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ID PMID Title PublicationDate abstract
22647860 Persistent periodontal disease hampers anti-tumor necrosis factor treatment response in rh 2012 Jun OBJECTIVE: This study aimed to evaluate prospectively the influence and the evolution of periodontal disease (PD) in rheumatoid arthritis (RA) patients submitted to anti-tumor necrosis factor (TNF) therapy. METHODS: Eighteen patients with RA (according to the American College of Rheumatology criteria) were assessed for PD before (BL) and after 6 months (6M) of anti-TNF treatment: 15 infliximab, 2 adalimumab, and 1 etanercept. Periodontal assessment included plaque and gingival bleeding indices, probing pocket depth, cementoenamel junction, and clinical attachment level. Rheumatologic evaluation was performed blinded to the dentist's assessment: demographic data, clinical manifestations, and disease activity (Disease Activity Score using 28 joints [DAS28], erythrocyte sedimentation rate [ESR], and C-reactive protein [CRP]). RESULTS: The median age and disease duration of patients with RA were 50 years (25-71 y) and 94% were female. Periodontal disease was diagnosed in 8 patients (44.4%). Comparing BL to 6M, periodontal parameters in the entire group remained stable (P > 0.05) throughout the study (plaque and gingival bleeding indices, probing pocket depth, cementoenamel junction, and clinical attachment level), whereas an improvement in most analyzed RA parameters was observed in the same period: DAS28 (5.5 vs. 3.9, P = 0.02), ESR (21 vs. 12.5 mm/first hour, P = 0.07), and CRP (7.8 vs. 2.8 mg/dL, P = 0.25). Further analysis revealed that this improvement was restricted to the group of patients without PD (DAS28 [5.5 vs. 3.6, P = 0.04], ESR [23.0 vs. 11.5 mm/first hour, P = 0.008], and CRP [7.4 vs. 2.1, P = 0.01]). In contrast, patients with PD had lack of response, with no significant differences in disease activity parameters between BL and 6M: DAS28 (5.2 vs. 4.4, P = 0.11), ESR (17.0 vs. 21.0, P = 0.56), and CRP (9.0 vs. 8.8, P = 0.55). CONCLUSIONS: This study supports the notion that PD may affect TNF blocker efficacy in patients with RA. The possibility that a sustained gingival inflammatory state may hamper treatment response in this disease has high clinical interest because this is a treatable condition.
22766432 Abatacept use in rheumatoid arthritis: evidence review and recommendations. 2013 Jan OBJECTIVE: To review the clinical evidence on abatacept and to formulate recommendations in order to clear up points related to its use in rheumatology. METHOD: An expert panel of rheumatologists objectively summarized the evidence on the mechanism of action, practicalities, effectiveness and safety of abatacept, and formulated recommendations following a literature review. The level of evidence and degree of recommendation was established. RESULTS: The document presents 21 statements focused on evidence or recommendations on abatacept (14 evidence summaries and 9 recommendations). The level of evidence was 2b or higher according to the Oxford Centre for Evidence-Based Medicine scale on 14 occasions. The degree of the recommendation was A in two recommendations, C in one, and D in the rest. It was considered important to make recommendations on aspects with lower levels of evidence. CONCLUSIONS: This is a practical document to supplement the summary of product characteristics.
23173263 [Effects of sinomenine and methotrexate on fibroblast-like synoviocytes in rheumatoid arth 2012 Aug OBJECTIVE: To investigate the effects of sinomenine (SIN) and methotrexate (MTX) on the proliferation and apoptosis of in vitro cultured fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) patients, as well as the expression of osteoclast differentiation factor in FLS. METHODS: FLS were isolated from the synovium of RA patients and cultured in vitro. FLS were incubated with different concentrations of SIN and MTX respectively or combined: 0.001, 0.010, 0.100, 1.000 mg/mL SIN; 0.001, 0.010, 0.100, 1.000 mg/mL MTX; 0.001 mg/mL SIN + 0.001 mg/mL MTX, 0.010 mg/mL SIN + 0.010 mg/mL MTX, 0.100 mg/mL SIN + 0.100 mg/mL MTX, 1.000 mg/mL SIN + 1.000 mg/mL MTX, namely SIN1, 2, 3, 4 groups; MTX1, 2, 3, 4 groups and the combination 1, 2, 3, 4 groups. The medium without drugs was used as a control group. There was a total of 13 groups, each group with 3 complex holes. MTT was applied to detect the growth of FLS. The flow cytometry was applied to detect the apoptosis of FLS. The expressions of FLS receptor activator of nuclear factor kappa B ligand (RANKL) mRNA and osteoprotegerin (OPG) mRNA were observed by semi-quantitative RT-PCR. RESULTS: Compared with the control group, RA FLS proliferation OD values of all the drug groups were lower (P < 0.05). The RA FLS apoptosis OD value of the combination 3 group increased, the OPG mRNA expression increased, the expression of RANKL mRNA decreased with statistical difference (P < 0.05). The RA proliferation OD values of the SIN3 group and the MTX3 group increased when compared with the combination 3 group (P < 0.05). CONCLUSIONS: SIN and MTX had synergistic effects in inhibiting FLS. This might be one of the mechanisms for inhibiting RA bone damage.
21789610 Th17 peripheral cells are increased in diffuse cutaneous systemic sclerosis compared with 2012 Sep Systemic Sclerosis (SSc) is an autoimmune disease characterized by fibrosis and vasculopathy. A key feature is the presence of T cells in inflammatory lesions. To establish the differences in peripheral blood T helper (Th) subpopulations in diffuse cutaneous (dc) and limited cutaneous (lc) SSc patients, blood samples from 57 dcSSc and 78 lcSSc patients were obtained. Controls were collected from healthy volunteers (n = 16), active systemic lupus erythematosus (aSLE) patients (n = 13), and active rheumatoid arthritis (aRA) patients (n = 12). Mononuclear cells were analyzed by flow cytometry to determine Th1 (CD4+/IFN-γ+), Th2 (CD4+/IL-4+), Th17 (CD4+/IL-17+), and regulatory T cells (Tregs; CD4+/CD25+/Foxp3+) subsets. Th17 and Th1 subsets were increased in SSc groups versus healthy controls (P < 0.001) and aSLE patients (P < 0.001 for Th17 and P < 0.008 for Th1). Th2 cells were higher in dcSSc patients than in the healthy and aSLE groups (P = 0.03 and P = 0.009, respectively). Tregs were increased in the aRA group when compared with SSc patients and healthy controls (P ≤ 0.003). Patients with immunosuppressive treatment had lower numbers of Th17 and Th2 cells (P = 0.02). Our results shed further light into the preponderant role of Th17 and Th1 in patients with SSc. However, these findings certainly deserve to be studied in depth.
21611196 miR-346 controls release of TNF-α protein and stability of its mRNA in rheumatoid arthrit 2011 TNF-α is a major cytokine implicated in rheumatoid arthritis. Its expression is regulated both at the transcriptional and posttranscriptional levels and recent data demonstrated that miRNAs are implicated in TNF-α response in macrophages. LPS-activated FLS isolated from RA patients express TNF-α mRNA but not the mature protein. This prompted us to look for miRNAs which could be implicated in this anti-inflammatory effect. Using a microarray, we found two miRNAs, miR-125b and miR-939 predicted to target the 3'-UTR of TNF-α mRNA, to be up-regulated in RA FLS in response to LPS, but their repression did not restore mature TNF-α expression in FLS. We showed previously that miR-346, which is upregulated in LPS-activated FLS, inhibited Btk expression that stabilized TNF-α mRNA. Blocking miR-346 reestablished TNF-α expression in activated FLS. Interestingly, transfection of miR-346 in LPS-activated THP-1 cells inhibited TNF-α secretion. We also demonstrated that TTP, a RNA binding protein which inhibited TNF-α synthesis, is overexpressed in activated FLS and that inhibition of miR-346 decreases its expression. Conversely, transfection of miR-346 in LPS-activated THP-1 cells increased TTP mRNA expression and inhibited TNF-α release. These results indicate that miR-346 controls TNF-α synthesis by regulating TTP expression.
22617075 [Malignancy risk during TNF-blocking therapy increased or not?]. 2012 Tumour necrosis factor α (TNF) blockers were a major step forward in the treatment of patients with rheumatoid arthritis. In view of their immunosuppressive effects, concerns about enhancement of cancer development have arisen. So far there is no firm evidence that TNF-blockers increase the risk of solid tumours or lymphomas. However, it appears likely that TNF-blockers enhance the risk of non-melanoma skin cancer in patients with RA. Hence, it is recommended to screen patients treated with TNF-blockers periodically for skin cancer whereas routine screening for other malignancies is not useful.
23104101 Seven sirtuins for seven deadly diseases of aging. 2013 Mar Sirtuins are a class of NAD(+)-dependent deacetylases having beneficial health effects. This extensive review describes the numerous intracellular actions of the seven mammalian sirtuins, their protein targets, intracellular localization, the pathways they modulate, and their role in common diseases of aging. Selective pharmacological targeting of sirtuins is of current interest in helping to alleviate global disease burden. Since all sirtuins are activated by NAD(+), strategies that boost NAD(+) in cells are of interest. While most is known about SIRT1, the functions of the six other sirtuins are now emerging. Best known is the involvement of sirtuins in helping cells adapt energy output to match energy requirements. SIRT1 and some of the other sirtuins enhance fat metabolism and modulate mitochondrial respiration to optimize energy harvesting. The AMP kinase/SIRT1-PGC-1α-PPAR axis and mitochondrial sirtuins appear pivotal to maintaining mitochondrial function. Downregulation with aging explains much of the pathophysiology that accumulates with aging. Posttranslational modifications of sirtuins and their substrates affect specificity. Although SIRT1 activation seems not to affect life span, activation of some of the other sirtuins might. Since sirtuins are crucial to pathways that counter the decline in health that accompanies aging, pharmacological agents that boost sirtuin activity have clinical potential in treatment of diabetes, cardiovascular disease, dementia, osteoporosis, arthritis, and other conditions. In cancer, however, SIRT1 inhibitors could have therapeutic value. Nutraceuticals such as resveratrol have a multiplicity of actions besides sirtuin activation. Their net health benefit and relative safety may have originated from the ability of animals to survive environmental changes by utilizing these stress resistance chemicals in the diet during evolution. Each sirtuin forms a key hub to the intracellular pathways affected.
22416455 [Rheumatic diseases and research on laboratory medicine: new applications of old knowledge 2012 Jan Although the etiology of rheumatic diseases has not been elucidated, it seems to be involved in excessive autoimmune responses. In 1976, we began to research rheumatic diseases, especially rheumatoid arthritis. Anti-human immunoglobulin allotype antibodies in Japanese sera were collected from blood donors or patients by hemagglutination and the hemagglutination inhibition method using anti-D sensitized erythrocytes. Many rheumatoid factors without any specificity to IgG allotypes (Gm allotypes) were detected in patient sera. On the other hand, so-called anti-antibodies, Andresen type but not Milgrom type, were mainly detected in blood donors. Thirty-nine sera possessing anti-Gm and anti-Km antibody specificities were finally obtained by screening about 80,000 Japanese. The antibody to G1m (f) was most frequently detected, but the antibody to G1m (z), which is an allele of G1m (f), was not obtained. Quantitative evaluation of rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) was adopted in the 2010 ACR/EULAR classification criteria for rheumatoid arthritis; however, quality management of RF has been incompletely implemented in Japan. We therefore mounted an effort to standardize the cutoff value. We found marked hyperferritinemia in patients with active adult Still's disease in 1987. Additionally, ratios of glycosylated ferritin in the patients were extremely reduced, even if they came into the inactive phase. This depressive production of glycosylated ferritin might be a marked characteristic of this disease. Finally, the development of musculoskeletal ultrasonography in rheumatic diseases is introduced.
22718923 Optimizing outcomes in patients with rheumatoid arthritis and an inadequate response to an 2012 Jul A failure to respond to TNF inhibitors remains a serious concern for patients with RA. Although some patients experience a primary lack of drug efficacy in reducing their symptoms, others fail to maintain an initial response because of acquired drug resistance. While switching to another TNF inhibitor is a common practice for patients who are not responsive to a particular treatment, limited clinical trial data support this strategy. If more than one TNF inhibitor provides inadequate responses and/or similar tolerability issues, switching to a different class of agent may provide a more effective option. Currently four non-TNF inhibitors are approved for use in RA patients-the T-cell co-stimulation inhibitor abatacept, the B-cell-depleting mAb rituximab, the IL-1 receptor blocker anakinra and the IL-6 receptor inhibitor tocilizumab. These biologic agents have been studied in large, randomized placebo-controlled trials that demonstrate their efficacy in reducing disease activity in patients failing TNF inhibitor therapy. Results with the majority of these agents suggest that their administration may provide a greater proportion of patients with an effective, evidence-based disease-modifying approach earlier in the course of their disease than switching TNF inhibitors.
21725663 [Littler tenodesis for correction of swan neck deformity in rheumatoid arthritis]. 2011 Jul OBJECTIVE: Correction of swan neck deformity at the PIP and DIP joint by reconstruction of the oblique retinacular ligament through palmar transposition of one distally pedicled lateral band (oblique retinacular ligament reconstruction (ORL) = Littler II). INDICATIONS: Rheumatoid swan neck deformity Nalebuff stages I-III (dynamic, partially contracted, contracted). The swan neck deformity should be of articular origin. CONTRAINDICATIONS: Advanced radiologic changes of the PIP joint (Larsen 3-4) [12]. Extrinsic and intrinsic causes of swan neck deformity. Flexor tendon synovitis. SURGICAL TECHNIQUE: Dorsal approach to the PIP joint. One lateral band is sectioned proximally at the level of the musculotendinous junction. It is then isolated from the extensor apparatus and left pedicled distal at the insertion. The isolated lateral band is then passed underneath the Cleland ligament from distal to proximal and is sutured to the distal edge of the A2 pulley. The correct tension of the tenodesis achieves flexion at the PIP joint and extension at the DIP joint. In contracted and partially contracted joints, the PIP joint is temporarily transfixed. Depending on the clinical findings, a synovectomy or dorsal arthrolysis of the PIP joint must be performed. POSTOPERATIVE MANAGEMENT: Immediate postoperative mobilization of the PIP joint for flexion. A figure-of-eight finger splint has to be worn for 12 weeks. The splint must allow full PIP flexion and limit extension over 20-30° of flexion. In case of temporary transfixation of the PIP joint, wire removal after 4-6 weeks and start of mobilization. Passive extension over 20-30° of flexion only after 12 weeks. RESULTS: From 2004-2007, 30 PIP joints in 20 rheumatoid patients were treated for swan neck deformity. In all cases, the original method as described by Littler was used. A change of the procedure due to insufficiency of the Cleland ligament or the A2 pulley was not necessary in any of the cases. After a mean of 22 months, 26 PIP joints in 17 patients could be followed up. In 12 PIP joints, the deformity was partially contracted, in two joints contracted. In 10 joints, a dorsal arthrolysis had to be performed, while a lengthening of the medial band was performed in 1 patient. The swan neck deformity could be compensated in all cases. Preoperative hyperextension of a mean 21° could be reduced to a mean 24° of flexion postoperatively. The ROM did not change much but was shifted from the extension sector to the flexion sector of the PIP joint. In no case were complications or recurrence of the deformity noted. Pain could be reduced in all patients except one. The radiologic joint situation was Larsen stage 2.2 preoperatively and 2.3 postoperatively.
22556134 Anxiety and depressive symptoms and illness perceptions in psoriatic arthritis and associa 2012 Oct OBJECTIVE: Symptoms of psychological distress, including anxiety and depressive symptoms, and illness perceptions are important in determining outcome in patients with rheumatic disease. We aimed to compare psychological distress in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) and to test whether the association between psychological variables and health-related quality of life (HRQOL) was similar in the 2 forms of arthritis. METHODS: In 83 PsA patients and 199 RA patients, we used the Patient Health Questionnaire 9 (PHQ-9), the Symptom Checklist-90-Revised, and the Brief Illness Perception Questionnaire to assess psychological variables and the World Health Organization Quality of Life Instrument, Short Form to assess HRQOL. We used hierarchical regression analysis to determine the associations between psychological variables and HRQOL after adjusting for demographic variables and disease parameters. RESULTS: The prevalence of moderate to severe levels of depressive symptoms (PHQ-9 score ≥10) was 21.7% in PsA patients, 25.1% in RA patients, and 36.7% in those PsA patients with polyarthritis. After adjustment for severity of disease and pain, anxiety (β = -0.28) and concern about bodily symptoms attributed to the illness (β = -0.33) were independent correlates of physical HRQOL in PsA. In RA, depressive symptoms (β = -0.29) and concern about the consequences of the arthritis (β = -0.27) were independent correlates of physical HRQOL. CONCLUSION: These findings suggest strongly that psychological factors are important correlates of HRQOL in PsA as well as in RA. Attention to patients' anxiety and their concern about numerous bodily symptoms attributed to the illness may enable rheumatologists to identify and manage treatable aspects of HRQOL in PsA.
22966146 Clinical evaluation of the efficacy of the P2X7 purinergic receptor antagonist AZD9056 on 2012 Oct OBJECTIVES: The P2X(7) purinergic receptor antagonist AZD9056 was evaluated in a phase IIa study and subsequently in a phase IIb study to assess the effects of orally administered AZD9056 on the signs/symptoms of rheumatoid arthritis (RA), with American College of Rheumatology 20% response criteria (ACR20) as the primary outcome. METHODS: Both studies were randomised, double-blind, placebo-controlled, parallel-group studies in patients with RA receiving methotrexate or sulphasalazine. Phase IIa was an ascending-dose trial in two cohorts (n=75) using AZD9056 administered daily over 4 weeks. Phase IIb included an open-label etanercept treatment group. Patients were randomised to receive treatment for 6 months with 50, 100, 200 or 400 mg AZD9056 (oral, once a day) or matching placebo (oral, once a day), or subcutaneous etanercept (50 mg once a week). RESULTS: In phase IIa, 65% of AZD9056 recipients at 400 mg/day responded at the ACR20 level compared with 27% of placebo-treated patients. A significant reduction in swollen and tender joint count was observed in the actively treated group compared with placebo, whereas no effect on acute-phase response was observed. Of 385 randomised patients in the phase IIb study, 383 received treatment. AZD9056 (all doses) had no clinically or statistically significant effect on RA relative to placebo as measured by the proportion of patients meeting the ACR20 criteria at 6 months and further supported by secondary end points. In both studies AZD9056 was well tolerated up to 400 mg/day. CONCLUSIONS: AZD9056 does not have significant efficacy in the treatment of RA, and the P2X(7) receptor does not appear to be a therapeutically useful target in RA. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00520572.
20959150 The increased in vitro osteoclastogenesis in patients with rheumatoid arthritis is due to 2011 Mar 1 Increases in local and systemic bone resorption are hallmarks of rheumatoid arthritis (RA). Osteoclasts are implicated in these processes and their enhanced differentiation may contribute to bone destruction. We observed that in vitro osteoclastogenesis varies among healthy individuals and hypothesized that increased osteoclastogenesis could be a marker for the presence of RA. Our objective in the present study was to determine if in vitro osteoclastogenesis from peripheral blood mononuclear cells (PBMCs) was different in patients with RA compared to healthy controls and osteoarthritis (OA) patients. Expression of CD14 in PBMCs was quantified and PBMCs were incubated for 21 days in the presence of the osteoclastogenic cytokines M-CSF and RANKL. Differentiation on cortical bone slices permitted the analysis of bone resorption while apoptotic potential was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. In vitro osteoclastogenesis was higher in PBMCs from RA patients compared to controls, and a similar increase was observed in the percentage of osteoclast precursors in RA patients. Osteoclasts from RA patients showed lower apoptotic rates than osteoclasts from healthy controls. No difference was observed in bone resorption activity between RA patients and controls. Interestingly, the difference in osteoclast number and apoptosis rate allowed the implementation of an algorithm capable of distinguishing patients with RA from controls. In conclusion, our study shows that osteoclast differentiation from PBMCs is enhanced in patients with RA, and this difference can be explained by both a higher percentage of osteoclast precursors in the blood and by the reduced apoptotic potential of mature osteoclasts.
20738421 Varying expression of four genes sharing a common regulatory sequence may differentiate rh 2011 Jan The CD28 gene is similarly down-regulated in CD4(+) lymphocytes from both healthy elderly people and patients with rheumatoid arthritis (RA) because of impaired protein-binding activity of the 'α' sequence in its promoter region. Other genes important for the CD4(+) cell function may share that sequence and may be similarly regulated and affected. We searched GenBank for possible 'α' homologues and then compared transcriptional activities of the respective genes in the CD4(+) cells of young and older healthy individuals and those with RA by real-time PCR. We show here that genes encoding one of the zinc finger proteins (ZNF334), the 'aging hormone' Klotho, the retinoid acid receptor β2 (RARβ2) and the T-cell adapter protein GRAP-2, contain sequences with various (exceeding 70%) degrees of homology to the 'α' sequence near their promoters. These genes are transcribed in human CD4(+) lymphocytes; the expressions of RARβ2, KLOTHO and ZNF334 are significantly decreased in a correlated manner in the cells of patients with RA compared with those of healthy individuals. In RA patients, the extremely reduced expression of ZNF334 does not depend on the individual's age, apparently constituting a disease-related phenomenon; whereas that of RARβ2 and KLOTHO occurs mostly in the cells of relatively younger patients, making them similar to the lymphocytes of healthy elderly in this aspect.
23229722 Oral antigens induce rheumatoid arthritis-like inflammation in a rat model. 2013 Mar BACKGROUND AND AIMS: The pathogenesis of rheumatoid arthritis (RA) is to be further elucidated. The present study aims to investigate the role of oral antigen in the induction of RA-like inflammation in the articular joints of rats. METHODS: An RA animal model was developed by gavage-feeding with antigen and aspirin, and lipopolysaccharide intraperitoneal injection. The gut epithelial barrier function was assessed by the absorption of mannitol and lactose. The absorption of the specific antigen was observed by the immune fluorescent method. The frequency of antigen specific CD4+ T cells in the peripheral system was assessed by flow cytometry. The inflammation in the ankle joints was evaluated by light microscopy and immunohistochemistry. RESULTS: Rats treated with aspirin showed intestinal barrier dysfunction; high contents of the specific antigen were absorbed into the lamina propria. The antigen specific CD4+ T cells were detected in the spleen that could be activated by exposure to the specific antigen as well as the extracts of joint tissue. High levels of proinflammatory cytokines were detected in the sera. Antigen specific immune complexes were localized in the ankle joints. Heavy extravasation was observed in the synovial cavity. The histology showed an inflammatory feature in the ankle joints. CONCLUSIONS: Oral antigen can induce RA-like inflammation in the articular joints under certain environment such as gut epithelial barrier dysfunction.
21400475 The anti-CD20 antibody rituximab reduces the Th17 cell response. 2011 Jun OBJECTIVE: Rituximab has been shown to be successful in the treatment of rheumatoid arthritis (RA), and this unexpected finding indicates that B cells have an important role in this disease. The present study was undertaken to investigate the mechanism of action of rituximab in RA. METHODS: Twelve patients with active RA were treated with rituximab. Disease activity was evaluated using the 28-joint Disease Activity Score. Synovial biopsy samples obtained at baseline and 12 weeks after treatment initiation were analyzed by microarray, quantitative polymerase chain reaction, and immunohistochemistry. Peripheral blood mononuclear cells (PBMCs) from healthy volunteers and from 4 patients with X-linked agammaglobulinemia were stimulated with the Th17-inducing stimulus Candida albicans, and the response in the presence and absence of rituximab was examined. RESULTS: In RA patients, rituximab reduced expression of retinoic acid-related orphan receptor γt and interleukin-22 (IL-22) and numbers of Th17-positive cells in synovial tissue, and this correlated with better clinical outcome. Rituximab did not affect tumor necrosis factor α (TNFα), Th1 cell, or Treg cell responses. Rituximab strongly reduced in vitro IL-17 and IL-22 production induced by C albicans. This effect was not observed in PBMCs from patients with X-linked agammaglobulinemia. CONCLUSION: Rituximab reduced the local Th17 response in RA patients, whereas it did not influence Th1 cell, Treg cell, or TNFα responses. The decreased Th17 response was associated with reduced inflammation and better clinical outcome. Moreover, inhibition of the Th17 response by rituximab was lost in the absence of B cells, providing evidence that the effects of rituximab are due to B cell depletion. These data demonstrate an unexpected role of B cells in the development of Th17 responses, which could possibly lead to B cell-based strategies for the treatment of Th17-related autoimmune diseases.
22012755 [Musculoskeletal ultrasound II - «why are bats better than physicians»]. 2011 Oct 19 This article reviews the aspects which were discussed at the SGUM congress in Davos in the talk «why are bats better than physicians». The talk focussed on modern aspects of Ultrasound (US) diagnostics at the locomotor system. High frequency US probes allow accurate diagnosis, initial assessment and follow up in Rheumatoid Arthritis and Osteo-Arthritis. Basic pathologic features in these pathologic conditions in form of synovitis, erosion and cartilage damage are described. In case of entrapment neuropathies - first of all in carpal tunnel syndrome - pathognomonic sonomorphologic changes can be detected and allow to confirm a clinical suspicion. The correct indication for diagnostic or therapeutic interventions at the musculoskeletal system can be critically verified and if necessary revised. The guidance of the intervention by US guarantees high accuracy of needle placement and thereby increases the diagnostic yield and the therapeutic success of injections/infiltrations.
22129077 The fine specificity of IgM anti-citrullinated protein antibodies (ACPA) is different from 2011 INTRODUCTION: The antigen recognition pattern of immunoglobulin M (IgM) could, when directed against protein antigens, provide an indication of the antigenic moieties triggering new B cells. The half-life of IgM is short and memory B cells against T-cell-dependent protein antigens typically produce IgG and not IgM antibodies. In this study, we analyzed whether a difference exists between the fine specificity of IgM versus IgG anti-citrullinated protein antibodies (ACPAs). METHODS: We determined the fine specificity of IgM and IgG ACPAs in 113 ACPA-positive rheumatoid arthritis patients with IgM cyclic citrullinated peptide 2 (CCP2) levels above 100 AU/ml. Fine specificity was assessed by performing ELISA using citrullinated peptides derived from vimentin, fibrinogen-β, fibrinogen-α and α-enolase, as well as citrullinated proteins fibrinogen and myelin basic protein. The arginine counterparts were used as controls. RESULTS: Recognition of defined citrullinated antigens by IgM ACPA was confined to samples that also displayed recognition by IgG ACPA. However, the IgM ACPA response displayed a more restricted antigen recognition profile than IgG ACPA (OR = 0.26, P < 0.0001). CONCLUSION: Our data show that several defined citrullinated antigens are recognized only by IgG ACPA, whereas others are also recognized by IgM ACPA. These observations suggest that not all citrullinated antigens are able to activate new B cells despite concurrent recognition by IgG ACPA.
22508468 A randomized comparative effectiveness study of oral triple therapy versus etanercept plus 2012 Sep OBJECTIVE: To assess whether it is better to intensively treat all patients with early rheumatoid arthritis (RA) using combinations of drugs or to reserve this approach for patients who do not have an appropriate response (as determined by a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate [DAS28-ESR] of ≥ 3.2 at week 24) to methotrexate (MTX) monotherapy, and to assess whether combination therapy with MTX plus etanercept is superior to the combination of MTX plus sulfasalazine plus hydroxychloroquine. METHODS: The Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) study is a 2-year, randomized, double-blind trial. A 2 × 2 factorial design was used to randomly assign subjects to 1 of 4 treatment arms: immediate treatment with MTX plus etanercept, immediate oral triple therapy (MTX plus sulfasalazine plus hydroxychloroquine), or step-up from MTX monotherapy to one of the combination therapies (MTX plus etanercept or MTX plus sulfasalazine plus hydroxychloroquine) at week 24 if the DAS28-ESR was ≥ 3.2. All treatment arms included matching placebos. The primary outcome was an observed-group analysis of DAS28-ESR values from week 48 to week 102. RESULTS: At week 24 (beginning of the step-up period), subjects in the 2 immediate-treatment groups demonstrated a greater reduction in the DAS28-ESR compared with those in the 2 step-up groups (3.6 versus 4.2; P < 0.0001); no differences between the combination-therapy regimens were observed. Between week 48 and week 102, subjects randomized to the step-up arms had a DAS28-ESR clinical response that was not different from that of subjects who initially received combination therapy, regardless of the treatment arm. There was no significant difference in the DAS28-ESR between subjects randomized to oral triple therapy and those randomized to receive MTX plus etanercept. By week 102, there was a statistically significant difference in the change in radiographic measurements from baseline between the group receiving MTX plus etanercept and the group receiving oral triple therapy (0.64 versus 1.69; P = 0.047). CONCLUSION: There were no differences in the mean DAS28-ESR during weeks 48-102 between subjects randomized to receive MTX plus etanercept and those randomized to triple therapy, regardless of whether they received immediate combination treatment or step-up from MTX monotherapy. At 102 weeks, immediate combination treatment with either strategy was more effective than MTX monotherapy prior to the initiation of step-up therapy. Initial use of MTX monotherapy with the addition of sulfasalazine plus hydroxychloroquine (or etanercept, if necessary, after 6 months) is a reasonable therapeutic strategy for patients with early RA. Treatment with the combination of MTX plus etanercept resulted in a statistically significant radiographic benefit compared with oral triple therapy.
22847679 Worst-case future scenarios of patients with rheumatoid arthritis: a cross-sectional study 2012 Nov OBJECTIVE: The time trade-off is a health-related quality of life instrument that measures valuations for health states (utilities) by asking patients to value their health state anchored on a scale between death (0) and perfect health (1). Dying earlier is not perceived as a realistic worst-case consequence of the disease by RA patients. Of the previous focus groups study on RA patients, five worst-case future scenarios emerged. The aim of this study was to examine which potential worst-case scenario was the most appropriate for RA patients to use in utility calculation. METHODS: In a cross-sectional study of 74 consecutive RA patients visiting the rheumatology outpatient clinic, participants were presented with descriptions of the five worst-case future scenarios. In pairwise comparisons, patients had to choose the scenario that would be the worst to experience. The worst-case future scenario was defined by the scenario that was chosen by a significantly greater proportion of participants than could be expected based on chance (20%). Therefore, analysis based on a single fraction ( ) was used and 95% CI was calculated. RESULTS: The scenario being dependent on others was chosen most often as the worst to experience [by 35% of participants (95% CI 24%, 46%)] and significantly more often than could be expected based on chance (  = 0.35, z = 6.45, P = 0.00). CONCLUSION: The scenario being dependent on others is likely to be the most appropriate worst-case future scenario for RA patients. Using an alternative anchor could improve the validity and responsiveness of the time trade-off in RA patients.