) arthritis often include hoarseness, and a sense of pharyngeal fullness in the throat. Sometimes, in cases with bilateral CJ involvement, an urgent tracheostomy might be required for acute airway obstruction. In this report, we describe a woman suffering from aphonia due to hampered adduction of the vocal fold which was caused by RA with unilateral CJ involvement. Arytenoid adduction surgery on the affected side was performed. She retrieved a normal voice immediately after the surgery.
16079171 Growth and infectious exposure during infancy and the risk of rheumatoid factor in adult l 2006 Mar BACKGROUND: The contribution of the environment to rheumatoid arthritis (RA) remains uncertain. Intrauterine and early postnatal life may be important. Rheumatoid factor (RF) found in around 10% of the normal population confers a risk of developing RA and may be present years before onset of clinical disease. The immune pathology leading to RA and RF may have similar genetic and environmental influences. OBJECTIVE: To measure RF in people for whom data on birth weight, infant growth, and markers of infectious exposure during infancy and childhood, had been previously recorded. METHODS: 675 men and 668 women aged 59-67 years, born and still resident in Hertfordshire, UK, were studied. RF was measured with an ELISA. Associations between presence of RF, early growth, and markers of hygiene in infancy, were investigated. RESULTS: RF was detected in 112/675 (16.6%) men and 79/668 (11.8%) women. No significant relationships existed between early growth and presence of RF in men or women. Among women, sharing a bedroom during childhood was associated with a lower risk of RF positivity (OR = 0.48, 95% CI 0.30 to 0.78, p = 0.003). CONCLUSIONS: A developing immune system exposed to increased infectious exposure is less likely to produce RF in adult life; this may reduce the pathological process which leads to RA.
18354225 Suppression of proteoglycan-induced arthritis by anti-CD20 B Cell depletion therapy is med 2008 Apr 1 B cells have been implicated in the pathogenesis of rheumatoid arthritis (RA) since the discovery of RA as an autoimmune disease. There is renewed interest in B cells in RA based on the clinical efficacy of B cell depletion therapy in RA patients. Although, reduced titers of rheumatoid factor and anti-cyclic citrullinated peptide Abs are recorded, the mechanisms that convey clinical improvement are incompletely understood. In the proteoglycan-induced arthritis (PGIA) mouse model of RA, we reported that Ag-specific B cells have two important functions in the development of arthritis. PG-specific B cells are required as autoantibody-producing cells as well as Ag-specific APCs. Herein we report on the effects of anti-CD20 mAb B cell depletion therapy in PGIA. Mice were sensitized to PG and treated with anti-CD20 Ab at a time when PG-specific autoantibodies and T cell activation were evident but before acute arthritis. In mice treated with anti-CD20 mAb, development of arthritis was significantly reduced in comparison to control mAb-treated mice. B cell depletion reduced the PG-specific autoantibody response. Furthermore, there was a significant reduction in the PG-specific CD4(+) T cell recall response as well as significantly fewer PG-specific CD4(+) T cells producing IFN-gamma and IL-17, but not IL-4. The reduction in PG-specific T cells was confirmed by the inability of CD4(+) T cells from B cell-depleted mice to adoptively transfer disease into SCID mice. Overall, B cell depletion during PGIA significantly reduced disease and inhibited both autoreactive B cell and T cell function.
18710589 High avidity autoreactive T cells with a low signalling capacity through the T-cell recept 2008 Self-reactive T cells with low signalling capacity through the T-cell receptor were recently observed in the SKG mouse model of rheumatoid arthritis (RA) and have been linked to a spontaneous mutation in the ZAP-70 signal transduction molecule. Here we hypothesize that similar mechanisms also drive RA, associated with an abnormal innate and adaptive immune response driven by nuclear factor-kappaB activation and tumour necrosis factor secretion. Similar to the essential role played by pathogens in SKG mice, we propose that HLA-associated immunity to chronic viral infection is a key factor in the immune dysregulation and joint inflammation that characterize RA.
17927490 Abatacept: a novel treatment for rheumatoid arthritis. 2007 Oct Rheumatoid arthritis (RA) is a chronic, autoimmune disease that has traditionally been treated with non-biologic and biologic disease-modifying antirheumatic drugs (DMARDs). Although these agents have become firmly established as effective RA treatments, some patients do not have an adequate response. The recent approval of abatacept, a first-in-class agent that selectively modulates the activation of T cells, offers an alternative therapeutic option. As reflected in pharmacokinetic analyses, abatacept 10 mg/kg has been shown to be effective in treating patients with established RA. Demonstrating safety, efficacy and quality of life improvements in a wide range of RA patients, including those with inadequate response to methotrexate or tumor necrosis factor antagonists, abatacept is seen as a valuable addition to the RA treatment armamentarium.
19091932 Social interactions in an online self-management program for rheumatoid arthritis. 2008 Dec OBJECTIVE: To evaluate social interactions among individuals with rheumatoid arthritis (RA), participating in an empirically based, cognitive-behavioural, self-management (SM), and peer-support program, delivered in an online format. METHODS: Thirty individuals with RA were recruited online. Subjects were a subset of participants in the treatment arm of a waiting-list controlled study testing the effectiveness of a 10-week, online, SM education and peer support program. Primary outcomes were process variables describing social activity in the online environment during active treatment. Qualitative review of discussion board posts was undertaken to gain insight into participants' perceptions of social interactions. RESULTS: Participants spent a large proportion of logged-in time accessing educational materials and community-level activity was vibrant, with members utilizing the discussion board and e-mail. The Chat feature was less well-used. Discussion board posts regarding RAHelp were very positive, especially in regard to perceived supportiveness and bonding among participants, and a sense of feeling uniquely understood by others who have RA. Concern arose in response to periods in which the discussion board was 'too quiet'. DISCUSSION: Our work complements the emerging literature supporting acceptance and utility of Internet-based programming as a venue for SM education and social interaction among individuals with chronic illness.
16204375 Plantar sensitivity, foot loading and walking pain in rheumatoid arthritis. 2006 Feb OBJECTIVE: The aim of the present study was to investigate the tactile sensitivity of the plantar surface in rheumatoid feet and its relationship to walking pain and plantar foot loading characteristics. METHODS: In 25 patients with rheumatoid arthritis (RA) and 21 healthy controls, Semmes-Weinstein monofilaments were used to assess tactile sensitivity in six foot regions. Walking pain was examined clinically. Pedography was used to analyse foot loading parameters during barefoot walking. RESULTS: In RA patients, plantar sensitivity was significantly decreased under all foot regions examined compared with the control group (P<0.05). A loss of protective sensation was found in a total of 10 regions in seven patients but not in the control group. In the RA patients, foot loading was reduced in the hindfoot (P<0.05) but was slightly increased in the forefoot (not significant). Average walking pain was 3.8 +/- 2.1 on a scale from 0 to 10 but did not correlate with the sensitivity levels. CONCLUSION: In patients with RA, no direct relationship between pain intensity and plantar foot loading was found. The decreased tactile sensitivity may be indicative of a disturbed sensation for high plantar pressures. Therefore, pedography can be useful as an additional tool in the detection of excessive forefoot loading before complications are manifested.
16840501 Polyarticular psoriatic arthritis is more like oligoarticular psoriatic arthritis, than rh 2007 Jan BACKGROUND: and objective: Since the original description of psoriatic arthritis (PsA) subgroups by Moll and Wright, there has been some discrepancy in the precise prevalence of the different subgroups and in particular the proportion of patients with polyarthritis. The higher prevalence of the polyarthritis subgroup may be due to the inclusion of patients with seronegative rheumatoid arthritis with coincidental psoriasis. The classification of psoriatic arthritis (CASPAR) study database provided an opportunity to examine this question. METHODS: The CASPAR study collected clinical, radiological and laboratory data on 588 patients with physician-diagnosed PsA and 525 controls with other inflammatory arthritis, 70% of whom had rheumatoid arthritis. Patients with PsA were divided into two groups: polyarthritis and non-polyarthritis (which included the Moll and Wright subgroups of spinal disease, distal interphalangeal predominant and arthritis mutilans) and were compared with patients with rheumatoid arthritis. Comparisons were made between all three groups and, if a significant difference occurred, between the two groups with PsA. RESULTS: The three groups differed significantly with regard to all clinical and laboratory variables except duration of disease. Significant differences were also found between the two groups of PsA in terms of age, sex, total number of involved joints, disability score and symmetry. However, no differences were found between the groups of patients with PsA in terms of seropositivity for rheumatoid factor and antibodies to cyclic citrullinated peptide, enthesitis, and spinal pain and stiffness. Further, dactylitis was commonly seen in patients with PsA (57% in the polyarticular group and 45% in non-polyarticular group), and uncommonly found in patients with rheumatoid arthritis (5%). With the exception of entheseal changes, syndesmophytes and osteolysis, typical radiological features of PsA could not be used to distinguish between the PsA subgroups. CONCLUSIONS: The evidence suggests that the changing prevalence of the polyarticular subgroup of PsA is not because doctors include patients with seronegative rheumatoid arthritis with coincidental psoriasis.
18200805 Atherogenic lipid profiles and its management in patients with rheumatoid arthritis. 2007 Cardiovascular morbidity and mortality are enhanced in rheumatoid arthritis, which might be due to an increased prevalence of cardiovascular risk factors such as dyslipidemia. The dyslipidemia observed in RA appears to be dependent on disease activity, ie, a higher disease activity is associated with lower total cholesterol levels and even more depressed high density lipoprotein levels, leading to a higher (ie, unfavorable) atherogenic index. It appears that this dyslipidemia is already present long before the clinical onset of rheumatoid arthritis. Antirheumatic drug treatment with disease modifying antirheumatic drugs as well TNF-blocking agents has, in general, favorable, albeit moderate, effects on the lipid profile. Therefore, it is unlikely that the observed beneficial effects of antirheumatic drug treatment on cardiovascular morbidity and cardiovascular mortality in rheumatoid arthritis is mediated through effects on the lipid metabolism. Management of dyslipidemia in rheumatoid arthritis should be part of a general cardiovascular risk management. Hence, in addition to the assessment of the lipid profile, other cardiovascular risk factors should be determined and appropriate treatment installed when indicated. Lower treatment thresholds should be considered in view of the enhanced cardiovascular risk in rheumatoid arthritis and guidelines should be developed based on epidemiological data.
19216454 [The synoviorthesis: a reappraisal]. 2008 Jun BACKGROUND: The evolution of the rheumatologic practice involved a handing-over in question of the place and methods of application of the synoviorthesis. The last innovations, in particular the appearance of the bio-therapies, allowed a better control of inflammatory rheumatism thus making it possible to better select arthritis likely to profit precociously from a synoviorthesis before the installation of major articular destruction. AIM: Through a general review of the literature, we recall in this work the various means of synoviorthesis, their current indications and their results. METHODS: An extensive electronic search of the relevant literature was carried out using MEDLINE. Key words used for the final search were: synoviorthesis, osmic acid, radiosynoviorthesis, arthritis, treatment. RESULTS: This systematic review allowed us to conclude that fields of application of the synoviorthesis is in addition widens because of the interesting results to see spectacular this technique in some other affections such as the haemophilia. In addition we have compared the efficiency and the tolerance of the different methods of synoviorthesis. CONCLUSION: The synoviorthesis constitutes a tempting therapeutic alternative of share its effectiveness and its good tolerance so much so that it constitutes an undeniable factor of articular protection. Its fields of application widened. Thus on the good knowledge of the indications and the precautions necessary to its realization its success.
17537367 [Antibodies to citrullinated peptides in rheumathoid arthritis]. 2007 May 5 Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic inflammation of the synovial joints leading to progressive joint destruction. The serum of these patients contains a large repertoire of autoantibodies, mainly rheumatoid factor, which is part of the ACR classification criteria in spite of having only moderate specificity. Antibodies directed to citrullinated proteins provide clinicians with a valuable tool for early diagnosis. It has been shown that these antibodies can be detected years before presentation of the first symptom and are very useful for diagnosis and prognosis, due to good sensitivity and specificity and prediction of development of erosive disease. The immune response against citrullinated antigens is characteristic of an immuno-genetic subtype of disease, in which the combined role of genes, environmental factors and autoimmunity has become the prime suspected for disease pathogenesis. A model is proposed of how these antibodies are produced and lead to chronic synovial inflammation.
17332703 [Classification of early arthritis patients and how to determine disease severity]. 2007 Feb Recent clinical studies of rheumatoid arthritis reveal that therapeutic intervention early in rheumatoid arthritis leads to less joint damage, indicating the importance of early diagnosis of RA for improvement of prognosis. According to the data of our "Early Arthritis Prospective Cohort", we have found that early arthritis patients, described as undifferentiated arthritis, progress to rheumatoid arthritis at high frequency if the patients positive with anti-cyclic citrullinated peptide antibody (anti-CCP antibody) and bone marrow edema at the entry. In addition, we are going to classify the pathologic status (disease severity) of early arthritis patients by serologic variables, radiographic findings and genetic analysis.
19091101 Lack of association between glucocorticoid use and presence of the metabolic syndrome in p 2008 INTRODUCTION: Rheumatoid arthritis (RA) associates with excessive cardiovascular morbidity and mortality, attributed to both traditional and novel cardiovascular risk factors. The metabolic syndrome, a cluster of classical cardiovascular risk factors, including hypertension, obesity, glucose intolerance, and dyslipidaemia, is highly prevalent in RA. Reports suggest that long-term glucocorticoid (GC) use may exacerbate individual cardiovascular risk factors, but there have been no studies in RA to assess whether it associates with the metabolic syndrome. We examined whether GC exposure associates with the presence of metabolic syndrome in patients with RA. METHODS: RA patients (n = 398) with detailed clinical and laboratory assessments were categorised into three groups according to GC exposure: no/limited (<3 months) exposure (NE), low-dose (<7.5 mg/day) long-term exposure (LE), and medium-dose (greater than or equal to 7.5 mg to 30 mg/day) long-term exposure (ME). The metabolic syndrome was defined using the National Cholesterol Education Programme III guidelines. The association of GC exposure with the metabolic syndrome was evaluated using binary logistic regression. RESULTS: The metabolic syndrome was present in 40.1% of this population and its prevalence did not differ significantly between the GC exposure groups (NE 37.9% versus LE 40.7% versus ME 50%, P = 0.241). Binary logistic regression did not demonstrate any increased odds for the metabolic syndrome when comparing ME with LE (odds ratio = 1.64, 95% confidence interval 0.92 to 2.92, P = 0.094) and remained non significant after adjusting for multiple potential confounders. CONCLUSIONS: Long-term GC exposure does not appear to associate with a higher prevalence of the metabolic syndrome in patients with RA. The components of the metabolic syndrome may already be extensively modified by other processes in RA (including chronic inflammation and treatments other than GCs), leaving little scope for additive effects of GCs.
18190880 Stress as a trigger of autoimmune disease. 2008 Jan The etiology of autoimmune diseases is multifactorial: genetic, environmental, hormonal, and immunological factors are all considered important in their development. Nevertheless, the onset of at least 50% of autoimmune disorders has been attributed to "unknown trigger factors". Physical and psychological stress has been implicated in the development of autoimmune disease, since numerous animal and human studies demonstrated the effect of sundry stressors on immune function. Moreover, many retrospective studies found that a high proportion (up to 80%) of patients reported uncommon emotional stress before disease onset. Unfortunately, not only does stress cause disease, but the disease itself also causes significant stress in the patients, creating a vicious cycle. Recent reviews discuss the possible role of psychological stress, and of the major stress-related hormones, in the pathogenesis of autoimmune disease. It is presumed that the stress-triggered neuroendocrine hormones lead to immune dysregulation, which ultimately results in autoimmune disease, by altering or amplifying cytokine production. The treatment of autoimmune disease should thus include stress management and behavioral intervention to prevent stress-related immune imbalance. Different stress reactions should be discussed with autoimmune patients, and obligatory questionnaires about trigger factors should include psychological stress in addition to infection, trauma, and other common triggers.
17849692 The effect of infliximab treatment on insulin resistance in patients with rheumatoid arthr 2007 Jul AIM: It is well known that increased insulin resistance is associated with the development of cardiovascular disease in patients with rheumatoid arthritis and that tumour necrosis factor-alpha plays an important role in this process. Infliximab is a chimeric monoclonal anti-tumour necrosis factor-alpha antibody. This study investigates the effects of long term infliximab treatment on insulin resistance in patients with rheumatoid arthritis. MATERIALS AND METHODS: Seven rheumatoid arthritis patients (6 female and 1 male; mean age: 44.6 +/- 12.3, mean duration of disease: 6.8 y) for whom infliximab treatment had been planned at the rheumatology and internal medicine clinics were included. Patients were evaluated during and at the end of the study with a mean follow-up duration of 9.6 months. Fasting plasma glucose, fasting plasma insulin levels and serum lipid profile were assessed at baseline and throughout the treatment period (prior to every infusion). Homeostasis Model Assessment of Insulin Resistance model was used for the assessment of insulin sensitivity. RESULTS: Fasting insulin and Homeostasis Mode Assessment of Insulin Resistance levels decreased after treatment (from 19.4 +/- 7.7 microU/ml to 8.9 +/- 4.1 microU/ml and from 2.4 +/- 1 to 1.1 +/- 0.5, respectively; p < 0.05 for both). No significant change was observed in other parameters. CONCLUSION: An improvement in insulin sensitivity was observed in patients receiving long term infliximab treatment for rheumatoid arthritis.