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ID PMID Title PublicationDate abstract
21303479 Clinical factors related to the efficacy and complications of orthopedic surgery for rheum 2011 Feb AIMS: To determine what clinical factors relating to efficacy besides complications of orthopedic surgery for patients treated with anti-tumor necrosis factor (TNF)-α therapy (infliximab), we analyzed the clinical data of 52 cases of orthopedic surgery, such as total hip arthroplasy (THA), total knee arthroplasty (TKA), total shoulder arthroplasy (TSA), total elbow arthroplasty (TEA), arthroscopic synovectomy, foot arthroplasty, spine surgery, hand surgery and fracture. METHODS: We analyzed clinical factors including age, disease duration, preoperative C-reactive protein (CRP), disease activity score (DAS)-28, matrix metalloproteinase (MMP)-3, and rheumatoid arthritis particle-agglutination (RAPA) in 52 cases of rheumatoid arthritis (RA) undergoing orthopedic surgery. For complications of orthopedic surgery, signs of postoperative infection were recorded, including rubor, discharge, systemic infection and frequencies of wound dehiscence, as well as the incidence of any surgical complication requiring a secondary revision procedure were measured. RESULTS: Signs of infection or surgical complications occurred in two of 52 patients (3.8%). There is significant correlation between RAPA and improvement of CRP 3 months after surgery; however, there is no correlation between infection and clinical factors including age, disease duration, preoperative CRP, MMP-3, RAPA and the period until surgery after infliximab infusion. CONCLUSION: Infliximab did not increase the risk of either infections or surgical complications occurring in patients with RA within 1 year of orthopedic surgery. Improvement of CRP after surgery is likely to be due to infliximab for high RAPA in RA patients.
21284489 Attenuation of oxidative stress by allylpyrocatechol in synovial cellular infiltrate of pa 2011 May Free radicals are involved in the pathogenesis of Rheumatoid arthritis, a systemic autoimmune disorder characterized by unchecked synovial inflammation. Allylpyrocatechol, a phytoconstituent of Piper betle leaves, has potent anti-inflammatory activity and this study evaluated its anti-oxidant effect on the synovial infiltrate of patients with Rheumatoid arthritis. The ex vivo effect of allylpyrocatechol upon generation of reactive oxygen species in neutrophils, macrophages and lymphocytes was measured by flow cytometry using dichlorodihydrofluorescein diacetate, wherein it significantly decreased basal levels as also scavenged phorbol myristate acetate generated reactive oxygen species. Furthermore, its effect on generation of superoxide and hydroxyl radicals produced within infiltrated neutrophils was measured by cytochrome c and deoxyribose assay, respectively. Allylpyrocatechol significantly scavenged superoxide and hydroxyl radicals in infiltrated neutrophils. The effect of allylpyrocatechol on nitric oxide was measured in macrophages using 4,5-diaminofluorescein diacetate by flow cytometry wherein it decreased production of nitric oxide in infiltrated macrophages, which correlated with its in vitro nitric oxide scavenging activity. Taken together, this ex vivo study has established that allylpyrocatechol has potent scavenging activity and could be considered as an add-on therapy in the treatment of inflammation-associated disorders like Rheumatoid Arthritis.
23070645 New developments in osteoimmunology. 2012 Nov Investigations into interactions between the skeletal and immune systems were developed during research into arthritis, with characterization of T-cell-mediated regulation of osteoclastogenesis. A new interdisciplinary field--osteoimmunology--was created, and has since expanded to encompass disciplines including signal transduction, stem cell niches and fundamental immunology. We have witnessed rapid progress in understanding the mechanisms of bone damage in arthritis and the roles of immune molecules in bone, but comparatively less evidence has been provided for the role of bone-derived factors in the immune system. Nevertheless, regulation of immune cells, including haematopoietic stem cells, by bone cells is now a hot topic in this field. Here, I discuss recent advances in osteoimmunology and emerging avenues of basic and clinical investigation.
21378108 Subclinical remodelling of draining lymph node structure in early and established rheumato 2011 Aug OBJECTIVE: To investigate the suitability of power Doppler ultrasonography (PD-US) for the assessment of lymph node (LN) status in RA, evaluating the existence of structural and dynamic modifications in well-characterized stages of the disease. METHODS: Ten patients with active disease and five patients in clinical remission underwent complete clinical and PD-US examination of hands, wrists, axillary and cervical LNs on the same day. Synovitis and PD were graded 0-3. LN assessment included maximum short axis, cortical hypertrophy (CH) and PD signal distribution. All patients with active disease were re-evaluated prospectively 3 months after initiation of therapy. RESULTS: PD-US signs of axillary LN remodelling were observed in 7 out of 10 patients with active disease despite the absence of clinical lymphoadenopathy. Subclinical alterations were detected in both early untreated RA and in established disease. Characteristic structural changes consisted of hypertrophy of the LN cortex and PD signal amplification in cortical and hilar regions. Cervical LNs in active disease and axillary LNs in clinical remission were unaffected. LN PD amplification returned to normal ranges in patients with baseline alterations re-evaluated 3 months after therapy with TNF-α blocking agents and/or MTX. CONCLUSION: Draining LNs in RA are subjected to subclinical intra-parenchymal changes and vascular flow modulation detectable by PD-US. Sonographic signs of LN involvement associate with disease activity and are reversible upon treatment. These data point at LN reactivity as a dynamic component of RA inflammatory cascade and an attractive platform to be explored in prognostic and response to therapy evaluations.
21784730 Risk of septic arthritis in patients with rheumatoid arthritis and the effect of anti-TNF 2011 Oct OBJECTIVES: To evaluate the risk of septic arthritis (SA) in patients with rheumatoid arthritis (RA) treated with anti-tumour necrosis factor (TNF) therapy. METHODS: Using data from the British Society for Rheumatology Biologics Register, a prospective observational study, the authors compared the risk of SA between 11 881 anti-TNF-treated and 3673 non-biological disease-modifying antirheumatic drug (nbDMARD)-treated patients. RESULTS: 199 patients had at least one episode of SA (anti-TNF: 179, nbDMARD: 20). Incidence rates were: anti-TNF 4.2/1000 patient years (pyrs) follow-up (95% CI 3.6 to 4.8), nbDMARD 1.8/1000 pyrs (95% CI 1.1 to 2.7). The adjusted HR for SA in the anti-TNF cohort was 2.3 (95% CI 1.2 to 4.4). The risk did not differ significantly between the three agents: adalimumab, etanercept and infliximab. The risk was highest in the early months of therapy. The patterns of reported organisms differed in the anti-TNF cohort. Prior joint replacement surgery was a risk factor for SA in all patients. The rate of postoperative joint infection (within 90 days of surgery) was 0.7%. This risk was not significantly influenced by anti-TNF therapy. CONCLUSIONS: Anti-TNF therapy use in RA is associated with a doubling in the risk of SA. Physicians and surgeons assessing the RA patient should be aware of this potentially life-threatening complication.
21345294 Sustained improvement of health-related quality of life in patients with early rheumatoid 2011 Jan OBJECTIVES: To assess long-term impact of RA on the HR-QoL in a cohort of working-age patients with early disease treated by a multidisciplinary team including early and active use of disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Fifty-five consecutive patients with RA who were naïve to DMARDs and glucocorticoids were assessed at baseline and at 6 months, 1, 2, 5 and 10 years. HR-QoL, disease activity, function, and joint destruction of hands and feet were assessed by using the Nottingham Health Profile (NHP) instrument, the 28-joint based Disease Activity Score (DAS28), the Health Assessment Questionnaire (HAQ), and the Larsen scores, respectively. GEE (generalised estimation equations)-method was used to evaluate longitudinal relationships between the HR-QoL changes and other variables. RESULTS: All NHP dimensions except social isolation improved significantly during the first six months and remained favourable up to 10 years. The most prominent improvements were seen in the dimensions for pain and emotional reaction (p<0.001). In longitudinal evaluation statistically significant associations (p<0.001) were found between the DAS28 and the NHP dimensions for pain, energy and emotional reaction, and between the HAQ and the NHP dimensions for pain, energy and mobility. The extent of joint damage had no statistically significant associations to the six dimensions of the NHP instrument. CONCLUSIONS: Early improvements in HR-QoL carried over the ten-year follow-up in patients with recent-onset RA treated with a multidisciplinary strategy including early and active DMARD therapy. HR-QoL changes were longitudinally associated especially with disease activity and function.
23047532 Treatment of early rheumatoid arthritis in a multinational inception cohort of Latin Ameri 2012 Oct BACKGROUND: Treatment of rheumatoid arthritis (RA) has evolved dramatically in the last decade. However, little is known about the way rheumatologists in Latin America treat their patients in clinical practice, outside the scope of clinical trials. OBJECTIVE: The objective of this study was to describe treatment patterns at disease onset in early RA with data from a large, multicenter, multinational inception cohort of Latin American patients. METHODS: Consecutive patients with early RA (<1 year of disease duration as diagnosed by a rheumatologist) from 46 centers in 14 Latin American countries were enrolled in the study. Clinical data, laboratory assessments, and a detailed registry on type of prescriptions were collected at baseline and at 3, 6, 12, 18, and 24 months of follow-up. Hands and feet x-rays were obtained at baseline and at 12 and 24 months. All data were captured in Arthros 6.1 database. Continuous variables were expressed as means and SDs, and categorical variables were expressed as percentages and 95% confidence intervals (95% CIs). Only therapeutic data at baseline are presented, corresponding to the period between disease onset and second visit (3 months). RESULTS: A total of 1093 patients were included. Eighty-five percent were female, and 76% had a positive rheumatoid factor. Mean age at diagnosis was 46.5 (SD, 14.2) years, and mean disease duration at the first visit was 5.8 (SD, 3.8) months. Between baseline and second visit (3 months), 75% of patients (95% CI, 72%-78%) received disease-modifying antirheumatic drugs. Methotrexate (MTX) alone or in combination was the most frequently used (60.5%), followed by antimalarials (chloroquine or hydroxychloroquine, 32.1%), sulfasalazine (7.1%), and leflunomide (LEF, 4%). In 474 patients (43%), initiation of disease-modifying antirheumatic drugs was within the first month after the first visit. In addition, 290 patients (26%; 95% CI, 23%-29%) received combination therapy as initial treatment. The most frequently used combinations were MTX + chloroquine (45%), MTX + hydroxychloroquine (25%), and MTX + sulfasalazine (16%). Eleven patients (1%; 95% CI, 0.5%-1.8%) received biologics. Sixty-four percent (95% CI, 60%-66%) received corticosteroids. Of those, 80% (95% CI, 77%-84%) received 10 mg of oral prednisone or less. CONCLUSIONS: In this cohort of Latin American patients with early RA, most patients received MTX very early in their disease course. Combination therapy was used approximately in 1 of every 4 patients as initial therapy. Biologics were rarely used at this early stage, and low-dose prednisone was commonly used.
22443994 The rheumatoid foot and ankle: current evidence. 2012 Jun The management of rheumatoid patients is a complex process due to the chronic, systemic, multi-joint and extra-articular nature of the disease. In comparison, osteoarthritis and post-traumatic arthritis usually involve a single joint and are hence not comparable to rheumatoid pathology. This review sets out to specifically look at studies on rheumatoid patients with interventions for foot or ankle disease. MEDLINE, EMBASE, the Cochrane databases, Current Controlled Trials and the WHO International Clinical Trials Registry Platform are all searched for relevant studies.
23129416 A case-control study on the association between rheumatoid arthritis and bladder pain synd 2013 Sep AIM: While bladder pain syndrome/interstitial cystitis (BPS/IC) has been suggested by a number of studies to have autoimmune character, no population-based study to date has been conducted investigating its association with rheumatoid arthritis (RA). This study aimed to examine the association between IC/BPS and having previously been diagnosed with RA. METHODS: We conducted this study by using administrative claims data sourced from the Taiwan National Health Insurance Database. Our study included 9,269 cases with BPS/IC and 46,345 randomly selected controls. Conditional logistic regression was performed to calculate the odds ratio (OR) for the association between previously diagnosed RA and IC/BPS. RESULTS: RA was found among 202 (2.2%) cases and 504 (1.12%) controls. Conditional logistic regression analysis suggested that when compared with controls, the OR for prior RA among cases was 1.66 (95% CI = 1.47-1.87, P < 0.001) after adjusting for diabetes, hypertension, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraine, sicca syndrome, allergy, endometriosis, asthma, overactive bladder, tobacco use disorder, and alcohol abuse. Additionally, BPS/IC was consistently and significantly associated with a previous diagnosis of RA regardless of prescription drug use; the OR for prior RA among groups prescribed ≤1 type of disease-modifying antirheumatic drug (DMARD), two types of DMARDs, and ≥3 types of DMARDs or TNF-alpha inhibitor when compared to controls were 1.49 (95% CI = 1.28-1.72), 1.91 (95% CI = 1.38-2.68), and 2.36 (95% CI = 1.77-3.17), respectively. CONCLUSIONS: There is an association between RA and BPS/IC after adjusting for socio-demographic characteristics and medical co-morbidities.
22753659 The carotid artery atherosclerosis burden and its relation to cardiovascular risk factors 2012 Sep OBJECTIVE: Black Africans currently experience a distinctly low frequency of atherosclerotic cardiovascular disease. Whether this protection persists in those with rheumatoid arthritis (RA) is unknown. We compared the carotid atherosclerosis burden and its relationships with cardiovascular (CV) risk factors between Africans with RA from a developing black and developed CV population. METHODS: We performed high resolution B-mode ultrasonography and assessed CV risk factors in 243 patients with established RA, of whom 121 were black and 122 white. Data were analyzed in age, sex, and healthcare center-adjusted regression models. RESULTS: The mean±SD common carotid intima-media thickness (cIMT) was 0.694±0.097 mm in black and 0.712±0.136 mm in white patients (adjusted p=0.8). Plaque prevalence was also similar in black compared to white cases (35.5% and 44.3%, respectively; adjusted OR 0.83, 95% CI 0.32-2.20, p=0.7). Interactions between population grouping and several CV risk factors were independently associated with cIMT and plaque. In stratified analysis, that is, in each population group separately, risk factors associated with cIMT or/and plaque comprised the systolic blood pressure (p=0.02), serum cholesterol/high-density lipoprotein cholesterol ratio (p=0.004), C-reactive protein concentrations (p=0.01), and the presence of extraarticular manifestations (p=0.01) in whites but, contrastingly, the Arthritis Impact Measurement Scales tension score (p=0.04) and use of nonsteroidal antiinflammatory agent (p=0.03) in black patients. The Framingham score was significantly associated with atherosclerosis only in whites (p<0.0001). CONCLUSION: The carotid atherosclerosis burden is similar in black compared to white Africans with RA, but relationships between modifiable CV risk factors and atherosclerosis vary substantially among Africans with RA.
22336440 Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Do 2012 Feb 15 INTRODUCTION: Biological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultrasonographic (US) outcomes in patients with recent-onset RA. METHODS: The study included 161 early RA patients (disease duration < 12 months) treated according to a disease activity score (DAS) driven step-up protocol aiming at DAS < 2.4. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of the hands was performed at baseline, 6 and 12 months. Grey-Scale (GS) and Power Doppler (PD) synovitis were scored (0 to 3), with overall scores as the sum of each joint score. CXCL13 levels were measured at baseline by enzyme-linked immunosorbent assay and evaluated in relation to the achievement of low disease activity (LDA, DAS < 2.4) and US residual inflammation (PD ≤ 1) at 12 months. RESULTS: Baseline levels of CXCL13 were significantly higher in RA compared to healthy controls (n = 19) (P = 0.03) and correlated with measures of synovitis, such as the swollen joint count (R 0.28, P < 0.001), the US-GS (R 0.27, P = 0.003) and US-PD (R 0.26, P = 0.005) score. Although CXCL13 did not predict the likelihood of achieving clinical LDA at 12 months within a structured treat-to-target protocol, elevated levels of CXCL13 were associated with more frequent increases of methotrexate dosage (P < 0.001). Using adjusted analyses, the highest levels of CXCL13 (> 100 pg/ml) were the only independent predictor of residual imaging inflammation (P = 0.005), irrespective of initial US-PD scores, disease activity status, acute phase reactants and autoantibodies. Among the patients in clinical LDA at 12 months, US-PD scores ≤ 1 were less frequently achieved in the high baseline CXCL13 (> 100 pg/ml) group, with an adjusted OR = 0.06 (95% CI 0.01 to 0.55, P = 0.01). CONCLUSIONS: CXCL13 emerges as a new biological marker in early RA, accurate in assessing the severity of synovitis and the persistence of US-PD activity over time in response to conventional treatments.
22150003 Immunotherapeutic implication of IL-6 blockade. 2012 Jan IL-6 is a cytokine featuring redundancy and pleiotropic activity. While IL-6 contributes to host defense against acute environmental stress, continuous IL-6 production plays a significant pathological role in various autoimmune and chronic inflammatory diseases. To counter this drawback, tocilizumab, a humanized anti-IL-6 receptor antibody, was developed. Clinical trials have verified the efficacy of tocilizumab for patients with rheumatoid arthritis, Castleman's disease and systemic juvenile idiopathic arthritis, resulting in approval of this innovative biologic for their treatment. Moreover, a considerable number of case reports and pilot studies have indicated the beneficial effects of tocilizumab on other autoimmune and chronic inflammatory diseases. Further clinical studies to evaluate the efficacy and safety of tocilizumab for these diseases are essential.
22040493 Rs548234 polymorphism at PRDM1-ATG5 region susceptible to rheumatoid arthritis in Caucasia 2011 Sep BACKGROUND: A previous study has shown that rs548234 polymorphism at PRDM1-ATG5 region is associated with rheumatoid arthritis (RA) in Caucasian populations. The aim of this study was to investigate the effect of rs548234 polymorphism at PRDM1-ATG5 region on susceptibility to RA in Chinese Han population. METHODS: We genotyped 848 RA patients and 1431 matched healthy controls for rs548234 single-nucleotide polymorphism (SNP) with a predesigned TaqMan SNP genotyping assay. Association analyses were performed on the whole data set and on rheumatoid factors (RF) and anti-cyclic citrullinated peptides (anti-CCP) antibody. Finally, we carried out combined analysis of rs548234 association with RA based on the published data. RESULTS: No significant difference in the genotype distribution between RA patients and healthy controls for rs548234 (C/T) polymorphism was found in Chinese Han population, neither in whole data set nor in stratified subsets, e.g. RF and anti-CCP status. Association analysis in different ethnic groups showed that rs548234 at PRDM1-ATG5 region was associated with RA in Caucasian ancestry but not in East Asian population. CONCLUSIONS: Our results showed no involvement of rs548234 at PRDM1-ATG5 region in the susceptibility or clinical relevance of RA in Chinese Han population.
21964730 Frequency-domain optical tomographic imaging of arthritic finger joints. 2011 Oct We are presenting data from the largest clinical trial on optical tomographic imaging of finger joints to date. Overall we evaluated 99 fingers of patients affected by rheumatoid arthritis (RA) and 120 fingers from healthy volunteers. Using frequency-domain imaging techniques we show that sensitivities and specificities of 0.85 and higher can be achieved in detecting RA. This is accomplished by deriving multiple optical parameters from the optical tomographic images and combining them for the statistical analysis. Parameters derived from the scattering coefficient perform slightly better than absorption derived parameters. Furthermore we found that data obtained at 600 MHz leads to better classification results than data obtained at 0 or 300 MHz.
21706263 Etanercept in combination with conventional disease-modifying antirheumatic drugs (DMARDs) 2012 Feb Although etanercept (ETN) is effective when used in monotherapy for the treatment of rheumatoid arthritis (RA), ETN/methotrexate (MTX) combination therapy is more efficacious. However, some patients show MTX intolerance; these patients may develop adverse events (AEs) or have risk factors for AEs. There is limited published information regarding the efficacy of combination therapy involving ETN and disease-modifying antirheumatic drugs other than MTX. Therefore, we evaluated the effects of combination therapy with ETN and salazosulfapyridine (SASP) and/or bucillamine (Bc), a D: -penicillamine analogue, in MTX-intolerant RA patients. Indices of RA activity, including disease activity score in 28 joints (DAS28), were retrospectively analyzed over a 48-week period in 66 patients treated with ETN. Treatment efficacy was compared in the following 4 major treatment groups: ETN monotherapy, ETN + MTX, ETN + SASP, and ETN + SASP + Bc. Although intergroup differences in the percent change of DAS were not statistically significant, ETN + SASP + Bc seemed to be more effective than ETN monotherapy, and the efficacy of ETN + SASP + Bc was comparable to that of ETN + MTX according to the European League Against Rheumatism (EULAR) improvement ratings. These results suggest that ETN + SASP + Bc combination therapy may be a viable option for RA treatment in patients in whom MTX cannot be used.
21956827 [Prophylaxis and treatment of osteoporosis in patients with rheumatoid arthritis (ORA stud 2011 Nov OBJECTIVE: The aim of this study was to examine bone mineral density (BMD), frequency of osteopenia and osteoporosis in a representative sample of patients with rheumatoid arthritis (RA) and to describe chemoprophylaxis and treatment of osteoporosis compared to evidence-based guidelines. PATIENTS AND METHODS: In 2005 and 2006, 532 patients with RA (98 men, 434 women) aged 23-87 years were recruited from 9 German rheumatology centers. Clinical examination included a detailed documentation of osteoporosis medication. Dual-energy X-ray absorptiometry (DXA) was used to measure BMD at the lumbar spine and femoral neck. Osteopenia and osteoporosis were defined according to the criteria of the World Health Organization. RESULTS: Of the RA patients 29% had normal BMD at the spine and femoral neck, 49% of the patients had osteopenia and 22% met the criteria for osteoporosis at any site. Of the patients 60% were receiving medication for prophylaxis or therapy of osteoporosis, 38% calcium/vitamin D alone, 20% as combinations mostly of calcium/vitamin D + bisphosphonate, 1% received bisphosphonate only and 1% hormone replacement therapy. Although the frequency of osteoporosis showed no significant differences between male and female patients, women with RA used osteoporosis medication more often than men (63% versus 49%, χ²-test, p <0.05). A total of 101 RA patients (83 menopausal women, 6 premenopausal women, 12 men) received corticosteroids in a daily dose of 7.5 mg or less for at least 3 months and had DXA T-scores below -2.0 at any site. In this patient group 41% of the menopausal women, 17% of the premenopausal women and 42% of the male patients were reported to receive medication with calcium/vitamin D + bisphosphonate. Calcium/vitamin D was used by 35% of the menopausal women, none of the premenopausal women and 50% of the male patients and 18% of the menopausal women, 67% of the premenopausal women and 8% of men received no prophylaxis or treatment for osteoporosis. CONCLUSION: According to the DVO (German Society for Osteoporosis) guidelines for osteoporosis (2009) menopausal women with corticosteroid therapy < 7.5 mg per day for at least 3 months and DXA T-scores below -2.0 should receive treatment with bisphosphonate and calcium/vitamin D. The data show that there were still deficits concerning prophylaxis and treatment of osteoporosis in RA.
22984268 ZAP-70+ B cell subset influences response to B cell depletion therapy and early repopulati 2012 Dec OBJECTIVE: To define the role of ZAP-70+ B cells (CD19+/ZAP-70+) as a biomarker of response to B cell depletion therapy (BCDT), their relationship with clinical outcome, and their behavior during repopulation of peripheral blood in patients with rheumatoid arthritis (RA). METHODS: Thirty-one patients with RA underwent BCDT and were followed for 12 months. Disease activity was assessed with the European League Against Rheumatism (EULAR) criteria. Cytofluorimetric analysis of peripheral blood B cell subsets at baseline and at 6- and 12-month intervals after BCDT was performed using surface markers (CD45, CD3, CD56, CD19, IgD, CD38, CD27) and intracellular ZAP-70. RESULTS: A moderate/good EULAR response was achieved in 66.6% of the RA cohort. The baseline percentage of CD19+/ZAP-70+ cells was lower in good responder patients (1.8% ± 1.7%) compared to poor responders (5.6% ± 4.9%; p = 0.02). A decrease of plasmablasts (IgD-CD27+CD38+) and pre-switch memory (IgD+CD27+) B cells occurred after BCDT. Recovery of B cells in peripheral blood after the first course of BCDT was characterized by the reappearance of B cell subtypes that showed a naive, activated phenotype, coupled with a decrease in memory cells. B cells carrying intracytoplasmic ZAP-70 increased significantly from the baseline value of 4.4% ± 4.5% to 12.4% ± 9.2% (p = 0.001) at the 6-month and to 9.4% ± 6.4% (p = 0.002) at the 12-month followup. CONCLUSION: Baseline percentage of CD19+/ZAP-70+ cells is associated with the clinical outcome after BCDT in patients with RA. Depletion of plasmablasts and pre-switch memory B cells and increase of CD19+/ZAP-70+ cells are features of the recovery of the B cell pool after BCDT.
21454307 Optimal care for early RA patients: the challenge of translating scientific data into clin 2011 Jul Although the evidence is clear and most rheumatologists agree that RA should be treated early and intensively, it obviously remains a challenge to put this paradigm into practice. Patient- as well as physician-related factors determine the delay before the disease is recognized and treated appropriately. There is still a need for education in this context. Optimal treatment allocation depends on the determination of prognostic factors, but should also take into account the patient's perspective to be effective. Patients' perceptions about the disease and its medical management need to be adjusted as soon as possible. Initiation of intensive or complex treatment regimens is most feasible in a clinical setting, where rheumatologists work together with other health-care professionals, such as nurse specialists. Until now there does not seem to have been a difference in terms of efficacy between intensive RA treatment strategies based on a combination of classical DMARDs with glucocorticoids or with TNF-blocking agents, but given the costs biologicals cannot be considered first-line therapy. More scientific work is needed to identify individuals that could benefit from biologicals early in the disease. Given the long-term benefits of rapid disease control, health authorities should consider investing in a better implementation of intensive treatment regimens based on combinations of classical DMARDs and glucocorticoids.
22555227 Rosuvastatin might have an effect on C-reactive protein but not on rheumatoid disease acti 2012 May The aim of this study was to study the effects of rosuvastatin in patients with rheumatoid arthritis (RA) looking at the C-reactive protein (CRP), interleukin-6 (IL-6) and joint disease activity. Fifty RA patients were randomized in a double-blind placebo-controlled trial to receive either 10 mg of rosuvastatin or placebo as an adjunct to existing disease-modifying antirheumatic therapy. Patients were followed up for a six-month period. Measurements were done at baseline and six months. CRP and IL-6 were measured in the blood. RA disease activity was measured using disease activity score based on 28 joint counts (DAS 28). When analysing from baseline to six months there was no difference between the rosuvastatin and placebo groups in rheumatoid disease activity (-0.01; standard deviation [SD], 1.08; and +0.18; SD, 0.95; respectively; P value 0.509). There was a trend towards improvement in CRP in the rosuvastatin group (-3.23; SD, 18.18) compared with the placebo group (+17.43; SD, 38.03); P value, 0.161. IL-6 showed a trend towards worsening in the rosuvastatin group (+0.15; SD, 1.09) compared with placebo (-0.73; SD, 1.4); P value, 0.054. These data show that rosuvastatin with might decrease the CRP independent to IL-6 in patients with RA but does not improve the overall rheumatoid disease activity.
22366959 Pre-analytical effects of blood sampling and handling in quantitative immunoassays for rhe 2012 Apr 30 Variability in pre-analytical blood sampling and handling can significantly impact results obtained in quantitative immunoassays. Understanding the impact of these variables is critical for accurate quantification and validation of biomarker measurements. Particularly, in the design and execution of large clinical trials, even small differences in sample processing and handling can have dramatic effects in analytical reliability, results interpretation, trial management and outcome. The effects of two common blood sampling methods (serum vs. plasma) and two widely-used serum handling methods (on the clot with ambient temperature shipping, "traditional", vs. centrifuged with cold chain shipping, "protocol") on protein and autoantibody concentrations were examined. Matched serum and plasma samples were collected from 32 rheumatoid arthritis (RA) patients representing a wide range of disease activity status. Additionally, a set of matched serum samples with two sample handling methods was collected. One tube was processed per manufacturer's instructions and shipped overnight on cold packs (protocol). The matched tube, without prior centrifugation, was simultaneously shipped overnight at ambient temperatures (traditional). Upon delivery, the traditional tube was centrifuged. All samples were subsequently aliquoted and frozen prior to analysis of protein and autoantibody biomarkers. Median correlation between paired serum and plasma across all autoantibody assays was 0.99 (0.98-1.00) with a median % difference of -3.3 (-7.5 to 6.0). In contrast, observed protein biomarker concentrations were significantly affected by sample types, with median correlation of 0.99 (0.33-1.00) and a median % difference of -10 (-55 to 23). When the two serum collection/handling methods were compared, the median correlation between paired samples for autoantibodies was 0.99 (0.91-1.00) with a median difference of 4%. In contrast, significant increases were observed in protein biomarker concentrations among certain biomarkers in samples processed with the 'traditional' method. Autoantibody quantification appears robust to both sample type (plasma vs. serum) and pre-analytical sample collection/handling methods (protocol vs. traditional). In contrast, for non-antibody protein biomarker concentrations, sample type had a significant impact; plasma samples generally exhibit decreased protein biomarker concentrations relative to serum. Similarly, sample handling significantly impacted the variability of protein biomarker concentrations. When biomarker concentrations are combined algorithmically into a single test score such as a multi-biomarker disease activity test for rheumatoid arthritis (MBDA), changes in protein biomarker concentrations may result in a bias of the score. These results illustrate the importance of characterizing pre-analytical methodology, sample type, sample processing and handling procedures for clinical testing in order to ensure test accuracy.