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ID PMID Title PublicationDate abstract
21780652 [Cardiovascular risk factors in psoriatic and rheumatoid arthritis]. 2011 AIM: To study the role of conventional and new factors of cardiovascular risk in development of atherosclerosis in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PA). MATERIAL AND METHODS: Sixty patients with psoriatic arthritis, 414 RA patients and 79 healthy controls entered the trial. All of them had no manifestations of cardiovascular diseases. Screening was made of the leading risk factors of cardiovascular diseases and cardiovascular complications, thickness of the complex intima-media (TIM) of the carotid arteries, vascular wall stiffness were measured, vasoregulatory function of the endothelium, markers of endothelial damage were examined. RESULTS: Patients with psoriatic and rheumatoid arthritis were found to have increased TIM of the carotid arteries, high incidence of atherosclerotic plaques, increased stiffness, damage of the vascular wall, affected endothelial vasoregulation. These alterations were associated with high arthritis activity, systemic manifestations, seropositivity by rheumatoid factor (in RA), presence of entesitis, uveitis and dactilitis (in psoriatic arthritis), dislipidemia, arterial hypertension (AH). CONCLUSION: To determine cardiovascular risk in patients with arthritis, it is necessary to consider not only standard risk factors (dislipidemia and AH), but also severity of systemic inflammation, arterial stiffness, endothelial damage and ability of the vascular wall to relax reflecting endothelial dysfunction.
21567381 Resolution of neutrophilic inflammation by H2O2 in antigen-induced arthritis. 2011 Sep OBJECTIVE: Neutrophil accumulation contributes to the pathogenesis of rheumatoid arthritis. This study was undertaken to examine the ability of H2O2 to influence neutrophilic inflammation in a model of antigen-induced arthritis (AIA) in mice. METHODS: AIA was induced by administration of antigen into the knee joints of previously immunized mice. Neutrophil accumulation was measured by counting neutrophils in the synovial cavity and assaying myeloperoxidase activity in the tissue surrounding the mouse knee joint. Apoptosis was determined by morphologic and molecular techniques. The role of H2O2 was studied using mice that do not produce reactive oxygen species (gp91phox-/- mice) and drugs that enhance the generation or enhance the degradation of H2O2. RESULTS: Antigen challenge of immunized mice induced neutrophil accumulation that peaked at 12-24 hours after challenge. H2O2 production peaked at 24 hours, after which time, the inflammation resolved. Neutrophil recruitment was similar in wild-type and gp91phox-/- mice, but there was delayed resolution in gp91phox-/- mice or after administration of catalase. In contrast, administration of H2O2 or superoxide dismutase (SOD) resolved neutrophilic inflammation. The resolution of inflammation induced by SOD or H2O2 was accompanied by an increase in the number of apoptotic neutrophils. Apoptosis was associated with an increase in Bax and caspase 3 cleavage and was secondary to phosphatidylinositol 3-kinase (PI3K)/Akt activation. CONCLUSION: Our findings indicate that levels of H2O2 increase during neutrophil influx and are necessary for the natural resolution of neutrophilic inflammation. Mechanistically, enhanced levels of H2O2 (endogenous or exogenous) inhibit p-Akt/NF-κB and induce apoptosis of migrated neutrophils. Modulation of H2O2 production may represent a novel strategy for controlling neutrophilic inflammation in the joints.
21081190 Osteoclasts in arthritis and Th17 cell development. 2011 May Bone destruction associated with rheumatoid arthritis (RA) is mainly attributed to the abnormal activation of osteoclasts, which are terminally differentiated cells of monocyte/macrophage lineage that resorb bone matrix. Studies on the immune regulation of osteoclasts in RA have promoted the new research field of "osteoimmunology", which investigates the interplay of the skeletal and immune systems at the molecular level. This interdisciplinary field is proving to be crucial to advances in the treatment of diseases associated with the bone and/or immune systems. As for the mechanisms of the bone destruction found in RA, accumulating evidence lends support to the theory that interleukin (IL)-17-producing helper T (Th17) cells induce the expression of receptor activator of nuclear factor-κB ligand (RANKL) in synovial cells, which in turn stimulates the differentiation and activation of osteoclasts together with inflammatory cytokines. Thus, inhibition of Th17 is potentially beneficial for the amelioration of the bone damage which occurs in RA. A recent study revealed that IκBζ is essential to the development of Th17 cells. These findings comprise an important advance in our understanding of the pathogenesis of RA and potentially effective therapeutic strategies.
21503617 Lack of cardiovascular risk assessment in inflammatory arthritis and systemic lupus erythe 2011 Oct The purpose of this study is to evaluate cardiovascular risk assessment at a Canadian rheumatology center and describe the cardiovascular risk of inflammatory arthritis (IA) and systemic lupus erythematosus (SLE) patients using the Framingham risk score. A retrospective chart review of 504 patients attending nine rheumatology practices at the University of Alberta Hospital was performed. A pre-specified case report form detailed patient demographics, cardiac risk factors, variables for the Framingham 2008 score, disease activity, and medication use. In this group of 504 patients, 64 (12.7%) had SLE (male (M) to female (F) ratio = 60:4) and 440 (87.3%) had an IA (M to F ratio = 117:323). Of the SLE patients, 31 (48.4%) met four or more American College of Rheumatology (ACR) criteria, 33 (51.6%) had less than four ACR criteria. Of the IA patients, 156 (35.5%) were CCP positive and 257 (58.4%) were RF positive. Utilizing the chart data, retrospective Framingham risk scores were calculable for one (1.6%) SLE patient and three (0.68%) IA patients. The most common cardiac risk factors not documented in the medical records of both the SLE and IA patients included: (1) positive family history of MI, (2) diabetes, and (3) lipid status. The blood pressure was more frequently documented in the SLE patients (93.8%) compared to the IA patients (56.1%). While traditional cardiac risk factors only partially contribute to the increased cardiovascular risk in these patients, cardiovascular risk assessment was suboptimally performed amongst a large group of rheumatologists. A dedicated cardiovascular risk reduction clinic for inflammatory rheumatic diseases has been established at this site to fulfill this need and evaluate treatment strategies.
22661644 Genetic markers of rheumatoid arthritis susceptibility in anti-citrullinated peptide antib 2012 Dec INTRODUCTION: There are now over 30 confirmed loci predisposing to rheumatoid arthritis (RA). Studies have been largely undertaken in patients with anticyclic citrullinated peptide (anti-CCP) positive RA, and some genetic associations appear stronger in this subgroup than in anti-CCP negative disease, although few studies have had adequate power to address the question. The authors therefore investigated confirmed RA susceptibility loci in a large cohort of anti-CCP negative RA subjects. METHODS: RA patients and controls, with serological and genetic data, were available from UK Caucasian patients (n=4068 anti-CCP positive, 2040 anti-CCP negative RA) and 13,009 healthy controls. HLA-DRB1 genotypes and 36 single nucleotide polymorphisms were tested for association between controls and anti-CCP positive or negative RA. RESULTS: The shared epitope (SE) showed a strong association with anti-CCP positive and negative RA, although the effect size was significantly lower in the latter (effect size ratio=3.18, p<1.0E-96). A non-intronic marker at TNFAIP3, GIN1/C5orf30, STAT4, ANKRD55/IL6ST, BLK and PTPN22 showed association with RA susceptibility, irrespective of the serological status, the latter three markers remaining significantly associated with anti-CCP negative RA, after correction for multiple testing. No significant association with anti-CCP negative RA was detected for other markers (eg, AFF3, CD28, intronic marker at TNFAIP3), though the study power for those markers was over 80%. DISCUSSION: In the largest sample size studied to date, the authors have shown that the strength of association, the effect size and the number of known RA susceptibility loci associated with disease is different in the two disease serotypes, confirming the hypothesis that they might be two genetically different subsets.
20424918 Association of polymorphisms in the human IL-10 and IL-18 genes with rheumatoid arthritis. 2011 Jan The decrease of anti-inflammatory cytokine and increase of pro-inflammatory cytokine was observed in rheumatoid arthritis (RA). Interleukin-10 (IL-10), a potent anti-inflammatory cytokine, has been demonstrated to suppress joint swelling and deformation in RA animal model. Interleukin-18 (IL-18), a widely distributed pro-inflammatory cytokine, induces the production of IFN-γ, activate NK cells, and promote inflammation. Recent studies demonstrated that the serum IL-10 and IL-18 levels may be influenced by genetics and related to susceptibility to several autoimmune diseases. In the present study, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing techniques, we analyzed the genotype and allele distributions of two single nucleotide polymorphisms (SNP) loci in the promoter region of IL-10 and IL-18 genes (IL-10-592 A/C and IL-18-607 A/C loci, respectively). Our results indicated that IL-10-592 allelic and genotypic frequencies were significantly different between the RA patients and normal subjects (P<0.05). In addition, significant differences of IL-10-592 allelic and genotypic frequencies were also detected between the patients with or without anti-cyclic citrullinated peptide antibody (anti-CCP) (P<0.05). In contrast, allelic and genotypic frequencies of IL-18-607 did not show significant difference between RA patients and normal subjects (P>0.05) or between anti-CCP-positive and anti-CCP-negative RA patients (P>0.05). Furthermore, ELISA detection of IL-10 and IL-18 serum levels revealed that the genotype of IL-10-592 was associated with IL-10 serum level (P<0.05), but the genotype and allele frequency of IL-18-607 was not associated with IL-18 serum level (P>0.05). Taken together, our findings provide new insight for the polymorphism of IL-10 gene in the pathogenesis of RA.
22012529 Early results of reverse shoulder arthroplasty in patients with rheumatoid arthritis. 2011 Oct 19 BACKGROUND: Rheumatoid arthritis affecting the shoulder is typically associated with rotator cuff compromise and can also result in severe glenoid erosion. Since reverse shoulder arthroplasty is capable of addressing both rotator cuff disorders and glenoid bone deficiencies, our aim was to evaluate the outcome of reverse shoulder arthroplasty in patients with rheumatoid arthritis and either or both of these associated conditions. METHODS: We performed eighteen primary reverse total shoulder arthroplasties in sixteen patients with rheumatoid arthritis involving the shoulder as well as associated rotator cuff compromise and/or severe erosion of the glenoid bone between 2002 and 2007. Patients were assessed with use of the Constant score, patient satisfaction score, subjective shoulder value, range of shoulder motion, and imaging studies. RESULTS: The mean Constant score improved from 22.5 to 64.9 points at a mean of 3.8 years (range, 2.1 to 7.0 years) postoperatively. The patients were either very satisfied or satisfied with the outcome of the surgery in seventeen of the eighteen shoulders. The mean subjective shoulder value was 68.6% postoperatively. Active forward elevation improved from 77.5° to 138.6°, and external rotation with the arm in 90° of abduction improved from 16.9° to 46.1°. The mean Constant score improved from 28.0 points to 74.3 points in shoulders in which the teres minor muscle was normal before the surgery, and it improved from 20.8 to 54.6 points in shoulders with an atrophic teres minor muscle. Scapular notching was observed in ten of the eighteen shoulders. A fracture involving the acromion, acromial spine, coracoid, or greater tuberosity was observed either intraoperatively or postoperatively in four of the eighteen shoulders. One case of transient axillary nerve injury was noted. There were no cases of dislocation, infection, or component loosening. None of the patients required revision surgery for any reason. CONCLUSIONS: Comparatively good outcomes were observed in the short to intermediate term after reverse shoulder arthroplasty in patients with rheumatoid arthritis. However, surgeons should be aware of the risk of intraoperative and postoperative fractures in this patient group.
22610149 Recombinant human endostatin inhibits adjuvant arthritis by down-regulating VEGF expressio 2012 Aug OBJECTIVE: The aim of this study was to examine the effect of recombinant human endostatin (rhEndostatin) on adjuvant arthritis (AA) in rats and its possible mechanisms. METHODS: RhEndostatin was subcutaneously administrated to AA rats after immunization. The progression of AA was assessed by the macroscopic arthritis scoring system of paws. Histological examination of the synovial tissues was examined by hematoxylin and eosin staining. The expression level of vascular endothelial growth factor (VEGF) mRNA and proteins in the synovial tissues was evaluated by realtime PCR and immunohistochemistry, respectively. Fibroblast-like synoviocytes (FLS) were isolated from synovial tissues. Cell proliferation assay was evaluateded with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. The levels of tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) in culture medium was examined by radioimmno assay. RESULTS: RhEndostatin attenuated the severity of arthritis on both second hind paw volume and polyarthritis score, as well as improved the arthritic status histologically in AA rats. Simultaneously, rhEndostatin can inhibit the expression of VEGF in synovial tissues. The proliferation of FLS and TNF-α, IL-1β production from culture medium was significantly inhibited by rhEndostatin. CONCLUSION: Our data suggest that rhEndostatin inhibits adjuvant arthritis by down-regulating VEGF expression and suppression of TNF-α, IL-1β production.
22740421 Adherence with bisphosphonate therapy in US veterans with rheumatoid arthritis. 2012 Dec OBJECTIVE: Pharmacy Benefits Management program data for patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were linked with clinical data to determine bisphosphonate adherence and persistence among US veterans with rheumatoid arthritis (RA) and to determine factors associated with adherence. METHODS: The primary outcome measures were the duration of bisphosphonate therapy and the medication possession ratio (MPR). Patients with an MPR <0.80 were classified as nonadherent. Potential covariates considered in the analysis included patient demographics, RA disease activity and severity parameters, and factors associated with osteoporosis risk. Associations of patient factors with duration of therapy and adherence were examined using multivariable regression modeling. RESULTS: Bisphosphonates were prescribed to 573 (41.5%) of 1,382 VARA subjects. The mean ± SD duration of therapy for bisphosphonates was 39.2 ± 31.4 months. A longer duration of therapy correlated with older age, more years of education, and dual x-ray absorptiometry testing. The mean ± SD MPR of VARA subjects for bisphosphonate therapy was 0.69 ± 0.28; 302 (52.7%) were nonadherent. In multivariate analyses, nonadherence with bisphosphonate therapy was associated with a longer duration of RA disease (odds ratio [OR] 1.02, 95% confidence interval [95% CI] 1.00-1.04) and duration of bisphosphonate therapy >32 months (OR 1.63, 95% CI 1.04-2.57). Whites were less likely to have a low MPR compared with nonwhites (OR 0.52, 95% CI 0.30-0.88). CONCLUSION: Nonadherence with bisphosphonates was common in this cohort of RA patients and was associated with nonwhite ethnicity, a longer duration of RA disease, and a greater duration of bisphosphonate therapy.
21501914 Systemic diseases and the pleura. 2011 Jul Pleural involvement in systemic diseases is usually a sign of lesions occurring at other levels. Despite the low incidence (around 1%) of pleural effusions caused by systemic diseases, more often connective tissue diseases, such as rheumatoid arthritis or systemic lupus erythematosus, may present with this. Similarly, vasculitis, such as Wegener's granulomatosis, Churg-Strauss syndrome, or less prevalent diseases, such as adult onset Still's disease, or human adjuvant disease, can also have pleural involvement. Although their incidence is low, it is important to take them into account when making a differential diagnosis of a pleural effusion. In this article, the systemic diseases that include pleural involvement are reviewed, as well as the characteristics of the effusions and their outcome.
21846359 CCR5Δ32 variant and cardiovascular disease in patients with rheumatoid arthritis: a cohor 2011 Aug 16 INTRODUCTION: The aim of our study was to analyze the influence of the CCR5Δ32 polymorphism in the risk of cardiovascular (CV) events and subclinical atherosclerosis among patients with rheumatoid arthritis (RA). METHODS: A total of 645 patients fulfilling the American Rheumatism Association 1987 revised classification criteria for RA were studied. Patients were genotyped for the CCR5 rs333 polymorphism using predesigned TaqMan assays. Also, HLA DRB1 genotyping was performed using molecular-based methods. Carotid intima-media thickness, flow-mediated endothelium-dependent dilatation (FMD) and endothelium-independent vasodilatation, which were used as surrogate markers of subclinical atherosclerosis, were measured in a subgroup of patients with no clinical CV disease. RESULTS: A lower frequency of carriers of the CCR5Δ32 allele among patients with CV events (3.4% versus 11.3%, P = 0.025, odds ratio 0.28, 95% confidence interval (95% CI) 0.06 to 0.89) was observed. However, after adjusting for gender, age at time of RA diagnosis, and the presence of shared epitope, rheumatoid factor and classic CV risk factors in the Cox regression analysis, this reduction of CV events in CCR5Δ32 allele carriers was slightly outside the range of significance (P = 0.097; hazard ratio 0.37 (95% CI 0.12 to 1.19)). Carriers of the CCR5Δ32 deletion also showed higher FMD values than the remaining patients (CCR5/CCR5Δ32 patients: 7.03% ± 6.61% versus CCR5/CCR5 patients: 5.51% ± 4.66%). This difference was statistically significant when analysis of covariance was performed (P = 0.024). CONCLUSIONS: Our results show a potential influence of the CCR5Δ32 deletion on the risk of CV disease among patients with RA. This may be due to a protective effect of this allelic variant against the development of vascular endothelial dysfunction.
20862678 Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment 2011 Jan OBJECTIVE: To determine whether cigarette smoking influences the response to treatment in patients with early rheumatoid arthritis (RA). METHODS: We retrieved clinical information about patients entering the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) early RA cohort from 1996 to 2006 (n=1,998) who were also in the Swedish Rheumatology Register (until 2007). Overall, 1,430 of the 1,621 registered patients were followed up from the time of inclusion in the EIRA cohort. Of these, 873 started methotrexate (MTX) monotherapy at inclusion, and 535 later started treatment with a tumor necrosis factor (TNF) inhibitor as the first biologic agent. The primary outcome was a good response according to the European League Against Rheumatism criteria at the 3-month visit. The influence of cigarette smoking (current or past) on the response to therapy was evaluated by logistic regression, with never smokers as the referent group. RESULTS: Compared with never smokers, current smokers were less likely to achieve a good response at 3 months following the start of MTX (27% versus 36%; P=0.05) and at 3 months following the start of TNF inhibitors (29% versus 43%; P=0.03). In multivariate analyses in which clinical, serologic, and genetic factors were considered, the inverse associations between current smoking and good response remained (adjusted odds ratio [OR] for MTX response 0.60 [95% CI 0.39-0.94]; adjusted OR for TNF inhibitor response 0.52 [95% CI 0.29-0.96]). The lower likelihood of a good response remained at later followup visits. Evaluating remission or joint counts yielded similar findings. Past smoking did not affect the chance of response to MTX or TNF inhibitors. Evaluating the overall cohort, which reflects all treatments used, current smoking was similarly associated with a lower chance of a good response (adjusted ORs for the 3-month, 6-month, 1-year, and 5-year visits 0.61, 0.65, 0.78, 0.66, and 0.61, respectively). CONCLUSION: Among patients with early RA, current cigarette smokers are less likely to respond to MTX and TNF inhibitors.
21288411 Preservation of lesser metatarsophalangeal joints in rheumatoid forefoot reconstruction. 2011 Feb BACKGROUND: A standard rheumatoid forefoot reconstruction consists of arthrodesis of the first metatarsophalangeal (MTP) joint and resection arthroplasty of the lesser metatarsal heads. However, preservation of the metatarsal heads has gained renewed interest since the medical treatment of rheumatoid arthritis has improved dramatically. MATERIAL AND METHODS: Nineteen consecutive patients with severe rheumatoid forefoot deformities underwent 24 forefoot reconstructions including first MTP arthrodesis with lesser MTP resection arthroplasty (resection arthroplasty group, ten feet), arthrolysis (arthrolysis group, six feet), or a combination of both (combined group, eight feet). Subjective, functional, and radiographic results were evaluated at 28 and 133 months (mean) followup. RESULTS: The overall AOFAS Forefoot Score at short- and long-term followup improved significantly (all p < 0.0001). There were no substantial differences between groups with regard to subjective rating, function, use of orthopaedic aids or shoewear, and walking capacity. Radiographic evaluation revealed a significant increase in axial malalignment of the lesser toes at long-term followup in all groups (all p < 0.018). Sagittal malalignment increased substantially in the resection arthroplasty group only. Reoperation rate was comparable among all groups, and a single third MTP arthrolysis (3%, 1/40) was converted to resection arthroplasty. CONCLUSION: In combination with first MTP arthrodesis, arthrolysis with preservation of all or only the lateral lesser MTP joints in rheumatoid forefoot reconstruction was a viable and durable alternative to resection arthroplasty when the joint destruction was mild to moderate.
21073280 IL-19, IL-20 and IL-24: potential therapeutic targets for autoimmune diseases. 2011 Feb IL-19, IL-20 and IL-24 are members of the IL-10 family of cytokines, the human IL-19, IL-20 and IL-24 genes are all located on the q32 region of chromosome 1, and the three cytokines also share a common receptor IL-20R1/IL-20R2 heterodimer. These cytokines due to the similarity and shared receptor usage, are quite overlapping in function. Recently, the available evidence has indicated that interaction of these cytokines with their receptors might exhibit pro-inflammatory effects on autoimmune diseases, particularly psoriasis and rheumatoid arthritis. Since an imbalance between anti- and pro-inflammatory cytokines contribute to the development of autoimune diseases, these cytokines may be implicated in the pathogenesis of autoimmunity. In this paper, we concisely discuss the biological features of IL-19, IL-20 and IL-24, and focus on their potential roles in autoimmune diseases. Hopefully the information obtained will lead to a better understanding of the pathogenesis and development of novel therapeutic strategies for autoimmune diseases.
22653018 [Osteoporosis secondary to various disorders]. 2012 Jun Secondary osteoporosis is caused by various disorders, metabolic derangements, and drug administration. Among causative disorders, primary hyperparathyroidism, rheumatoid arthritis, type 2 diabetes mellitus, and chronic kidney disease are prevalent ones. Fractures in type 2 diabetes and chronic kidney disease tend to result from the reduction in bone quality rather than that in bone mass.
20980704 Fcγ receptor IIIb polymorphism and use of glucocorticoids at baseline are associated with 2011 Feb OBJECTIVE: Infusion reaction is a major adverse event in patients with rheumatoid arthritis (RA) treated with infliximab. The possible factors including Fcγ receptor (FcγR) polymorphism associated with the development of infusion reactions in patients with RA receiving infliximab were prospectively examined. METHODS: 96 patients with RA were enrolled and scheduled to receive infliximab at a dose of 3 mg/kg at weeks 0, 2 and 6 and every 8 weeks thereafter. Genetic polymorphisms for FcγR were examined in FCGR3A 176F/V and FCGR3B NA1/2 alleles by allele-specific PCR analysis. RESULTS: An infusion reaction was observed in 17 patients (18%) during 52 weeks of treatment with infliximab. The FCGR3B NA1/NA1 genotype was found in 75% of the patients with infusion reactions and in only 37% of those without (p=0.01), whereas the FCGR3A 176F/V genotype was equally distributed in the patients with or without infusion reactions. Glucocorticoids were used in 53% of the patients who developed an infusion reaction and in 80% of those without an infusion reaction (p=0.02). A multivariable logistic regression model showed that the FCGR3B NA1/NA1 genotype and use of glucocorticoids at baseline could be used as independent predictive factors for infusion reactions (OR 6.1 (95% CI 1.9 to 24.3) and OR 0.26 (95% CI 0.08 to 0.84), respectively). The presence of anti-infliximab antibody during infliximab treatment was also associated with infusion reactions. CONCLUSION: FCGR3B NA1/NA1 genotype, use of glucocorticoids and the presence of anti-infliximab antibody accounted for nearly all patients with RA who developed infusion reactions.
22461888 Interaction analysis between HLA-DRB1 shared epitope alleles and MHC class II transactivat 2012 HLA-DRB1 shared epitope (SE) alleles are the strongest genetic determinants for autoantibody positive rheumatoid arthritis (RA). One of the key regulators in expression of HLA class II receptors is MHC class II transactivator (CIITA). A variant of the CIITA gene has been found to associate with inflammatory diseases.We wanted to explore whether the risk variant rs3087456 in the CIITA gene interacts with the HLA-DRB1 SE alleles regarding the risk of developing RA. We tested this hypothesis in a case-control study with 11767 individuals from four European Caucasian populations (6649 RA cases and 5118 controls).We found no significant additive interaction for risk alleles among Swedish Caucasians with RA (n = 3869, attributable proportion due to interaction (AP) = 0.2, 95%CI: -0.2-0.5) or when stratifying for anti-citrullinated protein antibodies (ACPA) presence (ACPA positive disease: n = 2945, AP = 0.3, 95%CI: -0.05-0.6, ACPA negative: n = 2268, AP = -0.2, 95%CI: -1.0-0.6). We further found no significant interaction between the main subgroups of SE alleles (DRB1*01, DRB1*04 or DRB1*10) and CIITA. Similar analysis of three independent RA cohorts from British, Dutch and Norwegian populations also indicated an absence of significant interaction between genetic variants in CIITA and SE alleles with regard to RA risk.Our data suggest that risk from the CIITA locus is independent of the major risk for RA from HLA-DRB1 SE alleles, given that no significant interaction between rs3087456 and SE alleles was observed. Since a biological link between products of these genes is evident, the genetic contribution from CIITA and class II antigens in the autoimmune process may involve additional unidentified factors.
22127692 Blood memory B cells are disturbed and predict the response to rituximab in patients with 2011 Dec OBJECTIVE: To examine blood B cell subsets in patients with rheumatoid arthritis (RA) prior to B cell depletion therapy and to assess their potential as predictors of clinical response to rituximab (RTX). METHODS: Blood B cell subsets were assessed by flow cytometry in 208 RA patients included in an RTX retreatment study (assessed prior to RTX treatment) and in 47 age-matched controls. Expression of BAFF receptor (BAFF-R) on B cells and serum B cell biomarkers was also measured. B cell subsets and BAFF-R expression were compared between RA patient and control populations. Univariate and multivariate analyses were performed to identify baseline factors associated with a European League Against Rheumatism response 24 weeks after 1 cycle of RTX. RESULTS: Mean ± SD counts of both CD27- naive and CD27+ memory B cells were decreased in RA patients (188.6 ± 121.4/mm(3)) compared with controls (257.3 ± 154.1/mm(3)) (P = 0.001) and were partially restored in patients treated with methotrexate (MTX) plus anti-tumor necrosis factor compared with patients treated with MTX alone. Within the CD27+ memory B cells, the CD27+IgD- switched memory subtype was selectively decreased, irrespective of treatment. The frequency of CD27+ memory B cells correlated inversely with levels of several B cell activation biomarkers in RA. Serum BAFF level and BAFF-R expression was comparable in RA patients and controls. A low baseline CD27+ memory B cell frequency was associated with a greater clinical response to RTX (odds ratio 0.97 [95% confidence interval 0.95-0.99], P = 0.0015). CONCLUSION: In B cell depletion therapy-naive RA patients, a low frequency of CD27+ memory B cells correlated with levels of serum B cell activation biomarkers and may predict response to RTX. These results suggest that low memory B cell frequency may be indicative of a B cell-driven RA subtype that is more sensitive to B cell depletion therapy.
23327519 Implications for managed care and specialty pharmacy in rheumatoid arthritis. 2012 Dec Treatment of rheumatoid arthritis (RA) can be very costly. Cost-effectiveness studies provide insight into the value of treatment from a number of perspectives (eg, societal, healthcare). In most cases, the indirect costs of RA can offset the direct costs in 2 ways. Prevention of disease progression can limit future costs, such as those related to surgery and hospitalization. When disease progression is minimized, patients feel better and can have improved work productivity. Disease control of RA has improved over time, and this is attributed primarily to the introduction of more effective therapies. Despite the effectiveness of new therapies, there are a number of barriers to optimal treatment. Barriers include lack of education for patients and practitioners about RA, poor patient-provider communication, uncertainty regarding which treatments to choose, cost, and lack of adherence. Specialty pharmacy and disease therapy management programs can assist patients by providing structure, education, and mechanisms to improve treatment adherence and persistence to optimize therapy.
20020141 Which is the dominant factor for perception of rheumatic pain: meteorology or psychology? 2011 Mar It is believed that there is an association between the weather and rheumatic symptoms. We aimed to investigate what kind of association is present and what are the factors which determine the nature of this association. Fifty-six subjects with rheumatic disease (31 RA, 15 SpA, 10 OA) who live in Antalya were followed between December 2005 and July 2006. Patients were asked to fill diaries which contain questions regarding the symptoms of their rheumatic diseases everyday. In every monthly visit, disease activity measurement, laboratory assessment and Beck depression inventory assessment were recorded. The symptomatic and psychological measurements were matched with the meteorological data of Antalya Regional Directorate of Meteorological Service of Turkish State. Correlation of symptoms with weather variables was investigated. Contributory effect of weather and of psychologic factors on symptom scores were evaluated by stepwise multiple regression analysis. Eighty-four percent of subjects belive in an association between weather and rheumatism, while 57% claimed to have ability to forecast weather. The maximum correlation coefficient between weather and arthritis symptoms was -0.451 and the maximum contribution of weather on symptoms was 17.1%. Arthritis symptoms were significantly contributed by Beck depression score. The belief about presence of weather-arthritis association was found to be stronger than its statistical power. Our results did not prove or rule out the presence of weather-rheumatism association. As long as the scientific attempts result in failure, the intuitive support in favour of the presence of weather-arthritis association will go on forever.