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ID PMID Title PublicationDate abstract
22174197 Performance of risk indices for identifying low bone mineral density and osteoporosis in M 2012 Feb OBJECTIVE: We evaluated the utility of 6 generic and 2 specific risk indices for identifying low bone mineral density (BMD) or osteoporosis in women with rheumatoid arthritis (RA); and their correlation with 10-year probability of fractures as assessed with the World Health Organization fracture risk assessment (FRAX) tool. METHODS: Mexican Mestizo women with RA were evaluated in this cross-sectional study using 6 generic indices [Simple Calculated Osteoporosis Risk Estimation (SCORE); Osteoporosis Risk Assessment Instrument (ORAI); Osteoporosis Self-Assessment Tool; Age, Body Size, No Estrogen; Osteoporosis Index of Risk (OSIRIS); and Guidelines of the US National Osteoporosis Foundation], 2 specific indices (Amsterdam and modified Amsterdam), and FRAX. BMD results on dual-energy x-ray absorptiometry (DEXA) at the lumbar spine and femoral neck were considered the "gold standard." Sensitivity, specificity, and predictive values (PV) of the indices and their correlations with FRAX results were estimated. RESULTS: Among 191 patients, 46 had osteoporosis (24.1%) and 119 had low BMD (62.3%). For predicting osteoporosis, SCORE showed the highest sensitivity (96%), whereas OSIRIS (87%) and ORAI (82%) showed the highest specificities. OSIRIS also had the greatest positive PV (92%). The specific indices had low sensitivity and low specificity (Amsterdam, 50% and 79%, respectively; modified Amsterdam, 56% and 70%). All the indices had a low but significant correlation with FRAX. CONCLUSION: These findings support the use of some generic indices to identify patients with RA who should undergo DEXA testing. Currently available specific indices did not perform satisfactorily. New specific risk indices for osteoporosis in RA should be developed to increase sensitivity and specificity for predicting osteoporosis.
23073309 Treat-to-target: measures. 2012 Jul Current approach to rheumatoid arthritis (RA) treatment combines early and aggressive therapy, with methotrexate as the anchor medication and monitoring disease activity to achieve the best possible outcome for patients. To recognise which patients are responding treatment and reaching low disease activity levels or remission, an objective outcome measure needs to be utilised in routine clinical care. DAS28, SDAI, CDAI and RAPID3 are all validated and similarly functioning measures that can be of use in everyday care, allowing rheumatologists to treat-to-target. The main challenge remains getting all rheumatologists to start using one of these measures as part of the care they provide.
21898074 Effectiveness and safety of adalimumab in Japanese patients with rheumatoid arthritis: ret 2012 Jun We retrospectively investigated the ability of adalimumab (ADA) to reduce disease activity, improve physical function, and retard the progression of structural damage in 167 patients with rheumatoid arthritis. Clinical and functional outcomes were compared between patients with or without prior biologic treatment and those with or without concomitant methotrexate (MTX) treatment. At week 52, 38.3% achieved clinical remission: 42.4 and 28.6% of patients achieved remission in those without and with previous biologics, respectively, while 42.7 and 12.5% of patients achieved remission in those with and without concomitant MTX, respectively. ADA treatment significantly reduced the rate of radiographic progression from 27.1 ± 46.0 (median 13.6; 25th-75th percentiles 8.3 to 28.9) at baseline to 0.8 ± 5.0 (median 0.0; 25th-75th percentiles -0.9 to 2.0) at week 52 (P < 0.0001). Radiographic progression was absent in 59.8% of patients. Sixty adverse events (34.21/100 patient-years) were reported, 16 of which were serious (9.12/100 patient-years). ADA therapy is highly effective for reducing disease activity, improving physical function, and limiting radiographic progression. It is generally safe and well tolerated by Japanese RA patients in routine clinical practice.
21297330 Minimal-change nephrotic syndrome associated with isoniazid in anti-tuberculosis chemoprop 2011 A 66-year-old woman with seropositive rheumatoid arthritis (RA) and latent tuberculosis infection developed minimal-change nephrotic syndrome following the initiation of anti-tuberculosis chemoprophylaxis with isoniazid. This is the first reported case of an isoniazid-induced nephrotic syndrome. Isoniazid as a single-drug intervention is widely accepted as a safe and effective means of anti-tuberculosis chemoprophylaxis, particularly for RA patients with latent tuberculosis infection; the present case, however, demonstrates that isoniazid has the potential to induce minimal-change nephrotic syndrome, even when used as a single-drug intervention.
20563870 The PADI4 gene does not contribute to genetic susceptibility to rheumatoid arthritis in Ch 2011 Dec The Peptidyl arginine deiminase, type IV (PADI4) gene has been suggested to have an association with rheumatoid arthritis (RA) in several populations. But its role in Chinese RA is not clarified. We investigated five single-nucleotide polymorphisms (SNPs) of PADI4 as PADI4-89 (rs11203366), PADI4-90 (rs11203367), PADI4-92 (rs874881) PADI4-94 (rs2240340), and PADI4-104 (rs1748033) in Chinese Han population. A total of 378 unrelated RA patients and 204 healthy controls were genotyped for the five SNPs. Individual allele, genotype and haplotype frequencies were compared between patients and controls. No significant differences in the frequency of PADI4 alleles, genotypes and haplotypes were observed between the patients and controls except PADI4-92. These data indicated that PADI4 polymorphisms were unlikely to play an important role in the susceptibility to RA in Chinese Han population.
22332155 Lack of head-to-head trials and fair control arms: randomized controlled trials of biologi 2012 Feb 13 BACKGROUND: One of the key elements of comparative treatment effectiveness research is head-to-head trials. We herein describe the control arms and the treatment received by patients in recently conducted or ongoing randomized controlled trials of biologic disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis. METHODS: We identified all protocols recorded in ClinicalTrials.gov to October 1, 2009. We extracted trial length and funding, prior treatment, disease activity in eligible patients, and the treatment received in both trial arms. RESULTS: Among the 91 trials identified (15 DMARD-naive trials, 63 biologic-naive trials, and 13 biologic-second-line trials) involving 18, 554 patients in control arms (3059, 13 095, and 2400 patients, respectively), only 5 compared biologic DMARDs head-to-head (2 of 7 noncommercially funded trials and 3 of 84 commercially funded trials). Two-thirds (66%) of these trials are ongoing. Networks of treatment comparisons reflect a predominant use of placebo as a comparator (81 of 102 comparisons among the 91 trials). In all 15 DMARD-naive trials, all control patients received a new treatment. In 54 of the 63 biologic-naive trials, 9224 of the 13, 095 control patients received their previously ineffective treatment, 3848 for more than 6 months, despite high levels of disease activity and contrary to guidelines. In biologic-second-line trials, 851 of the 2400 control patients received treatment comparable to their previously ineffective one. CONCLUSIONS: Head-to-head trials of biologic DMARDs are still exceptions. Exposing patients in control arms who had a previous partial response or nonresponse to an inadequate treatment could lead to irreversible deterioration in condition.
21557995 Extract of the dried heartwood of Caesalpinia sappan L. attenuates collagen-induced arthri 2011 Jun 14 AIM OF THIS STUDY: To confirm the anti-arthritic effect and explore the potential mechanism of the dried heartwood of Caesalpinia sappan L. (HCS) on collagen-induced arthritis (CIA) in rats, an animal model of rheumatoid arthritis. MATERIALS AND METHODS: CIA was induced in male Wistar rats by intradermal injection of bovine collagen-II in Freund's incomplete adjuvant (IFA). The rats in the onset of arthritis were treated daily with oral administration of an ethanol extract from HCS (EHCS) at different doses (1.2, 2.4 and 3.6g/kg) or olive oil-vehicle for 10 days. Paw swelling, arthritis index, radiographic and histopathologic changes were evaluated to confirm the anti-arthritic effect of EHCS on CIA in rats. Levels of proinflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) as well as prostaglandin E2 (PGE2) in blood and expression of cyclooxygenase-2 (COX-2) and transcription factor NF-κB p65 in paw cartilage were detected to further study the molecular mechanism of the anti-arthritic effects of EHCS on CIA in rats. In addition, the adverse effects of EHCS on liver and kidney of rats were also evaluated. RESULTS: The results showed that the EHCS markedly attenuated collagen-induced arthritis and reduced the levels of IL-1β, IL-6, TNF-α and PGE2 in serum and the expression of COX-2 and transcription factor NF-κB p65 in paw cartilage of CIA rats. EHCS (3.6g/kg) induced slight hepatotoxicity and body weight loss. CONCLUSION: These results indicate that EHCS significantly attenuates CIA in rats by decreasing the levels of IL-1β, IL-6, TNF-α and PGE2 in serum and the expression of COX-2 and transcription factor NF-κB in paw cartilage.
20012964 The diagnostic utilities of anti-agalactosyl IgG antibodies, anti-cyclic citrullinated pep 2011 Mar The purpose of this study was to investigate the diagnostic utilities of anti-agalactosyl IgG antibody (CARF), anti-cyclic citrullinated peptide (CCP) antibody and rheumatoid factor (RF) in rheumatoid arthritis (RA), non-RA rheumatic diseases, and chronic viral hepatitis. The authors determined serum levels of CARF and anti-CCP2 by ELISA and IgM-RF by a immunonephelometric method in 834 controls and in 397 patients with the following conditions: RA (100), non-RA rheumatic diseases [systemic lupus erythematosus (SLE) 30, primary Sjogren's syndrome 18, systemic sclerosis 30, inflammatory myositis 19], chronic viral hepatitis B and C (HBV 100, HCV 100). The sensitivities of CARF (83%) and anti-CCP (85%) were significantly higher than that of RF (75%, p = 0.01, respectively) in RA, and the specificity of anti-CCP (98%) was significantly higher than those of CARF (92%) and RF (90%, p < 0.001, respectively). A comparison of receiver operating characteristic (ROC) curves revealed that the diagnostic accuracies of CARF and anti-CCP were superior to that of RF (CARF vs. RF, p = 0.008, anti-CCP vs. RF, p = 0.017) in RA. CARF positivity was significantly higher than those of anti-CCP (p = 0.007) and RF (p = 0.008) in systemic sclerosis, and the positivity of CARF was significantly higher than that of anti-CCP in Sjogren's syndrome (p = 0.016). Furthermore, CARF had significantly higher positivity than anti-CCP or RF in chronic viral hepatitis B and C. Finally, the titers of these three markers in RA were significantly higher than in non-RA rheumatic diseases and in chronic viral hepatitis B and C. Our results suggest that anti-CCP is the most useful serologic marker for the differentiation of RA and non-RA rheumatic diseases, and chronic viral hepatitis B and C.
22127691 Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced 2011 Dec OBJECTIVE: Rituximab significantly improves the signs and symptoms of rheumatoid arthritis (RA) and slows the progression of joint damage. The aim of this study was to identify clinical characteristics and biomarkers that identify patients with RA in whom the clinical benefit of rituximab may be enhanced. METHODS: The study group comprised 1,008 RA patients from 2 independent randomized placebo-controlled phase III clinical trials (REFLEX [Randomized Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis] and SERENE [Study Evaluating Rituximab's Efficacy in Methotrexate Inadequate Responders]). A novel threshold selection method was used to identify baseline candidate biomarkers present in at least 20% of patients that enriched for placebo-corrected American College of Rheumatology 50% improvement (ACR50 response; a high clinical efficacy bar) at week 24 after the first course of rituximab. RESULTS: The presence of IgM rheumatoid factor (IgM-RF), IgG-RF, IgA-RF, and IgG anti-cyclic citrullinated peptide (anti-CCP) antibodies together with an elevated C-reactive protein (CRP) level were associated with enhanced placebo-corrected ACR50 response rates in the REFLEX patients with RA who had an inadequate response to anti-tumor necrosis factor therapies. These findings were independently replicated using samples from patients in SERENE who had an inadequate response to disease-modifying antirheumatic drug treatment. The combination of an elevated baseline CRP level together with an elevated level of any RF isotype and/or IgG anti-CCP antibodies was further associated with an enhanced benefit to rituximab. CONCLUSION: The presence of any RF isotype and/or IgG anti-CCP autoantibodies together with an elevated CRP level identifies a subgroup of patients with RA in whom the benefit of rituximab treatment may be enhanced. Although the clinical benefit of rituximab was greater in the biomarker-positive population compared with the biomarker-negative population, the clinical benefit of rituximab compared with placebo was also clinically meaningful in the biomarker-negative population.
22143988 The pattern-recognition receptor nucleotide-binding oligomerization domain--containing pro 2012 May OBJECTIVE: Pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-containing protein 2 (NOD-2), have been shown to contribute to the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to analyze the expression, regulation, and function of the PRR NOD-1 in RA synovial fibroblasts (RASFs), and to examine its interaction with other PRRs. METHODS: Expression of NOD-1 was analyzed by immunohistochemistry in synovial tissue from RA patients, psoriatic arthritis patients, gout patients, and osteoarthritis (OA) patients. RASFs and human monocyte-derived macrophages (HMDMs) were stimulated with L-alanyl-γ-D-glutamyl-meso-diaminopimelic acid, palmitoyl-3-cysteine-serine-lysine-4, poly(I-C), lipopolysaccharide, heat-inactivated bacteria, tumor necrosis factor α (TNFα), or interleukin-1β (IL-1β). Expression levels of IL-6, CCL5, matrix metalloproteinases (MMPs), NODs, and TLRs were measured by real-time reverse transcription-polymerase chain reaction and/or enzyme-linked immunosorbent assay. NOD-1 and NOD-2 were silenced with target-specific small interfering RNA. Phosphorylation of IL-1 receptor-associated kinase 1 (IRAK-1) was measured by Western blotting. RESULTS: Expression of NOD-1 protein was significantly increased in RA synovium compared to OA synovium. The basal expression of NOD-1 was similar in RASFs, OASFs, healthy control peripheral blood mononuclear cells, and healthy control HMDMs. Stimulation of RASFs with TLR-3 up-regulated the expression of NOD-1. Expression of IL-6, CCL5, MMPs, TLR-2, and NOD-2 was significantly up-regulated in RASFs by stimulation with the NOD-1 ligand. A synergistic effect on IL-6 production was observed in cells stimulated with NOD-1 and TLR-2 ligands or NOD-1 and TLR-4 ligands. Silencing of NOD-1, but not NOD-2, decreased the levels of IL-6 in RASFs after stimulation with TLR-2 and IL-1β, and blocked the phosphorylation of IRAK-1. CONCLUSION: NOD-1 is strongly expressed in different cell types in the synovial tissue of patients with RA. These results indicate that NOD-1, either alone or interacting with other inflammatory mediators, can play an important role in the chronic and destructive inflammation of the joints in RA.
22125252 A new high-flexion knee scoring system to eliminate the ceiling effect. 2012 Feb BACKGROUND: Various scoring systems document improvement after TKA, but most are associated with a ceiling effect that may fail to distinguish between patients having different levels of knee function after TKA. We therefore developed a new scoring system for patients with higher levels of flexion to eliminate ceiling effects observed with current systems. QUESTIONS/PURPOSES: The purposes of this study were (1) to determine whether the high-flexion knee score eliminates the ceiling effect, (2) to assess the validity and responsiveness of the high-flexion knee score, and (3) to determine whether the high-flexion knee score can aid in differentiation of the knee status of patients at the ceiling level. METHODS: We prospectively studied 165 patients with 201 well-functioning knees who had undergone primary TKA. We obtained Knee Society scores, WOMAC scores, Feller scores, SF-36 scores, and high-flexion knee scores for all patients. The high-flexion knee score includes items that reflect knee function in the high functional range, such as sitting on or rising from the floor, squatting, or kneeling. We determined the ceiling effects and score distributions of various scoring systems. We performed a convergent validity test of the high-flexion knee score by correlation analysis with these various scoring systems. Responsiveness of the high-flexion knee score was assessed by correlation analysis of changes in various scoring systems. To determine whether the high-flexion knee score can aid in differentiation of knee status of patients at the ceiling level, relative responsiveness of the various scores in the ceiling versus below the ceiling range was determined. RESULTS: The high-flexion knee score showed no ceiling effect, whereas the other systems did. Addition of the high-flexion knee score to the other scoring systems eliminated these ceiling effects and resulted in more normalized score distributions. The high-flexion knee score correlated (r = -0.77) with WOMAC in postoperative scores, and it also correlated with the changes in WOMAC (r = -0.69) and SF-36 physical functioning (r = 0.62). The correlation of WOMAC score with SF-36 physical function score was lower in patients at the ceiling level of the Knee Society knee score and Knee Society function score, compared with the correlation at below-ceiling range, whereas the high-flexion knee score maintained a correlation with the SF-36 physical function score, even at the ceiling level of the Knee Society knee score and Knee Society function score. CONCLUSIONS: Compared with other systems, the high-function knee score appears valid for evaluating the knee status in the high-flexion range. Our data suggest the high-flexion knee score differentiates among the knee status in the high-function range. Furthermore, the high-function knee score eliminates the ceiling effect of the currently used scoring tools, and thus may be useful when combined with other scoring systems. LEVEL OF EVIDENCE: Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.
21885199 Is rheumatoid arthritis a risk factor for oral bisphosphonate-induced osteonecrosis of the 2011 Nov Bisphosphonate-related osteonecrosis of the jaws is a relevant side-effect of these drugs that has been generating a great concern through increasing reports, worldwide, of this bone necrosis. Among several BRONJ hypothetical co-factors that could play a role in BRONJ pathogenesis, rheumatoid arthritis (RA) has been included as a relevant risk factor for BRONJ; however, until now the relationship between these diseases has not been fully explained. Thus, the purpose of this paper is to establish hypothetical factors that could link these two diseases, considering mainly inflammatory components and the organism effects of medicines used to treat RA, particularly steroids and methotrexate (MTX).
21536244 [Connective tissue diseases and psoriasis]. 2011 Sep Psoriasis is an autoimmune chronic inflammatory skin disease that is common in Spain. Connective tissue diseases are a heterogeneous group of conditions characterized by the abnormal function or structure of one or more of the elements that make up connective tissue. These diseases are also autoimmune in origin. In spite of the high prevalence of psoriasis in the general population, its association with a connective tissue disease such as systemic lupus erythematosus, dermatomyositis, scleroderma, or rheumatoid arthritis has only occasionally been reported. It is nevertheless important to have an understanding of such associations, given their significant clinical and therapeutic implications. The association between psoriasis and systemic lupus erythematosus is the one most often described, although the few reports available in the literature have mostly involved single cases. This review will also look at the characteristics of patients with psoriasis and dermatomyositis, mainly focusing on clinical features. The associations between psoriasis and either rheumatoid arthritis or systemic sclerosis will be examined more briefly. The review therefore aims to reflect the literature on psoriasis in association with rheumatic diseases, including coverage of etiologic, pathogenic, clinical, and therapeutic aspects. We emphasize that such cases should be managed by a multidisciplinary team in which care will usually be shared by a rheumatologist and a dermatologist.
23192908 Positive synovial vascularity in patients with low disease activity indicates smouldering 2013 Mar OBJECTIVE: To investigate the relationship between synovial vascularity and joint damage progression in each finger joint of patients with RA under low disease activity during treatment with biologic agents. METHODS: We studied 310 MCP and 310 PIP joints of 31 patients with active RA who were administered adalimumab (ADA) or tocilizumab (TCZ). Patients were examined with clinical and laboratory assessments. Power Doppler sonography was performed at baseline and at weeks 8, 20 and 40. Synovial vascularity was evaluated according to quantitative measurement. Hand and foot radiography was performed at baseline and at week 50. RESULTS: Composite scores of the DAS with 28 joints and the Simplified Disease Activity Index (SDAI) were significantly decreased from baseline to week 8, being sustained at a low level by biologic agents during the observational period. MCP and PIP joints with positive synovial vascularity after week 8 showed more subsequent joint damage progression than joints without synovial vascularity throughout the follow-up. The changes in radiographic progression in these joints were independent of the sum of synovial vascularity from baseline to week 40 or the occasional occurrence of positive synovial vascularity. CONCLUSION: Smouldering inflammation reflected by positive synovial vascularity under low disease activity was linked to joint damage. The damage progressed irrespective of the severity of positive synovial vascularity. Even with a favourable overall therapeutic response, monitoring of synovial vascularity has the potential to provide useful joint information to tailor treatment strategies. Trial registration. University Hospital Medical Information Network Clinical Trials Registry; http://www.umin.ac.jp/ctr/; UMIN000004476.
21485024 RAPID3 (Routine Assessment of Patient Index Data 3) severity categories and response crite 2011 Aug OBJECTIVE: To compare categories for activity/severity according to the Disease Activity Score 28-joint count (DAS28), the Clinical Disease Activity Index (CDAI), and the Routine Assessment of Patient Index Data 3 (RAPID3), an index without formal joint counts calculated in 5 versus >100 seconds, as well as the European League Against Rheumatism (EULAR)- DAS28 and the RAPID3 response criteria, in the Rheumatoid Arthritis Prevention of Structural Damage (RAPID 1) clinical trial of certolizumab pegol (CZP). METHODS: Post hoc analyses were performed using correlations, cross-tabulations, and kappa statistics. Patients (treated with CZP plus methotrexate [MTX] or placebo plus MTX) were classified at baseline and at 52 weeks as high, moderate, low activity/severity or remission, according to the DAS28 (>5.1, >3.2 to ≤5.1, 2.6 to ≤3.2, <2.6 [total range 0-10]), the CDAI (>22, >10 to ≤22, >2.8 to ≤10, ≤2.8 [total range 0-76]), and RAPID3 (>12, >6 to ≤12, >3 to ≤6, ≤3 [total range 0-30]), as well as for good, moderate, and poor EULAR-DAS28 and proposed RAPID3 response criteria. RESULTS: All measures were correlated significantly: RAPID3 with DAS28 and CDAI (rho > 0.7), higher than erythrocyte sedimentation rate with C-reactive protein level (rho = 0.47). At 52 weeks, DAS28, CDAI, and RAPID3 low activity/remission was seen in 30%, 44%, and 42% of CZP-treated patients versus 3%, 7%, and 10% of control patients. Good, moderate, and poor EULAR-DAS28 responses were seen in 30%, 51%, and 19% of CZP-treated patients versus 3%, 28%, and 70% of control patients, and for RAPID3 in 39%, 30%, and 32% of CZP-treated patients versus 8%, 16%, and 76% of control patients. Kappa and weighted kappa values ranged from 0.36-0.53, indicating fair to moderate agreement. CONCLUSION: RAPID3, DAS28, and CDAI give similar results to distinguish CZP patients from controls in the RAPID 1 clinical trial. DAS28 is specific for clinical trials; RAPID3 appears pragmatically useful for usual care.
22083611 Effect of methotrexate on inflammatory cells redistribution in experimental adjuvant arthr 2012 Nov The aim of this study was to evaluate the morphological changes in the spleen, the thymus and the knee joints of rats with experimental adjuvant arthritis induced by Mycobacterium butyricum in the incomplete Freund's adjuvant and the effect of treatment with methotrexate (MTX). Particular attention was aimed on the redistribution of granulocytes in the tissues during the inflammatory process. Clinical parameters, e.g., joint edema, body weight and of gamma glutamyl transferase (GGT) activity as an inflammatory marker, have also been determined. Induction of adjuvant arthritis caused a significant decrease in granulocyte number in the spleen and vice versa a significant increase in the knee joints, but without significant changes in the thymus. Treatment with methotrexate reversed this phenomenon by increasing the granulocyte number in the spleen and decreasing it in knee joints. MTX decreased the joint edema as well as the activity of GGT in the spleen, modified the size of the white pulp of the spleen and increased the cortex/medulla ratio in the thymus. The observed changes support the anti-inflammatory and immunomodulatory properties of MTX supporting its use as the first-line medication in patients with rheumatoid arthritis.
22944128 [Association between the synovial expression of cyclic citrullinated peptide and susceptib 2012 Jun 19 OBJECTIVE: To analyze the association between the synovial expression of cyclic citrullinated peptide (CCP) and susceptibility variants of HLA-DRB1 shared epitope (SE) alleles and/or peptidylarginine deiminase 4 (PADI4) gene single nucleotide polymorphisms (SNP) in patients with rheumatoid arthritis (RA). METHODS: From October 2008 to December 2011, 53 RA patients and 42 controls were enrolled. The expression of CCP in RA synovial tissues was detected by immunohistochemical assay with 6×His tagged anti-CCP single chain fragment V (ScFv) antibodies generated by pHEN2 phagemid recombinant antibodies display system. PADI4 SNP was genotyped by reverse transcription cDNA sequencing and heterozygote was DNA haplotype was mapped by TA clone sequencing. HLA-DRB1 SE alleles were analyzed by sequence specific primer-polymerase chain reaction (SSP-PCR). RESULTS: The prevalence of synovial CCP expression was significantly different between RA group and the control (76.9% and 11.4% respectively, P < 0.01). The frequencies of 2 SNPs (PADI4_89 G+ and PADI4_104 T+) varied significantly between the groups(P < 0.05). Compared with the major haplotypes, only these two minor alleles were associated with the increased RA susceptibility (OR = 3.67 and 2.53, P < 0.05). SE+ alleles was strongly associated with RA susceptibility (OR = 5.57, P < 0.01). The synovial expression of CCP in RA was strongly associated with SE+ alleles, only 2 minor SNPs (PADI4_89 G+ and PADI4_104T+) and the combination. Serum anti-CCP titers were significantly associated with SE+ alleles, PADI4_104T+, SE+/PADI4_89 G+ and SE+/PADI4_104T+ haplotype. CONCLUSION: The synovial expression of CCP and the generation of anti-CCP antibodies are strongly associated with SE alleles and/or certain PADI4 gene SNP in RA.
21253738 Lack of association between promoter polymorphisms of HLA-G gene and rheumatoid arthritis 2012 Feb The aim of this study was to determine whether the HLA-G gene was associated with susceptibility to rheumatoid arthritis (RA). Major histocompatibility complex, class I, G (HLA-G) is involved in immunoregulatory processes and particularly in pathogenesis of inflammatory disorders. To investigate possible association between HLA-G and RA, 296 RA patients and 468 healthy controls were enrolled in this study. Two-promoter single-nucleotide polymorphisms (SNPs) (rs1736936, -1202T/C and rs2735022, -586C/T) in HLA-G gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). For analysis of data, Helixtree software, SNPAnalyzer, SNPStats, and Haploview version 4.2 were used. Multiple logistic regression models (codominant, dominant, and recessive) were performed for odds ratio (OR), 95% confidence interval (CI), and P value. There were no significant differences in distributions of genotypes and haplotypes between RA patients and control subjects. In clinical features of RA, we found differences between C-reactive protein levels (≥0.5 or <0.5 mg/dL) and two-promoter SNPs. Rs1736936 was significant in codominant (P = 0.028, OR = 0.66, 95% CI = 0.45-0.96) and dominant (P = 0.046, OR = 0.58, 95% CI = 0.34-0.99) models. Also, rs2735022 was significant in codominant (P = 0.038, OR = 0.67, 95% CI = 0.46-0.98) and dominant (P = 0.03, OR = 0.55, 95% CI = 0.33-0.94) models. However, these significant associations disappear after Bonferroni correction. Our results suggest that HLA-G promoter polymorphisms may be not associated with the development of RA in Korean population.
21406459 Differential diagnosis between rheumatoid arthritis and psoriatic arthritis: the value of 2011 Jun OBJECTIVE: To investigate the potential of ultrasound (US) in the differential diagnosis between rheumatoid arthritis (RA) and psoriatic arthritis (PsA) at metacarpophalangeal (MCP) joints level. METHODS: 18 RA patients and 20 PsA patients with clinical involvement of MCP joints were included. All US examinations were performed by two rheumatologists investigating: presence of joint cavity widening (JCW), synovial fluid and/or synovial hypertrophy, peritenon extensor tendon inflammation (PTI) and intra-articular or peri-tendinous power Doppler (PD) signal. RESULTS: A total of 83 MCP joints in 18 RA patients were assessed. In all of these the authors found different degrees of JCW. 15 of 83 (18%) MCP joints showed synovial fluid, whereas 68 of 83 (82%) MCP joints showed synovial hypertrophy. In 72 of 83 (86.7%) MCP joints intra-articular PD was detected. No PTI pattern was found in these patients. In PsA patients, a total of 82 MCP joints in 20 patients were assessed. 54 of 82 (65.8%) MCP joints showed PTI pattern (p = 0.001). In 50 of these 54 (92.5%) MCP joints extra-articular PD signal was detected (p = 0.001). 28 of 82 (34.1%) MCP joints showed different degrees of JCW. 6 of 28 (21.4%) MCP joints presented synovial fluid, whereas 22 of 28 (78.5%) MCP joints showed synovial hypertrophy. In 8 of 82 (9.7%) MCP joints the JCW and PTI patterns were found contemporaneously. CONCLUSIONS: Preliminary results demonstrate that PTI pattern is a higher characteristic of PsA, which suggests a potential role of US in the differential diagnosis between RA and PsA at MCP joints level.
22707613 Canadian Rheumatology Association recommendations for the pharmacological management of rh 2012 Aug OBJECTIVE: The Canadian Rheumatology Association (CRA) has developed recommendations for the pharmacological management of rheumatoid arthritis (RA) with traditional and biologic disease-modifying antirheumatic drugs (DMARD) in 2 parts. Part II, focusing on specific safety aspects of treatment with traditional and biologic DMARD in patients with RA, is reported here. METHODS: Key questions were identified a priori based on results of a national needs-assessment survey. A systematic review of all clinical practice guidelines and consensus statements regarding treatment with traditional and biologic DMARD in patients with RA published between January 2000 and June 2010 was performed in Medline, Embase, and CINAHL databases, and was supplemented with a "grey literature" search including relevant public health guidelines. Systematic reviews of postmarketing surveillance and RA registry studies were performed to update included guideline literature reviews as appropriate. Guideline quality was independently assessed by 2 reviewers. Guideline characteristics, recommendations, and supporting evidence from observational studies and randomized trials were synthesized into evidence tables. The working group voted on recommendations using a modified Delphi technique. RESULTS: Thirteen recommendations addressing perioperative care, screening for latent tuberculosis infection prior to the initiation of biologic DMARD, optimal vaccination practices, and treatment of RA patients with active or a history of malignancy were developed for rheumatologists, other primary prescribers of RA drug therapies, and RA patients. CONCLUSION: These recommendations were developed based on a synthesis of international RA and public health guidelines, supporting evidence, and expert consensus in the context of the Canadian health system. They are intended to help promote best practices and improve healthcare delivery for persons with RA.