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ID PMID Title PublicationDate abstract
18006540 Serum IgG antibodies to peptidylarginine deiminase 4 in rheumatoid arthritis and associati 2008 Mar BACKGROUND: Antibodies targeting citrullinated antigens are specific for rheumatoid arthritis (RA). Citrullination is catalysed by the peptidylarginine deiminase (PAD) enzyme family. Critical enzymes are often targeted by disease-specific antibodies in complex immune-mediated diseases. Here, we have tested for autoantibodies against human recombinant PAD4 (hPAD4) in Caucasian RA patients. METHODS: A time-resolved fluorometric immunoassay based on hPAD4 was developed to analyse sera from two RA cohorts (n = 237 and n = 177), one systemic lupus erythaematosus (SLE) cohort (n = 84) and 148 healthy controls. Simple and multiple analyses were performed to examine possible associations between anti-hPAD4 and disease variables. RESULTS: Raised levels of anti-hPAD4 IgG were found in both RA cohorts compared to the controls, and 23% of the RA patients were anti-hPAD4 IgG positive. Anti-hPAD4 was associated with anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF), as well as increased physical disability. Anti-hPAD4 was also associated with higher longitudinal radiographic damage scores and increased clinical joint pathology, but weaker than anti-CCP. No associations were found between anti-hPAD4 and selected Human leukocyte antigen (HLA)-DRB1 variants. CONCLUSIONS: Approximately 23% of Caucasian RA patients have serum IgG antibodies against hPAD4. The presence of serum anti-hPAD4 IgG was in simple analyses associated with a more severe disease phenotype, and the association with physical disability was maintained in multiple analyses.
18666028 Anti-CCP2 is an adjunct to, not a surrogate for, rheumatoid factor in the diagnosis of rhe 2008 Sep OBJECTIVES: To examine the diagnostic utility of the second generation of anti-cyclic citrullinated peptide (anti-CCP2) antibodies versus rheumatoid factor (RF) in rheumatoid arthritis (RA), and to study the association between anti-CCP2 and RA disease parameters. METHODS: Fifty consecutive Egyptian patients with RA, 37 patients with other rheumatic diseases, and 10 healthy controls were recruited for testing for anti-CCP2 and immunoglobulin M (IgM) rheumatoid factor (RF). Assessment measures included the Disease Activity Score (DAS28) for disease activity, the Health Assessment Questionnaire - Disability Index (HAQ-DI) for disability and the Short Erosion Narrowing Score (SENS) for radiological damage. RESULTS: The sensitivities of anti-CCP2 and IgM-RF in RA patients were 70% and 52%, with specificities of 91.5% and 89.4%, respectively. There was 73.2% agreement between anti-CCP2 and RF for all groups tested (kappa = 0.42, p<0.001) but agreement was only 66% for RA patients (kappa = 0.31, p<0.05). Anti-CCP2 had superior diagnostic properties [sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)] than RF, but using both RF and anti-CCP2 enhanced the sensitivity to 78%, when either test was positive, and the specificity to 100%, with a PPV of 1, when both tests were positive. Anti-CCP2 titre was significantly correlated with disease severity [rheumatoid nodules, rheumatoid factor (RF), and radiological damage] and HAQ-DI (p<0.05) but not with parameters of disease activity. CONCLUSION: Anti-CCP2 has superior diagnostic and prognostic properties in RA compared with RF. It should not replace RF as a serological test; however, since using both tests modestly increases sensitivity and markedly enhances specificity, so that diagnosis of RA is highly probable when both tests are positive.
17937476 Intracellular oxidative activation in synovial fluid neutrophils from patients with rheuma 2007 Nov OBJECTIVE: To compare total and intracellular oxidative activation of blood and synovial fluid (SF) neutrophils from patients with rheumatoid arthritis (RA) and other arthritides with blood donor neutrophils. METHODS: Peripheral blood and SF samples were obtained from 26 gonarthritis patients (13 RA, 13 non-RA) attending the rheumatology unit for therapeutic joint aspiration. Isolated neutrophils were stimulated by a formylated tripeptide (fMLF) or by microbeads coated with collagen-I. Formation of superoxide-anion-derived reactive oxygen species (ROS) was studied by luminol-enhanced chemiluminescence. Paired samples of blood and SF neutrophils from patients with active arthritis were compared with blood neutrophils from patients in remission and from 47 healthy blood donors. RESULTS: SF neutrophils from patients with RA, but not from non-RA patients, showed high baseline intracellular ROS production. Blood neutrophils from arthritis patients in remission existed in a primed state as revealed by more rapid oxidative response after collagen-bead challenge and a more pronounced response after fMLF stimulation compared to healthy blood donors. Blood neutrophils from RA patients with ongoing gonarthritis, however, did not differ from healthy blood donors concerning oxidative activation, whereas blood neutrophils from non-RA patients with gonarthritis showed a significantly lower peak ROS production. CONCLUSIONS: A novel finding with pathogenetic implications in our study is that SF neutrophils from patients with RA, but not other arthritides, are activated and produce ROS intracellularly. This implies that synovial neutrophils in RA are engaged in the processing of endocytosed material.
18708934 Is rheumatoid arthritis a risk factor for a high-riding vertebral artery? 2008 Aug 15 STUDY DESIGN: A retrospective comparative study on the morphologic characteristics of the axis in patients with or without rheumatoid arthritis (RA). OBJECTIVE: To compare the morphologic risk of vertebral artery (VA) injury during atlantoaxial transarticular screw fixation between patients with or without RA. SUMMARY OF BACKGROUND DATA: VA injury is a potentially serious complication during atlantoaxial transarticular screw fixation. Although this operation is frequently performed on RA patients, there have been few comparative studies on the morphologic risk of VA injury between RA and non-RA patients. METHODS: A total of 107 three-dimensional computed tomography images of the cervical spine including the C1-C2 complex were evaluated. Forty-seven RA patients and 60 non-RA patients were included in the study. The maximum atlantoaxial transarticular screw diameter (MSD) that could be inserted without breaching the cortex was measured 3-dimensionally using a computer- assisted navigation system. A high-riding-VA carrier was defined as a patient with either MSD of 4 mm or less. In RA patients, the space available for the spinal cord in flexion (SAC in flexion), duration of disease, RA stage, and type of disease were examined. RESULTS: In the RA group, 45 of 94 MSDs (47.9%) were 4 mm or less, and 33 of 47 patients (70.2%) were high-riding-VA carriers. In the non-RA group, 11 of 120 MSDs (9.2%) were 4 mm or less, and 9 of 60 (15.0%) patients were high-riding-VA carriers. MSD, C3 A-P diameter, and the ratio of MSD to C3 A-P diameter were significantly smaller in the RA group than in the non-RA group. Multiple logistic regression analysis showed that SAC in flexion was a significant risk factor for a high-riding-VA carrier in the RA group. CONCLUSION: RA was a significant risk factor for the presence of a high-riding VA. When performing atlantoaxial transarticular screw fixation, particularly on RA patients, thorough preoperative evaluation of the bony architecture is of great importance to avoid inadvertent VA injury.
17562093 Polymorphism in the tumor necrosis factor-alpha gene promoter is associated with severity 2008 Jan Rheumatoid arthritis (RA) is a model of multigenic inflammatory disorder in which tumor necrosis factor-alpha (TNF-alpha) plays an important role. Genetic factors may be implicated in the susceptibility to disease initiation as well as in severity of disease course. Elevated levels of TNF-alpha in the plasma and synovial fluid from RA patients may be associated with polymorphisms in the promoter region of the TNF-alpha gene. The aim of this study was to elucidate putative association between the -308 G/A polymorphism in the promoter region of the TNF-alpha gene and susceptibility to onset and severity of RA. A total of 130 RA patients and a control group of 150 healthy subjects with similar age and sex distribution were available for the study. All patients fulfilled the American College of Rheumatology revised criteria for RA. RA patients had a disease duration of at least 2 years. Radiographs of both hands of all RA patients were scored with the Steinbrocker method. There were 15 patients of stage I (nonerosive form) of RA and 114 patients of stages II-IV (erosive form). To assess the RA patient's functional ability, the Health Assessment Questionnaire (HAQ) was used. The -308 G/A promoter polymorphism of the TNF-alpha gene was detected by polymerase chain reaction and restriction fragment length polymorphism analysis. No differences in genotype distribution and allelic frequences of -308 G/A TNF-alpha promoter polymorphism have been found between RA patients and the control group. Significant differences have been observed within the RA group divided according to the radiographic progression of disease based on the Steinbrocker radiographic score and functional ability (HAQ). These results suggest an association of the -308 G/A polymorphism of the TNF-alpha gene with the severity of RA.
17922685 Increased expression of soluble form of vascular cell adhesion molecule-1 aggravates autoi 2007 Nov Vascular cell adhesion molecule-1 (VCAM-1, CD106) is important in leukocyte trafficking and its increased expression is associated with a number of chronic inflammatory diseases, including rheumatoid arthritis (RA). A soluble form of VCAM-1 (sVCAM-1) is generated by shedding of the membrane-bound molecule. The concentration of sVCAM-1 is increased in the sera of RA patients, but its pathological role has not been elucidated. The effect of sVCAM-1 relative to protection or aggravation of disease on the development of spontaneous arthritis was examined in an animal model of RA, namely MRL-Fas(lpr) mice (which display a disease resembling human RA), by generation of sVCAM-1 transgenic MRL-Fas(lpr) mice. Transgenic MRL-Fas(lpr) mice that expressed sVCAM-1 had higher incidence and increased severity of arthritis associated with higher levels of serum IgG rheumatoid factor compared with non-transgenic MRL-Fas(lpr) mice. These results suggest that sVCAM-1 plays an arthritogenic role in the development of inflammatory arthritis in MRL-Fas(lpr) mice and may present an important target for therapeutic strategy of RA.
16966729 Benefit design and specialty drug use. 2006 Sep In this paper we examine spending by privately insured patients with four conditions often treated with specialty drugs: cancer, kidney disease, rheumatoid arthritis, and multiple sclerosis. Despite having employer-sponsored health insurance, these patients face substantial risk for high out-of-pocket spending. In contrast to traditional pharmaceuticals, we find that specialty drug use is largely insensitive to cost sharing, with price elasticities ranging from 0.01 to 0.21. Given the expense of many specialty drugs, care management should focus on making sure that patients who will most benefit receive them. Once such patients are identified, it makes little economic sense to limit coverage.
17083760 Can remission be maintained with or without further drug therapy in rheumatoid arthritis? 2006 Nov Remission is now the accepted goal of management in rheumatoid arthritis (RA). This article highlights the controversies surrounding the definition of remission and reviews the potential of current treatment options to achieve remission. Defining "true" remission can be difficult based on current criteria, which do not consider structural and physical function. Nonetheless, considerable advances in recent years have made the concept of remission a realistic goal. In early RA, substantial and largely irreversible radiographic damage is seen in 60% of patients within the first 2 years of diagnosis. Early therapeutic intervention would ideally lead to reduction in long-term disability in RA and likelihood of inducing and maintaining remission.Long-term maintenance therapy with disease-modifying antirheumatic drugs (DMARDs) has been shown to be effective in preventing flares of disease. Stopping therapy for short periods does not necessarily lead to flares, but the effect on long-term radiographic damage and potential to achieve similar levels of disease control following reinstatement of therapy is not established. Early use of tumour necrosis factor (TNF)-antagonist therapy (e.g. infliximab) has been shown to lead to significant improvement in disease activity measures (clinical and radiologic outcomes) when compared to monotherapy or combination DMARD and corticosteroid therapies. Response was shown to be sustained in 70% of patients receiving TNF-blocking therapy 1 year after stopping treatment. This suggests the significant role of TNF-blocking therapy in enabling sustainable remission without need for long-term administrations, which has important implications for favourable health economics. At present, little published evidence exists on the effects of withdrawal of TNF-blocking therapy in patients with established RA in remission. In conclusion, evidence indicates that remission is a realistic goal, but more evidence is required to establish optimal treatment strategies and define criteria for remission that include imaging and immunological as well as clinical assessment of the disease state.
16763462 The role of megakaryocytes in skeletal homeostasis and rheumatoid arthritis. 2006 Jul PURPOSE OF REVIEW: This review provides an update on the role of megakaryocytes in skeletal homeostasis, and discusses these findings in the context of rheumatoid arthritis. RECENT FINDINGS: Thrombocytosis is a common complication of rheumatoid arthritis, and is presumably caused by an up-regulation in megakaryocytopoiesis. In general, patients with rheumatoid arthritis exhibit localized joint bone erosion with systemic bone loss, and rheumatoid arthritis patients with thrombocytosis tend to have more severe disease. Interestingly, in addition to their role in rheumatoid arthritis with thrombocytosis, it has been demonstrated recently that megakaryocytes play a dual role in regulating skeletal mass by inhibiting bone resorption while simultaneously stimulating bone formation. This seeming contradiction in the putative role of megakaryocytes in skeletal regulation and rheumatoid arthritis is the focus of this review. SUMMARY: In rheumatoid arthritis there are substantial increases in the levels of several pro-inflammatory pleiotropic cytokines. As would be expected, in addition to their role in inflammation, these cytokines play a critical role in the megakaryocytopoiesis seen in patients who develop reactive thrombocytosis, and these cytokines also are known to regulate osteoclastogenesis. Thus, it appears that in rheumatoid arthritis with reactive thrombocytosis, the ability of the cytokines to enhance osteoclastogenesis outweighs the ability of megakaryocytes to inhibit osteoclastogenesis.
17763202 The clinical role of IL-23p19 in patients with rheumatoid arthritis. 2007 Jul OBJECTIVE: To determine the clinical implications of the over-expression of synovial and circulating interleukin (IL)-23p19 and the correlation between IL-23p19 and other cytokines such as IL-17, tumour necrosis factor (TNF)alpha, and IL-1beta in rheumatoid arthritis (RA). METHODS: Synovial fluid (SF) and sera of 22 patients with RA were obtained during knee arthrocentesis and stored at -20 degrees C. Tender/swollen joint counts, 100-mm visual analogue scale (VAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and antibodies to cyclic citrullinated peptide (anti-CCP Ab) were measured. Bony erosions were determined by X-rays. Serum and SF IL-23p19, IL-17, TNFalpha, and IL-1beta concentrations were measured by sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The concentration of IL-23p19 correlated with the concentration of IL-17 in SF and sera, and with the concentrations of TNFalpha and IL-1beta in sera. SF IL-23p19 concentration was higher in patients who had bony erosions than those who had not. However, there was no correlation between IL-23p19 concentrations and other clinical parameters of RA. CONCLUSION: Upregulated IL-23p19 in SF might be involved in joint destruction in RA through interplay with other cytokines such as IL-17, TNFalpha, and IL-1beta.
17159015 C-reactive protein in the prediction of rheumatoid arthritis in women. 2006 Dec 11 BACKGROUND: The purpose of this study was to examine whether levels of C-reactive protein (CRP), a sensitive marker of disease activity in rheumatoid arthritis (RA), are associated with increased risk of subsequent RA. METHODS: Eligible subjects were 39 876 healthy women from the Women's Health Study, a completed randomized trial of aspirin and vitamin E in cardiovascular disease and cancer prevention, begun in 1992. We included 27 939 women who provided blood samples at baseline that could be assayed for CRP. RESULTS: During 9.9 years of follow-up, 398 women reported a new diagnosis of RA. Of these, 90 cases were confirmed on medical chart review using American College of Rheumatology criteria. In age-adjusted analysis, the relative risks for developing confirmed, incident RA associated with increasing tertiles of CRP (first, second, and third) were 1.00 (reference value), 0.94 (0.54-1.61), and 1.29 (0.78-2.12) (P = .30 for trend). Further adjustment for randomized treatment, age, body mass index, and smoking demonstrated corresponding relative risks of 1.00 (reference value), 0.95 (0.55-1.65), and 1.33 (0.77-2.30) (P = .48 for trend). When we examined whether CRP levels predicted incident RA within 4 years, between 5 to 8 years, and 9 or more years after CRP measurement, we found no significant associations for any time period. CONCLUSIONS: In this prospective study of healthy women, a single CRP level did not predict increased risk of RA. Furthermore, CRP measurement closer to the time of diagnosis was not predictive. The consistency of this effect throughout different time periods from diagnosis suggests that CRP does not have a large effect in predicting incident RA.
19077182 Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-C 2008 INTRODUCTION: Antibodies against cyclic citrullinated peptides (CCPs) are useful for diagnosing rheumatoid arthritis (RA). Antibodies to mutated citrullinated vimentin (MCV) were described recently in RA. The aims of this study were to evaluate the usefulness of anti-MCV for diagnosing RA in anti-CCP-negative patients and to monitor anti-MCV titres during infliximab therapy for RA. METHODS: We studied two groups of RA patients, one with (n = 80) and one without (n = 76) anti-CCP antibodies. The specificity of anti-MCV was evaluated by investigating 50 healthy controls and 158 patients with other rheumatic diseases (51 psoriatic rheumatism, 58 primary Sjögren syndrome, and 49 ankylosis spondylitis). Serum anti-MCV and anti-CCP titres were measured in 23 patients after 6, 12, 18, and 24 months of infliximab treatment. Anti-CCP2 and anti-MCV levels were assayed using a commercial enzyme-linked immunosorbent assay. IgM rheumatoid factor was determined by nephelometry. RESULTS: In accordance with the cutoff values recommended by the manufacturer, the specificity of anti-MCV antibodies was 90.9%. We adjusted the cutoff values to obtain the same specificity as that of anti-CCP antibodies (94.2%). With this optimal cutoff, anti-MCV antibodies were found in 11.8% (9/76) of RA patients without anti-CCP, and similarly, anti-CCP antibodies were found in 11.2% (9/80) of RA patients without anti-MCV. Anti-MCV antibodies were positive in 6 patients who tested negative for both anti-CCP and rheumatoid factor. Anti-MCV titres were significantly decreased after 18 and 24 months of infliximab therapy compared with baseline (P < 0.01) as a significant decrease of anti-CCP levels occurred only at 24 months (P < 0.04). Moreover, an anti-MCV decrease was significantly associated with DAS28 (disease activity score using 28 joint counts) improvements 12 months into therapy. CONCLUSIONS: Our results suggest that anti-MCV antibodies may be valuable for diagnosing RA in anti-CCP-negative patients without replacing them as an equivalent number of anti-CCP-positive RA patients test negative for anti-MCV. Moreover, anti-MCV antibodies could be useful for monitoring the effects of infliximab therapy.
16219709 Twenty-eight-joint counts invalidate the DAS28 remission definition owing to the omission 2006 May OBJECTIVE: To compare 28 joint disease activity score (DAS28) remission with comprehensive joint count DAS remission in rheumatoid arthritis. METHODS: 620 actually measured paired observations of DAS28 and DAS were analysed in 155 patients. Discordant observations (either DAS or DAS28 below remission cut off level: 1.6 for DAS and 2.6 for DAS28) and concordant observations (both DAS and DAS28 below their remission cut off level) were analysed separately. RESULTS: 91 of 620 paired DAS observations (15%) were discordant; 87 (in 53 patients) comprised observations in which the DAS28 remission criterion, but not the DAS remission criterion, was met. The reverse was found in only four observations, which were therefore omitted. With the original DAS as standard, DAS28 sensitivity was 95% and specificity 84%. Probability plots showed a swollen joint count >0 in 75% of discordant pairs v 48% of concordant pairs. The same was found for total joint count (TJC >0 in 90% v 40%; median TJC, 0 v 6) and patient global assessment, but not for ESR. Individual joint analysis showed that 51% of discordant v 18% of concordant observations (p<0.0005) had involvement of lower extremity joints that are not included in the DAS28. CONCLUSIONS: DAS remission is more conservative than DAS28 remission. Activity (tenderness and swelling) in joints not included in the reduced joint counts (ankles, feet) mainly account for the discrepancy between the two assessments. DAS28 remission at a cut off level of 2.6 has insufficient construct validity and should be used with caution in clinical practice and clinical trials.
17583780 Evaluation of pain behavior and bone destruction in two arthritic models in guinea pig and 2007 Aug The primary aim of the study was to describe and correlate pain behavior and changes in bone morphology in animal models of arthritis both in rats and guinea pigs. Either complete Freund's adjuvant (CFA) or mono-iodoacetate (MIA) solution was injected into the left knee joint to obtain a model for rheumatoid arthritis and osteoarthritis, respectively. Subsequently, animals were behaviorally tested during a period of 12 days after CFA injection and at least 19 days after MIA injection. During these observation periods increasing pain behavior was observed, characterized by decreased von Frey mechanical thresholds and weight bearing on the affected limb. In Hargreaves' paw flick test slightly increased thermal hypersensitivity was observed in some instances in guinea pigs. In rats there was also decreased limb-use during forced ambulation. To evaluate bone destruction mu-computed tomography scans of the arthritic knee were taken on the last experimental day. Different bone parameters indicative of osteolysis and decreased trabecular connectivity were significantly correlated with the observed pain behavior. Detailed description of morphological changes in arthritic joints better characterizes the different animal models and might add to the knowledge on the working mechanisms of analgesic compounds that have an influence on bone structures in arthritis.
16396977 Safety of extended treatment with anakinra in patients with rheumatoid arthritis. 2006 Aug OBJECTIVE: To determine the safety profile of anakinra after extended exposure in a diverse clinical trial population of patients with rheumatoid arthritis. METHODS: A six month, randomised, double blind phase comparing anakinra (100 mg/day) with placebo was followed by open label anakinra treatment for up to three years in patients with rheumatoid arthritis. Concomitant non-steroidal anti-inflammatory drugs, corticosteroids, and other disease modifying antirheumatic drugs were permitted. RESULTS: In all 1346 patients with rheumatoid arthritis received anakinra for up to three years. Patients had varying levels of disease severity, concomitant drug use, and comorbid conditions. Cumulative, exposure adjusted event (EAE) rates for all adverse events (AEs), serious AEs, and deaths were similar during each year of anakinra treatment; the overall rate (0 to 3 years) was similar to that observed for controls during the blinded phase. The most frequent AEs were injection site reactions (122.26 events/100 patient-years), rheumatoid arthritis progression (67.80 events/100 patient-years), and upper respiratory infections (26.09 events/100 patient-years). The EAE rate of serious infections was higher for patients treated with anakinra for 0 to 3 years (5.37 events/100 patient-years) than for controls during the blinded phase (1.65 events/100 patient-years). However, if the patient was not receiving corticosteroid treatment at baseline, the serious infection rate was substantially lower (2.87 event/100 patient-years). The overall incidence of malignancies was consistent with expected rates reported by SEER. Neutralising antibodies developed in 25 patients, but appeared to be transient in 12; neutralising antibody status did not appear related to occurrence of malignancies or serious infections. There were no clinically significant trends in laboratory data related to anakinra. CONCLUSION: Anakinra is safe and well tolerated for up to three years of continuous use in a diverse population of patients with rheumatoid arthritis.
17493519 Simulations showed that validation of database-derived diagnostic criteria based on a smal 2007 Jun OBJECTIVE: To evaluate alternative approaches to correct for bias due to inaccurate diagnostic criteria in database studies of associations. STUDY DESIGN AND SETTINGS: A simulation study of a hypothetical cohort of 10,000 subjects selected based on database-derived diagnostic criteria with positive predictive value (PPV) of either 53% or 80%. Analyses focus on the putative association between a drug and the time to a negative outcome. The association is confounded for "false positive" subjects, where the drug acts as a marker for unobserved frailty. First, we estimate the conventional multivariable Cox's Model 1. We then assume having in-depth evaluation of a fraction of subjects, which permits estimating the probabilities of having the disease for all subjects in the cohort. Alternative correction methods use the estimated probability as a confounder (Model 2), a modifier of the drug effect (Model 3), or an importance weight (Model 4). RESULTS: With a PPV of 53%, Models 1 and 2 induced about 50% underestimation bias for the drug effect. Interaction-based Model 3 yielded the least biased estimates (25% bias), whereas weighting by probability (Model 4) resulted in slightly more biased (33%), but more stable estimates. CONCLUSION: Proposed methods help reducing bias due to sample contamination.
17568789 Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast 2007 Sep Gene expression profiling of rheumatoid arthritis (RA) and osteoarthritis (OA) joint tissue samples provides a unique insight into the gene signatures involved in disease development and progression. Fibroblast-like synovial (FLS) cells were obtained from RA, OA and control trauma joint tissues (non-RA, non-OA) and RNA was analyzed by Affymetrix microarray. Thirty-four genes specific to RA and OA FLS cells were identified (P<0.05). HOXD10, HOXD11, HOXD13, CCL8 and LIM homeobox 2 were highly and exclusively expressed in RA and CLU, sarcoglycan-gamma, GPR64, POU3F3, peroxisome proliferative activated receptor-gamma and tripartite motif-containing 2 were expressed only in OA. The data also revealed expression heterogeneity for patients with the same disease. To address disease heterogeneity in RA FLS cells, we examined the effects of clinical disease parameters (Health Assessment Questionnaire (HAQ) score, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF)) and drug therapies (methotrexate/prednisone) on RA FLS cell gene expression. Eight specific and unique correlations were identified: human leukocyte antigen (HLA)-DQA2 with HAQ score; Clec12A with RF; MAB21L2, SIAT7E, HAPLN1 and BAIAP2L1 with CRP level; RGMB and OSAP with ESR. Signature RA FLS cell gene expression profiles may provide insights into disease pathogenesis and have utility in diagnosis, prognosis and drug responsiveness.
18951757 [New autoanti-bodies in rheumatoid arthritis: anti-citrullinated protein or peptide autoan 2008 Dec New treatment strategies require that rheumatoid arthritis (RA) be diagnosed as early as possible. New diagnostic markers were required, because rheumatoid factors (RF), until now criteria for classification of RA, are not sufficiently specific and sometimes appear late, thereby limiting their diagnostic usefulness. The objective of this review is to describe the current state of knowledge and more particularly to analyze the interest of new RA autoanti-bodies, called anti-peptide or anti-citrullinated protein anti-bodies (ACPA). Other autoanti-bodies have been described, including anti-Sa, anti-alpha enolase, and anti-calpastatin autoanti-bodies. Nonetheless, their diagnostic value remains limited compared to ACPA. Accordingly, in daily practice today, the only autoanti-bodies that must be tested for to diagnose RA are the ACPAs and RFs. The discovery of ACPA (initially called anti-keratin and anti-perinuclear anti-bodies) was a major step forward for the laboratory diagnosis of RA. The tests most often used routinely areenzyme-linked immunosorbent assays(ELISA) with cyclic citrullinated peptides, whence the name anti-CCP autoanti-bodies. Accordingly, the two terms ACPA and anti-CCP can both be used. The diagnostic value, in particular their specificity, is on the order of 95%, regardless of the method of identification. These markers are very useful and are often present earlier than RF. These ACPA also have prognostic value because they are associated with more aggressive forms of RA. On the other hand, their value over time, in particular, their fluctuation as a function of treatment, is more controversial. In practice, it is recommended to test for both RF and ACPA in a diagnostic work-up for early RA. During follow-up, the value of testing for these autoanti-bodies has not been demonstrated, but additional studies are still necessary with the anti-CCP autoanti-bodies and the new anti-citrullinated protein autoanti-bodies.
17970184 Sagittal alignment of the subaxial cervical spine after C1-C2 transarticular screw fixatio 2007 Aug Several articles reported the association between the development of subaxial kyphosis and the hyperlordotic fixation of C1-C2. However, their patients were heterogeneous in both primary disease and operative procedure. Transarticular screw fixation has become a popular procedure for C1-C2 arthrodesis instead of wiring techniques in which C1-C2 is difficult to fix in the intended alignment. Furthermore, in rheumatoid arthritis (RA) patients, subaxial lesions play an important role in potential subaxial alignment changes. The subaxial influences after C1-C2 transarticular screw fixation in patients with RA are unclear. To investigate the radiographic features of the subaxial cervical spine after C1-C2 transarticular screw fixation for RA, we reviewed 28 cases of C1-C2 transarticular screw fixation for rheumatoid atlanto-axial subluxation. The sagittal alignment of C1-C2 and the subaxial cervical spine was measured and the factors that affect subaxial alignment were investigated. Subaxial alignment became less lordotic in the postoperative course. The C1-C2 fixation angle and subaxial alignment showed a negative linear correlation. However, no significant correlation was found between changes in the C1-C2 angle and changes in the subaxial alignment. Four patients had a postoperative kyphotic subaxial deformity. Neurologic deterioration recurred in 4 patients, because of the postoperative development of subaxial subluxation. Common radiographic changes included an increase in C1-C2 lordosis, constant inclination of C1, an anterior shift of C2, and a decrease in C2-C7 lordosis. Many factors, not only C1-C2 angle, are associated with subaxial sagittal alignment change after C1-C2 transarticular screw fixation.
16785830 Expectations from patients with rheumatoid arthritis regarding COX-2s: cutting to the hear 2006 Before the withdrawal of 2 COX-2 selective agents (COX-2s) from the market, many rheumatoid arthritis patients were using these products regularly, with disease-modifying antirheumatic agents. Clinical trials have shown benefit of COX-2s equivalent to nonselective nonsteroidal anti-inflammatory drugs (NS-NSAIDs) in rheumatoid arthritis. Better gastrointestinal (GI) safety has been demonstrated with COX-2s; numerical but not statistical benefit with concomitant use of cardiovascular (CV) doses of aspirin. COX-2 benefit may extend to lower GI blood loss against which proton pump inhibitors are not protective. COX-2s are associated with hypertension and edema of similar magnitude to NS-NSAIDs in predisposed individuals. Epidemiologic studies and clinical trials have confirmed the association of serious thromboembolic (CV) events and congestive heart failure with rofecoxib>25 mg daily, celecoxib, and NS-NSAIDs, although there is a paucity of long-term data. Important questions remain regarding relative GI and CV risks: is concomitant aspirin protective when coadministered with COX-2s? Does this abrogate their GI benefit? As identified many years ago with NS-NSAIDs, patients may respond to one and not another; COX-2s should be considered individually and not as a single "class." Patients deserve the opportunity to make a choice about the perceived benefit/risk assessment when using these therapies, with the collaboration of their physician.