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ID PMID Title PublicationDate abstract
17845713 Association of the microsatellite in the 3' untranslated region of the CD154 gene with rhe 2007 CD40-CD154 interaction is an important mediator of inflammation and has been implicated in T helper type 1-mediated autoimmune diseases including rheumatoid arthritis (RA). Linkage studies have shown association of markers in the proximity of the CD154 gene. In the present work we investigated whether specific allele variants of the microsatellite in the 3' UTR of the CD154 gene might modulate the risk of RA. The study, in a case-control setting, included 189 patients and 150 healthy controls from the Canary Islands, Spain. The 24CAs allele was less represented in female patients than in controls (0.444 in controls versus 0.307 in patients, P = 0.006, odds ratio (OR) 0.556, 95% confidence interval (CI) 0.372 to 0.831) but not in males (0.414 versus 0.408), and only when homozygous (P = 0.012; OR 0.35, 95% CI 0.16 to 0.77). We also verified that CD154 association with RA was independent of human leukocyte antigen (HLA) phenotype. A further functional study showed that after stimulation anti-CD3, CD154 mRNA was more stable in CD4+ T lymphocytes from patients with RA bearing the 24CAs allele (mRNA half-life 208 minutes) than in patients without the 24CAs allele (109 minutes, P = 0.009). However, a lower percentage of CD154+CD4+ T lymphocytes was seen in freshly isolated peripheral blood mononuclear cells from patients carrying 24CAs alleles (mean 4.28 versus 8.12; P = 0.033), and also in CD4+ T lymphocytes stimulated with anti-CD3 (median 29.40 versus 47.60; P = 0.025). These results were concordant with the smaller amounts of CD154 mRNA isolated from stimulated T lymphocytes with 24CAs alleles. The CD154 microsatellite therefore seems to affect the expression of the gene in a complex manner that implies not only mRNA stability. These data suggest that the CD154 microsatellite contributes to the regulation of mRNA and protein expression, although further studies will be necessary to elucidate its role in disease predisposition.
17958026 [Role of the patients' associations (CLAIR consortium)]. 2007 Sep The Confederation Against Rheumatoid Inflammatory Diseases (CLAIR) is regrouping patients, doctors, paramedics, relatives and voluntaries, which are all members of the associations Lupus Erythematosus, Sclerodermia, Rheumatoid Arthritis and "Patient Partner Program". The purpose of the association are -to create a chain of solidarity, hope and listening between patients suffering from these diseases. At least one hundred thousand of people are concerned by these rheumatoid inflammatory diseases; -to make the general public aware of this range of chronic diseases; -to make the medical world aware of the importance of early diagnosis and rapid aggressive treatment; -to establish relationships with the political world in order to improve awareness and recognition, of chronic inflammatory diseases; -to support joint projects of the associations in order to promote medical research.
17075601 Interleukin 6: from bench to bedside. 2006 Nov Interleukin (IL)-6 is a pleiotropic cytokine that has important roles in the regulation of the immune response, inflammation, and hematopoiesis. Disruption of IL-6 regulation might, however, affect the immune response and consequently induce immune-mediated inflammatory diseases such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease, and Crohn's disease. Overproduction of IL-6 also contributes, through its roles as a growth factor or an antiapoptotic factor, to the development of malignant diseases such as multiple myeloma and renal cancer. Progress in the study of IL-6 has increased our understanding of the pathological roles of this cytokine in these diseases and provided key evidence that antagonizing its activities can be used as a therapeutic strategy. The application of molecular biology techniques to design monoclonal antibodies as therapeutic agents has made it possible to regulate the IL-6 signal to successfully treat diseases that have so far proved refractory to conventional therapies. Blocking IL-6 actions by use of a humanized antibody, tocilizumab, which targets the IL-6 receptor, has been proven to be therapeutically effective for rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease and Crohn's disease. In this review, we discuss a paradigm of IL-6 from basic science to clinical use.
16641044 Factors associated with hyperhomocysteinaemia in Mexican patients with rheumatoid arthriti 2006 Mar BACKGROUND: Hyperhomocysteinaemia is a factor related to the development of atherosclerosis in rheumatoid arthritis (RA). However, Hispanics with RA develop high rates of coronary disease; there are no studies about the frequency and factors related to high levels of homocysteine in Mexican patients. OBJECTIVE: To evaluate the prevalence and characteristics associated with hyperhomocysteinaemia in Mexican patients with RA. METHODS: One hundred and fifty-two patients with RA were compared with 153 controls. The assessment in RA included clinical characteristics, disease activity (RADAR), functioning (HAQ-Di and global functional status), comorbidity, and radiological damage. Laboratory determinations included total serum homocysteine (tHcy), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and lipid profile. RESULTS: Median levels of homocysteine were higher in RA compared with controls (11.3 vs. 9.3, p<0.001). Twenty per cent of the patients with RA had hyperhomocysteinaemia (>15 micromol/L) compared with 6% in controls (p<0.001). There was statistical association between hyperhomocysteinaemia in RA with male gender (p<0.001), impairment in the global functional status (p = 0.004), higher radiological damage (p = 0.001), and CRP (p = 0.04). There was no association with RADAR, HAQ-Di, or RF, methotrexate dose or duration of use. In the adjusted multivariate model, the two variables associated with higher risk for hyperhomocysteinaemia were male gender (OR = 4.2, 95% CI 2 to 12, p = 0.006) and higher radiological damage (III-IV) (OR = 3.4, 95% CI 1.3 to 9, p = 0.01). CONCLUSIONS: Our data show a high prevalence of hyperhomocysteinaemia in Mexican patients with RA. More effort is required to evaluate and treat earlier this coronary risk factor.
17594488 Constitutive upregulation of the transforming growth factor-beta pathway in rheumatoid art 2007 Genome-wide gene expression was comparatively investigated in early-passage rheumatoid arthritis (RA) and osteoarthritis (OA) synovial fibroblasts (SFBs; n = 6 each) using oligonucleotide microarrays; mRNA/protein data were validated by quantitative PCR (qPCR) and western blotting and immunohistochemistry, respectively. Gene set enrichment analysis (GSEA) of the microarray data suggested constitutive upregulation of components of the transforming growth factor (TGF)-beta pathway in RA SFBs, with 2 hits in the top 30 regulated pathways. The growth factor TGF-beta1, its receptor TGFBR1, the TGF-beta binding proteins LTBP1/2, the TGF-beta-releasing thrombospondin 1 (THBS1), the negative effector SkiL, and the smad-associated molecule SARA were upregulated in RA SFBs compared to OA SFBs, whereas TGF-beta2 was downregulated. Upregulation of TGF-beta1 and THBS1 mRNA (both positively correlated with clinical markers of disease activity/severity) and downregulation of TGF-beta2 mRNA in RA SFBs were confirmed by qPCR. TGFBR1 mRNA (only numerically upregulated in RA SFBs) and SkiL mRNA were not differentially expressed. At the protein level, TGF-beta1 showed a slightly higher expression, and the signal-transducing TGFBR1 and the TGF-beta-activating THBS1 a significantly higher expression in RA SFBs than in OA SFBs. Consistent with the upregulated TGF-beta pathway in RA SFBs, stimulation with TGF-beta1 resulted in a significantly enhanced expression of matrix-metalloproteinase (MMP)-11 mRNA and protein in RA SFBs, but not in OA SFBs. In conclusion, RA SFBs show broad, constitutive alterations of the TGF-beta pathway. The abundance of TGF-beta, in conjunction with an augmented mRNA and/or protein expression of TGF-beta-releasing THBS1 and TGFBR1, suggests a pathogenetic role of TGF-beta-induced effects on SFBs in RA, for example, the augmentation of MMP-mediated matrix degradation/remodeling.
17434144 siRNA targeting PLK-1 induces apoptosis of synoviocytes in rheumatoid arthritis. 2007 Jun 1 Polo-like kinase-1 (PLK-1) is a member of the PLK family and participates in the control of cell mitosis. Here, we show that immunoreactive PLK-1 is strongly expressed in synoviocytes and some infiltrative mononuclear cells in synovial tissues from patients with rheumatoid arthritis (RA), while patients with osteoarthritis and injury show little or no expression of PLK-1 in synovial tissues. Western blot analysis shows that PLK is expressed and its expression is enhanced by IL-1beta in RA synoviocytes. IL-1beta also enhanced the cell growth of RA synoviocytes. Moreover, siRNA targeted against PLK-1 significantly decreases the expression of PLK-1 of RA synoviocytes stimulated by IL-1beta and suppresses the proliferation of these synoviocytes through apoptosis. These findings suggest that PLK-1 plays a critical role in the proliferation of RA synoviocytes leading to bone destruction, and siRNA against PLK-1 is potentially useful for the treatment of RA.
18634159 Predictors of discontinuation of tumor necrosis factor inhibitors in patients with rheumat 2008 Sep OBJECTIVE: Tumor necrosis factor-alpha (TNF) inhibitors have transformed management of rheumatoid arthritis (RA); however, many patients discontinue TNF inhibitors. Our goal was to determine the discontinuation rate of TNF inhibitors and identify predictors associated with discontinuation. METHODS: Enrollees in the Brigham RA Sequential Study (BRASS) formed the eligible cohort. Patients reporting use of a TNF inhibitor with at least 6 months of followup were followed until reporting TNF inhibitor discontinuation or their last study visit if they continued therapy. Potential predictor variables, including demographic and clinical data assessed at baseline and 6 months prior to study endpoint, were identified using a Cox proportional regression. RESULTS: Among 961 patients in BRASS, 503 were using a TNF inhibitor with at least 6 months of followup in BRASS (mean length of followup 39 mo, SD 13). Two hundred ten patients (42%) reported discontinuation of TNF inhibitor. Higher physician global scores (hazard ratio 1.27, 95% CI 1.18-1.38) and RA Disease Activity Index scores (HR 1.13, 95% CI 1.05-1.22) 6 months prior to stopping the TNF inhibitor and higher number of TNF inhibitors used previously (HR 1.30, 95% CI 1.03-1.66) were associated with discontinuation of TNF inhibitor. Prior use of synthetic disease modifying antirheumatic drugs (HR 0.50, 95% CI 0.34-0.72) and more years of cumulative methotrexate use (HR 0.24, 95% CI 0.12-0.47) were inversely associated with discontinuation of TNF inhibitor. CONCLUSION: These data demonstrate that a significant number of patients with RA discontinue TNF inhibitors. Several easily characterized clinical variables have a modest predictive association with reduced probability of TNF inhibitor discontinuation.
18179735 The incidence and prevalence of extra-articular and systemic manifestations in a cohort of 2008 Feb OBJECTIVE: To evaluate the incidence and prevalence of extra-articular (ExRA) and systemic (SysM) manifestations in a cohort of newly-diagnosed patients with rheumatoid arthritis (RA) in the United States. PATIENTS AND METHODS: Retrospective analysis using inpatient, outpatient, and pharmacy claims data contained in the Thomson Healthcare MarketScan research databases. Patients >or= 18 years of age with a diagnosis of RA (ICD-9-CM 714.0x) on three non-diagnostic claims on different days between January 1, 1999 and September 30, 2006, and at least 12 months of continuous enrollment prior to, and at least 2 years following diagnosis were included in the analysis. Thirty ExRA/SysM, classified into six groups (cardiovascular, blood, mucosa, pulmonary, other, and non-specific), were evaluated. Patients were followed until in-hospital death, disenrollment, or study end. RESULTS: A total of 16,752 patients were included (mean age 59.8 +/- 13.5 years; 72.0% female), and were followed up for a mean of 3.9 +/- 1.4 years. ExRA/SysM were experienced by 47.5% of patients, with cardiovascular (27.2%) the most common. The most frequent individual ExRA/SysM was 'other CVD' (17.2%). Female sex was associated with a reduced risk of cardiovascular ExRA/SysM (HR, 0.66; 95% CI, 0.61-0.72), and an increase in mucosa ExRA/SysM (HR, 2.55; 95% CI, 2.03-3.19). Prior treatment with methotrexate (MTX) was associated with significantly reduced risks of cardiovascular (HR 0.65; 95% CI, 0.59-0.72) and blood system (HR 0.71; 95% CI, 0.61-0.82) ExRA/SysM. Other significant associations were also evident: age, comorbidity as measured by CCI and CDS, and geographic region were associated with increased risks for some ExRA/SysM, while prior NSAID treatment and the presence of diabetes were associated with a lower risk for some ExRA/SysM. CONCLUSION: ExRA/SysM develop in approximately 47% of patients with RA within a few years of diagnosis. Prior treatment with some therapies used in RA management were associated with a reduced risk of developing some ExRA/SysM, while several demographic factors and the presence of comorbidities also affected the risk of developing ExRA/SysM. This analysis was restricted to patients with employer- or government-funded health insurance, while several potential predictors of ExRA/SysM could not be controlled for in the multivariate analysis, as they could not be measured using claims data. Hence, these results may not be generalizable to other groups of patients with RA.
18726101 Circulating E-selectin and tumor necrosis factor-alpha in extraarticular involvement and j 2009 Jan In this cross-sectional study, we assessed the relationship between circulating TNF-alpha and E-selectin (sE-selectin) with extraarticular involvement and severity of joint disease in RA. We compared 56 patients who had RA and extraarticular involvement (ExRA) with a group of 84 patients with only articular involvement (non-ExRA). ExRA had higher circulating TNF-alpha than non-ExRA (32 +/- 9 vs. 28 +/- 6 pg/mL, P = 0.002). sE-selectin levels did not differ between both groups. sE-selectin correlated with tender joint count (rho = 0.19, P = 0.03), morning stiffness (rho = 0.19, P = 0.03), severity of pain (rho = 0.21, P = 0.02), disease activity (assessed by the patient) (rho = 0.21, P = 0.02), HAQ-DI (rho = 0.29, P = 0.004), and rheumatoid factor titers (rho = 0.31, P = <0.001). Circulating TNF-alpha had no correlation with sE-selectin or disease activity. We concluded that sE-selectin correlated with severity of joint disease, further follow-up studies should evaluate if sE-selectin is useful as prognosis marker for progression of articular damage.
18050184 The risk of herpes zoster in patients with rheumatoid arthritis in the United States and t 2007 Dec 15 OBJECTIVE: To determine whether the incidence of herpes zoster is elevated in patients with rheumatoid arthritis (RA) and whether herpes zoster is associated with use of disease-modifying antirheumatic drugs (DMARDs) in patients with RA. METHODS: Two retrospective cohort studies were conducted using data from a US integrated managed care database (PharMetrics claims database) from 1998-2002 and the UK General Practice Research Database (GPRD) between 1990-2001. Rates of herpes zoster among patients with RA and randomly sampled non-RA patients were compared. A nested case-control analysis was performed within each RA cohort to examine the effect of current treatment on herpes zoster risk. RESULTS: A total of 122,272 patients with RA from the PharMetrics database and 38,621 from the GPRD were included. The adjusted hazard ratios of herpes zoster for patients with RA compared with non-RA patients were 1.91 (95% confidence interval [95% CI] 1.80-2.03) in the PharMetrics database and 1.65 (95% CI 1.57-1.75) in the GPRD. In the PharMetrics database, current use of biologic DMARDs alone was associated with herpes zoster (odds ratio [OR] 1.54, 95% CI 1.04-2.29), as was current use of traditional DMARDs alone (OR 1.37, 95% CI 1.18-1.59). In the GPRD, current use of traditional DMARDs was associated with herpes zoster (OR 1.27, 95% CI 1.10-1.48). In both data sources, use of oral corticosteroids was associated with herpes zoster regardless of concomitant therapies. CONCLUSION: Data from 2 large databases suggested that patients with RA are at increased risk of herpes zoster. Among patients with RA, DMARDs and/or use of oral corticosteroids appeared to be associated with herpes zoster.
17965124 A high body mass index has a protective effect on the amount of joint destruction in small 2008 Jun BACKGROUND: Obesity is a state of chronic low-grade inflammation that predisposes people to several diseases and that is increasingly prevalent. Rheumatoid arthritis (RA) is marked by the presence of proinflammatory cytokines and, in general, the presence of high levels of inflammatory markers is associated with a severe disease course and joint damage. OBJECTIVES: To evaluate prospectively (a) whether obesity is a risk factor for the development of RA and (b) whether the body mass index (BMI) is associated with the amount of joint destruction in early RA after 3 years' follow-up. METHODS: In a cohort of 570 patients with undifferentiated arthritis, the relation between the BMI and the development of RA during 1 year of follow-up was assessed. In a cohort of 488 patients with early RA the correlation between the BMI and degree of radiological joint destruction (Sharp-van der Heijde score) after 3 years of follow-up was determined. The findings were replicated in an independent cohort of 247 patients with early RA. RESULTS: Obesity did not influence the likelihood of developing RA. In both RA cohorts, the BMI was inversely correlated with the Sharp-van der Heijde score after 3 years' follow-up (r = -0.15, p = 0.025 for the Leiden EAC and r = -0.27, p<0.001 for the replication cohort). Linear regression analyses in both cohorts showed that the BMI was independently and inversely associated with the level of joint destruction in anti-CCP-positive patients with RA, but not in anti-CCP-negative patients. CONCLUSIONS: A high BMI is associated with a less severe disease outcome in anti-CCP-positive patients with RA.
17139663 Osteoporosis management in patients with rheumatoid arthritis: Evidence for improvement. 2006 Dec 15 OBJECTIVE: Osteoporosis in patients with rheumatoid arthritis (RA) is increasingly recognized as a major comorbidity. We examined past management patterns for glucocorticoid-induced osteoporosis and attempted to improve care through an educational intervention. The goal was to examine the frequency of osteoporosis management in patients with RA treated at a large academic rheumatology practice. METHODS: We performed a structured chart review on randomly selected patients seen during 2004 for RA. Osteoporosis management was defined as a bone mineral density test or receipt of a medication for osteoporosis in the prior 24 months. The frequency of osteoporosis management among our study group was assessed. We also examined how glucocorticoid dosage affected osteoporosis management in adjusted models. RESULTS: We reviewed the records for 193 patients, 99 had not used glucocorticoids in the prior 24 months, and 94 had used them. Of the total study population, 48% had received a bone mineral density test or medication for osteoporosis. Some form of osteoporosis management was present for 64% of patients taking > or =5 mg prednisone for > or =3 months compared with 38% for patients taking none (P = 0.002). Predictors of osteoporosis management included older age, female sex, glucocorticoid dosage, and prior osteoporosis diagnosis or fracture. CONCLUSION: The frequency of osteoporosis management appears to have increased compared with a prior chart review.
18850260 Phenotypic characterization and invasive properties of synovial fluid-derived adherent cel 2008 Dec The present study aimed at characterizing the phenotype and functions of adherent synovial fluid (SF) cells derived from rheumatoid arthritis (RA), comparing with fibroblast-like synoviocytes (FLS) derived from RA synovial tissue (ST). Adherent SF-derived cells were spindle-shaped from passages 1-6 under light microscopy. The cell surface marker profile in SF-derived cells from passage 1-6 was similar to that of ST-derived FLS. Levels of MMP-1 and MMP-3 were not significantly different between SF-derived cells and ST-derived FLS (p = 0.20 and p = 0.40, respectively). There was no significant difference in the optical density value between two cell types in the cell invasion assay (p = 0.10). SF-derived adherent cells have a fibroblast-like phenotype from very early culture passages and have the potential to produce MMPs with the invasive capacity to degrade cartilage, identical to ST-derived FLS. Therefore, these cells could substitute for ST-derived FLS in studying the pathogenesis of RA.
17013609 Role of amyloidosis in determining the prognosis of dialyzed patients with rheumatoid arth 2007 Feb The role of secondary amyloidosis in determining the prognosis of dialyzed patients with rheumatoid arthritis (RA) was examined in 22 patients with a mean age of 60.1 years included 21 renal amyloidosis. RA duration until the start of dialysis was 19.5 +/- 7.2 years and the observation period after introduction 27.1 +/- 26.4 months. Of the 14 dead cases, four died due to sepsis, three due to gastrointestinal tract bleeding, two due to congestive heart failure, and eight cases died within 5 months after starting dialysis. When comparing the eight survivors and the nine non-survivors who died within 2 years after the start of dialysis, the former patients showed significantly higher serum albumin, and lower electrocardiogram score and cardiothoracic ratios at the time of introduction to dialysis. The careful prevention and treatment of infection, cerebrovascular and/or gastrointestinal tract complications seem to be necessary to improve the prognosis of RA patients after the initiation of renal replacement therapy.
17605011 Microvascular dysfunction in rheumatoid arthritis assessed by laser Doppler anemometry: re 2007 Dec In search of a noninvasive diagnostic test for rheumatoid vasculitis (RV), this study addressed the questions whether changes in capillary blood cell velocity (CBV) detected by laser Doppler anemometry in patients with rheumatoid arthritis (RA) were correlated with the levels of soluble adhesion molecules and whether cutaneous flow abnormalities may reflect extraarticular manifestations in RA. In 31 RA patients and 20 patients with osteoarthritis (OA), CBV was measured in the skin above the left ring finger at rest and after 3-min arterial occlusion. Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and soluble P-selectin (sP-selectin) were assessed by enzyme linked immunosorbent assay. Peak CBV was reduced in RA patients compared to OA patients (0.42 +/- 0.07 mm/s vs. 0.70 +/- 0.13 mm/s; P = 0.013). Both CBV during rest and reactive hyperemia were not correlated with the levels of soluble adhesion molecules. There were no significant differences in resting or peak CBV between RA patients with or without extraarticular manifestations. The lack of an inverse correlation between the levels of soluble adhesion molecules and CBV during rest and reactive hyperemia contradicts the assumption that inflammatory vascular damage indicated by increased levels of soluble adhesion molecules was the main reason for the impairment of microcirculation. The present results do not suggest that cutaneous flow abnormalities may reflect extraarticular manifestations in RA.
16572289 Bcl-x(L) expression in vivo in rheumatoid synovium. 2006 Nov To examine the expression of the apoptosis regulatory protein, Bcl-x(L), in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunohistochemistry for Bcl-x(L) was carried out on synovial samples from patients with RA and OA. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis were performed to qualitatively examine the expression of Bcl-x(L). Bcl-x(L) expression was detected in the lining, endothelium and inflammatory cells of both RA (n=20) and OA (n=10) samples. However, there was significantly more expression in the lining of RA synovium compared to OA (77 vs 61%, p<0.05). Many of the positive cells in the RA subsynovium were noted to be plasma cells. There was a significant correlation between Bcl-x(L) expression and the number of inflammatory cells in the subsynovium of RA and OA patients (r (s)=0.376, p<0.05, n=30). Age and disease duration did not correlate with Bcl-x(L) expression in rheumatoid patients. Bcl-x(L) may play a role in the extended survival of synoviocytes and inflammatory cells in rheumatoid synovium.
17907232 The importance of the disease process and disease-modifying antirheumatic drug treatment i 2007 Oct 15 OBJECTIVE: To evaluate the effect of disease-modifying antirheumatic drugs (DMARDs) on the likelihood of patients with rheumatoid arthritis (RA) developing septic arthritis (SA). METHODS: The United Kingdom General Practice Research Database (GPRD) was used to identify adults with RA, and age-, sex-, and practice-matched control subjects. Subjects were studied between 1987 and 2002. The risk of developing SA (excluding infected joint replacements) for individuals with RA was calculated and the effect of DMARD use determined. RESULTS: A total of 136,977 subjects (34,250 patients with RA, 102,747 controls) were identified. SA was identified in 345 subjects, of which 321 (236 in patients with RA, 85 in controls) cases occurred during the study period. The incidence rate of SA was 12.9 times higher in subjects with RA than in those without (95% confidence interval [95% CI] 10.1-16.5, P < 0.001). The incident rate ratios (IRRs) for developing SA while receiving DMARDs compared with receiving no DMARDs were different for different medications. Penicillamine (adjusted IRR 2.51, 95% CI 1.29-4.89, P = 0.004), sulfasalazine (adjusted IRR 1.74, 95% CI 1.04-2.91, P = 0.03), and prednisolone (adjusted IRR 2.94, 95% CI 1.93-4.46, P < 0.001) were associated with an increased incidence of SA when compared with not receiving any DMARD. The use of other DMARDs including methotrexate showed no such effect. CONCLUSION: Individuals with RA have an increased risk of developing SA. This increased risk can be attributed to both the disease process and the use of DMARDs.
17410320 Anti-CCP antibodies have more diagnostic impact than rheumatoid factor (RF) in a populatio 2007 Nov To compare the diagnostic powers of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) in a population selected for its high statistical relevance, over a 6-month period, an informed consent to test for anti-CCP was obtained from 1,025 consecutive patients for whom RF was ordered at a University laboratory. Within 1 year, a diagnosis was obtained without informing the physician about the anti-CCP result. Extensive statistical analyses were performed. A total of 768 patients satisfied the inclusion criteria, and 132 were classified as having RA, yielding a pre-test probability of RA of 17%. The sensitivities for anti-CCP and RF were 62 and 64% (P = 0.83), and the specificities were 97 and 90% (P < 0.001), respectively. The positive predictive value (PPV) was 79% for anti-CCP and 56% for RF (P < 0.001), whereas the negative predictive value was 92% for both. The likelihood ratio (LR) was 17.9 for anti-CCP and 6.2 for RF (P < 0.005). Forty RA patients were diagnosed with RA of less than 2 years length, and the same significant statistic differences between anti-CCP and RF were observed. Placing the results of both tests together, or using different cutoff points, increased the diagnostic utility of the tests. The anti-CCP test has statistically shown significant higher specificity, PPV, and LR for RA than the RF test in a clinically diverse population. If new criteria are to be devised to help diagnose early RA, anti-CCP should be included because it has a greater diagnostic impact than RF.
18254519 Complementary and alternative medicine use in rheumatoid arthritis: an audit of patients v 2007 Sep BACKGROUND: Complementary and alternative medicine (CAM) enjoys widespread popularity in chronic illnesses such as rheumatic diseases. Rheumatoid arthritis (RA) is the commonest inflammatory joint disease seen in clinical practice. No systematic study on the use of CAM by patients with RA is available from northern India. METHODS: We evaluated the prevalence and usage characteristics of CAM in Indian patients with RA using a questionnaire at a tertiary care centre in northern India. RESULTS: Of the 102 patients with RA included in the study, 39% reported current CAM use. As many as 84 respondents (82%) reported having tried CAM during the course of their disease. A total of 215 CAM courses were used, out of which 77 were being continued. Ayurveda was the commonest (28% courses) followed by homoeopathy (20%), yoga asana (17%) and pranayama (12%). Pain control was the primary reason for using CAM (69% of users). Most CAM therapies (78%) were started on the advice of friends and relatives. Discontinuation of CAM was attributed to lack of clinical benefit (78%) and adverse effects (10%). Of the patients using CAM, 87% did not reveal its use to their physicians, primarily because the physician did not enquire about it. CONCLUSION: Patients with RA frequently use CAM for pain control. These practices are often not revealed to the treating physician. Knowledge of the concurrent use of CAM may serve to alert the physician about potential side-effects or drug interactions.
16453283 CD28-dependent differentiation into the effector/memory phenotype is essential for inducti 2006 Feb OBJECTIVE: Interleukin-1 receptor antagonist (IL-1Ra)-deficient mice on a BALB/c background spontaneously develop a chronic inflammatory polyarthropathy closely resembling that of rheumatoid arthritis in humans. To elucidate the role of CD28 costimulatory signals in the development of this disease, we studied IL-1Ra/CD28-double-deficient mice. METHODS: We crossed IL-1Ra-deficient mice with CD28-deficient mice and observed the incidence and severity of arthritis. To investigate functions of IL-1Ra/CD28-double-deficient T cells, cells were stimulated with CD3 monoclonal antibody or allogeneic antigen-presenting cells (APCs) and their proliferative responses and levels of cytokine production were measured. RESULTS: Disease severity was lower in IL-1Ra/CD28-double-deficient mice than in mice that were deficient only in IL-1Ra, although incidence of arthritis was not affected by the presence or absence of CD28. When pathogenic IL-1Ra-KO T cells were transferred into nude mice, severe arthritis developed. Even though T cells from double-deficient mice showed the same diminished proliferative capacity as was seen in T cells from CD28-single-deficient animals, nude mice into which double-deficient T cells were transferred never developed arthritis. CONCLUSION: These findings indicate that IL-1Ra/CD28-double-deficient T cells can be activated by IL-1Ra-deficient activated APCs, resulting in induction of arthritis; however, these T cells did not induce the disease under normal conditions, because they did not differentiate into effector/memory phenotype.