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ID PMID Title PublicationDate abstract
17982455 Rheumatoid arthritis association at 6q23. 2007 Dec The Wellcome Trust Case Control Consortium (WTCCC) identified nine single SNPs putatively associated with rheumatoid arthritis at P = 1 x 10(-5) - 5 x 10(-7) in a genome-wide association screen. One, rs6920220, was unequivocally replicated (trend P = 1.1 x 10(-8)) in a validation study, as described here. This SNP maps to 6q23, between the genes oligodendrocyte lineage transcription factor 3 (OLIG3) and tumor necrosis factor-alpha-induced protein 3 (TNFAIP3).
18592145 Profile of exoglycosidases in synovial cell cultures derived from human synovial membrane. 2008 OBJECTIVE: Determining the activity of lysosomal exoglycosidases in tissue cultures of synoviocytes derived from the knee joints of patients with injured anterior cruciate ligaments (ACL), juvenile idiopathic arthritis (JIA), and rheumatoid arthritis (RA). METHODS: The following exoglycosidases in cultured synoviocytes were analyzed with p-nitrophenyl derivatives of appropriate sugars as substrates: hexosaminidase (HEX) and its isoenzyme A (HEX-A), beta-glucuronidase (GluA), beta-galactosidase (GAL), alpha-mannosidase (MAN), and alpha-fucosidase (FUC). RESULTS: In our cell cultures, fibroblast-like synovial cells (FLS) dominated. In the group of patients with ACL-injuries, and in the groups of patients with JIA and RA, the activity of the investigated exoglycosidases was significantly higher in the intra- rather than in the extracellular compartment. Hexosaminidase was the predominant exoglycosidase. Stimulation of synoviocytes by IL-1beta in cell cultures significantly increased the activity of HEX, HEX-A, and GluA in both compartments, as well as of GAL, MAN, and FUC in the intracellular compartment. Stimulation by IL-1beta rheumatoidal synoviocytes increased by 128-201% the activity of HEX and HEX A in intracellular compartments and 33-72% in extracellular compartment. CONCLUSIONS: The profile of lysosomal exoglycosidases in a cell culture of human synoviocytes is similar, but not identical, to those in the knee joint. Hexosaminidase is the dominant glycosidase in cultured unstimulated and IL-1beta-stimulated human synoviocytes. The HEX inhibitors may be new drugs for the treatment of inflamed knee joints.
16861707 Increased expression of CD154 (CD40L) on stimulated T-cells from patients with psoriatic a 2007 Feb OBJECTIVES: CD40L is a costimulatory molecule and an early activation marker of T-lymphocytes. Based on the hypothesis that activated T-cells may play a role in the pathogenesis of psoriatic arthritis (PsA), we evaluated the level of CD40L expression on T-cells from patients with PsA. METHODS: We analysed 12 patients with PsA, six patients with rheumatoid arthritis (RA) and four healthy volunteers. T-cell surface expression of CD40L was evaluated using two-colour flow cytometry in (i) the resting state and (ii) following stimulation with phorbol myristate acetate/ionomycin, with or without ciclosporin (CsA)-mediated inhibition. RESULTS: Expression of CD40L was significantly increased on activated T-cells from patients with PsA, particularly those with active disease, when compared with normal individuals and patients with RA (mean percentages of CD3+ CD40L+ cells: 23.74, 11.59 and 9.57% for patients with active PsA, patients with RA and healthy volunteers, respectively). CsA-mediated inhibition of CD40L induction was equally effective in all study groups. CONCLUSION: CD40L is overexpressed on T-cells from patients with active PsA. This may indicate a role for CD40L in PsA pathogenesis. Larger-scale studies are warranted to address these issues.
20306675 Pro-inflammatory and anti-inflammatory cytokines profile in rheumatoid arthritis patients. 2008 Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by severe joint deformities due to bony erosions and tendon damage. Cytokines are protein mediators of inflammation and are produced as a result of the activation of various cellular reactions. They are the final mediators and/or regulators of the inflammatory process. Cytokines such as TNF-alpha and IL-6, play key roles in driving the inflammation and synovial cell proliferation that characterize rheumatoid arthritis and joint destruction. Sera from 58 RA patients were analyzed for TNF-alpha, IL-6, IL-10, TGF-beta, sTNF-R 1 and sTNF-R2 using ELISA. The proinflammatory cytokines TNF-alpha and IL-6 were significantly elevated in RA patients, while TGF-beta, an immunomodulatory cytokine, was elevated in control individuals. Assays of TNF receptors, sTNF-R1 and sTNF-R2, were noted to be significantly elevated in RA patients when compared to control. Our data indicate that local production of cytokine inhibitors is capable of diminishing cytokine and disease activity thereby may improve signs, symptoms and quality of life for patients with RA.
18815004 Illness perceptions in patients with fibromyalgia. 2009 Jan OBJECTIVE: Former studies in chronic diseases showed the importance of patients' beliefs and perceptions. The Revised Illness Perception Questionnaire was developed to assess these illness perceptions. Our goal was to investigate psychometric properties of the IPQ-R for Fibromyalgia Dutch language version (IPQ-R FM-Dlv) and to describe illness perceptions of participants with FM. METHODS: 196 patients completed the IPQ-R FM-Dlv. Internal consistency, domain structure and inter domain correlations were calculated and compared to the IPQ-R English language version. Scores were compared with chronic fatigue syndrome (CFS), rheumatoid arthritis (RA), and coronary heart disease (CHD). RESULTS: Most psychometric properties were comparable to those of the original IPQ-R. Participants showed a lack of understanding of their illness, expected their FM to be chronic and to have a lot of negative consequences on functioning. In 17 out of 24 domains significant differences were found between FM and CFS, RA, and CHD patients. CONCLUSION: The IPQ-R FM-Dlv showed acceptable psychometric properties, although some aspects need closer examination. Illness perceptions of FM patients on the Dutch questionnaire were non-comparable to CFS, RA, and CHD patients on the English questionnaire. PRACTICE IMPLICATIONS: The IPQ-R FM-Dlv can be used to assess illness perceptions of Dutch FM patients.
18061654 Adiponectin and inflammation: consensus and controversy. 2008 Feb Circulating levels of adiponectin decrease with increasing visceral obesity and are lower in patients with type 2 diabetes, the metabolic syndrome, and cardiovascular disease compared with controls matched by body mass index. Several reports demonstrated anti-inflammatory effects of adiponectin. Because increased adipose tissue is associated with low-grade chronic inflammation and proinflammatory factors inhibit adiponectin production, the current hypothesis states that chronic inflammation associated with visceral obesity inhibits production of adiponectin, perpetuating inflammation. The negative correlation between adiponectin and markers of inflammation in the aforementioned conditions supports this hypothesis. In contrast with disorders typically associated with excess adiposity and positive energy balance, adiponectin levels are elevated--rather than decreased--in classic chronic inflammatory/autoimmune diseases that are unrelated to increased adipose tissue, such as rheumatoid arthritis, SLE, inflammatory bowel disease, type 1 diabetes, and cystic fibrosis. In these patients, adiponectin levels positively--rather than negatively--correlate with inflammatory markers. Furthermore, proinflammatory effects of adiponectin have been reported in tissues such as joint synovium and colonic epithelium. Thus, adiponectin is regulated in the opposite direction and may exert differential functions in classic versus obesity-associated inflammatory conditions. This article discusses this apparent paradox and presents possible alternative and/or complementary explanations.
17369033 Induced sputum as a tool for early detection of airway inflammation in connective diseases 2007 Jul BACKGROUND: Induced sputum (IS) sampling is a safe and validated approach to study bronchial inflammation in chronic obstructive lung diseases. Although promising results have also been reported in various diffuse interstitial lung disorders, the potential use of IS in the assessment of connective tissue diseases (CTD)-related lung involvement has not yet been investigated. AIM OF THE STUDY: To evaluate the clinical usefulness of IS in the early management of patients suffering from rheumatoid arthritis (RA) and systemic sclerosis (SSc) at the onset of respiratory symptoms. PATIENTS AND METHODS: The study population included 19 patients (RA=12; SSc=7) and 14 age- and sex-matched healthy volunteers. Lung function testing, high resolution computed tomography (HRCT) of the thorax and IS collection were performed in all cases. Broncho-alveolar lavage (BAL) was obtained in selected patients. RESULTS: IS samples from patients contained a significantly higher percentage of neutrophils and a lower percentage of macrophages compared to healthy subjects (p=0.002 and 0.001, respectively), while the total cell number showed no differences. In addition, sputa yielded both higher cell counts and higher neutrophils than BAL samples (p=0.02 in all instances). No correlations were found between IS findings and lung function parameters, HRCT and BAL findings. CONCLUSIONS: This is the first study investigating the inflammatory cell pattern in IS from CTD patients with early clinical evidence of lung involvement. Future studies are needed to determine whether the assessment of airway inflammation adds significant information that may result in a relevant improvement of disease management.
17111929 [The role of regulatory T-cells in autoimmune rheumatic diseases]. 2006 Regulatory T-cells CD4+CD25+Foxp3, possessing suppressory activity, play the key role in the development of autoimmune diseases, maintenance of peripheral tolerance in transplantation immunity, and the prevention of a pathological immune response to intestinal microflora or microbial infection. A decrease in the total number of circulating CD4+CD25+ regulatory T-cells and their suppressive activity have been found in patients suffering from various autoimmune diseases, such as type 1 diabetes, multiple sclerosis, autoimmune hepatitis, psoriatic arthritis, juvenile idiopathic arthritis, and systemic lupus erythematosus (SLE). The authors of this study investigated the phenotypic characteristics of peripheral blood lymphocytes in 31 SLE patients and the effect of treatment on the content of CD4+CD25+ T-cells before and after pulse therapy with methylprednisolone and cyclophosphan. The total number of regulatory T-cells in the group of untreated patients was almost twice lower vs. the group of healthy donors. As a result of the therapy, the proportion of regulatory T-cells increased significantly, although it did not reach the values in the control group. The data from this research confirm the development of a defect of CD4+CD25+ T-cells at the active phase of SLE, and a possibility to partially correct this defect with an effective therapy.
17391602 Purulent pericarditis in a patient with rheumatoid arthritis treated with etanercept and m 2007 Jan Purulent pericarditis is rarely seen in this post-antibiotic era. We report a case of spontaneous purulent pericarditis in a patient with rheumatoid arthritis being treated with etanercept, a tumour necrosis factor-alpha (TNF-alpha) antagonist, and methotrexate, an immunosuppressant. Both are disease-modifying anti-rheumatic drugs. We discuss the pathophysiology of purulent pericarditis and the recent literature on the infectious complications of TNF-alpha antagonists.
17884817 Hypoxia-inducible factor mediates hypoxic and tumor necrosis factor alpha-induced increase 2007 Nov 16 Chronic hypoxia and inflammatory cytokines are hallmarks of inflammatory joint diseases like rheumatoid arthritis (RA), suggesting a link between this microenvironment and central pathological events. Because TACE/ADAM17 is the predominant protease catalyzing the release of tumor necrosis factor alpha (TNFalpha), a cytokine that triggers a cascade of events leading to RA, we examined the regulation of this metalloprotease in response to hypoxia and TNFalpha itself. We report that low oxygen concentrations and TNFalpha enhance TACE mRNA levels in synovial cells through direct binding of hypoxia-inducible factor-1 (HIF-1) to the 5' promoter region. This is associated with elevated TACE activity as shown by the increase in TNFalpha shedding rate. By the use of HIF-1-deficient cells and by obliterating NF-kappaB activation, it was determined that the hypoxic TACE response is mediated by HIF-1 signaling, whereas the regulation by TNFalpha also requires NF-kappaB activation. As a support for the in vivo relevance of the HIF-1 axis for TACE regulation, immunohistological analysis of TACE and HIF-1 expression in RA synovium indicates that TACE is up-regulated in both fibroblast- and macrophage-like synovial cells where it localizes with elevated expression of both HIF-1 and TNFalpha. These findings suggest a mechanism by which TACE is increased in RA-affected joints. They also provide novel mechanistic clues on the influence of the hypoxic and inflammatory microenvironment on joint diseases.
16735693 Differential regulation of chemokine production by Fcgamma receptor engagement in human mo 2006 Aug CC chemokine ligand 1 (CCL1; I-309) is a CC chemokine that interacts with CC chemokine receptor 8, which is preferentially expressed in polarized T helper cell type 2 and Tc2 cells, in eosinophils, and in T regulatory cells. The present study, prompted by transcriptional profiling of human monocytes undergoing different forms of activation, was designed to characterize the production of CCL1 in monocytes compared with the production of other chemokines (CCL2, CCL22, and CCL18) differentially regulated by distinct activation signals. Lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), interleukin (IL)-1beta, tumor necrosis factor alpha, IL-4, IL-13, IL-10, IL-6, IL-18, and combinations thereof did not induce CCL1 production in monocytes, and some of these signals stimulated production of reference chemokines. Induction of CCL1 in monocytes required engagement of Fc receptor for immunoglobulin G (FcgammaR)II and exposure to IL-1beta or LPS. This combination of stimuli results in a form of M2 (M2b, Type 2) macrophage activation. FcgammaR engagement also induced CCL22 and amplified its stimulation by IL-4. In contrast, FcgammaR stimulation inhibited the IL-10- and LPS-mediated induction of CCL18. IL-10, IL-4, and IFN-gamma inhibited induction of CCL1 by FcgammaR ligation and IL-1beta. CCL1 was present in synovial fluids and macrophages in juvenile idiopathic arthritis. Thus, regulation of CCL1 in human monocytes is unique, with an obligate requirement of FcgammaR engagement and costimulation by signals (IL-1beta and LPS), which use the myeloid differentiation primary-response protein 88 adaptor protein. Thus, CCL1 is a CC chemokine with a unique pattern of regulation associated with a distinct form of M2 (Type 2, M2b) monocyte activation, which participates in macrophage-dependent regulatory circuits of innate and adaptive immunity.
18260178 Osteoclast inhibitory effects of vitamin K2 alone or in combination with etidronate or ris 2008 Mar OBJECTIVE: To investigate the effects of vitamin K2 (Vit K2) alone or in combination with etidronate and risedronate on bone loss, osteoclast induction, and inflammation in patients with rheumatoid arthritis (RA). METHODS: Subjects comprised 79 patients with RA who were receiving prednisolone, divided into 3 groups: Group K, Vit K2 alone; Group KE, Vit K2 plus etidronate; and Group KR, Vit K2 plus risedronate. During a 24-month treatment and followup period, levels of N-terminal telopeptide of type I collagen (NTx) and bone alkaline phosphatase were measured. Bone mineral density (BMD) of the 3 groups was measured using dual-energy x-ray absorptiometry. Damage score to fingers on radiographic findings were measured according to the Larsen method. Serum levels of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) were measured. RESULTS: Falls in rate of change of BMD decreased after 18 months in groups KR and KE. Larsen damage scores indicated a significant difference between Group KE and other groups. Significant decreases in serum NTx were observed in groups KE and KR at all timepoints, but not in Group K. Levels of RANKL decreased significantly in all 3 groups. CONCLUSION: Vit K2 alone or in combination with bisphosphonates for treatment of osteoporosis in patients with RA may inhibit osteoclast induction via decreases in levels of RANKL.
17726036 The expression of SOCS is altered in rheumatoid arthritis. 2007 Oct OBJECTIVES: Cytokines play a key pathogenic role in rheumatoid arthritis (RA). Several cytokines signal through the JAK-STAT pathway, which is negatively regulated by the suppressors of cytokine signalling (SOCS) proteins. Since SOCS protein levels can profoundly modulate cellular responses to cytokines, we have investigated their expression in chronic RA. METHODS: The levels of SOCS1-3 and CIS1 mRNA in peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MCs), purified T cells and monocytes from RA patients and healthy volunteers were studied using quantitative reverse transcriptase polymerase chain reaction (RT-PCR). SOCS mRNA and protein expression in synovial tissues were examined by RT-PCR and immunohistochemistry. RESULTS: The levels of SOCS1 and SOCS3 were significantly increased in PBMCs from RA patients when compared with healthy volunteers. These differences were mainly due to up-regulation of SOCS1 in PB T cells and of SOCS3 in PB monocytes. In addition, SOCS2 was up-regulated in PB T cells. Interestingly, SF T cells expressed lower and SF macrophages higher levels of SOCS molecules than their PB counterparts. Similarly, while a significant portion of macrophages in synovial tissues expressed SOCS1 and SOCS3 proteins, the majority of T cells remained SOCS negative. Finally, SOCS1 was up-regulated in the synovial membranes from patients with RA when compared with osteoarthritis. CONCLUSIONS: SOCS expression levels are profoundly altered in RA, and the profile of SOCS expression is dependent on both the cell type as well as the cellular compartment.
18852199 Autoimmune diseases: insights from genome-wide association studies. 2008 Oct 15 Autoimmune diseases occur when an individual's own immune system attacks and destroys his or her healthy cells and tissues. Although it is clear that environmental stimuli can predispose someone to develop autoimmune diseases, twin- and family-based studies have shown that genetic factors also play an important role in modifying disease risk. Because many of these diseases are relatively common (prevalence in European-derived populations: 0.01-1%) and exhibit a complex mode of inheritance, many DNA sequence variants with modest effect on disease risk contribute to the genetic burden. Recently, the completion of the HapMap project, together with the development of new genotyping technologies, has given human geneticists the tools necessary to comprehensively, and in an unbiased manner, search our genome for DNA polymorphisms associated with many autoimmune diseases. Here we review recent progress made in the identification of genetic risk factors for celiac disease, Crohn's disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and type-1 diabetes using genome-wide association studies (GWAS). Strikingly, GWAS have increased the number of genetic risk variants associated with these autoimmune diseases from 15 before 2006 to 68 now. We summarize what this new genetic landscape teaches us in terms of the pathogenesis of these diseases, and highlight some of the outstanding challenges ahead. Finally, we open a discussion on ways to best maximize the impact of these genetic discoveries where it matters the most, that is for autoimmune disease patients.
18390581 Rituximab use in everyday clinical practice as a first-line biologic therapy for the treat 2008 Jun OBJECTIVES: This study assessed the utility of rituximab for the therapy of RA in a non-academic environment in a group of cases where anti-TNF was either not available or relatively contraindicated. METHODS: Thirty-nine patients with active RA who had failed at least one DMARD received two rituximab infusions 2 weeks apart. Seventeen patients received two 1000 mg doses, and 22 received the 500 mg regimen. The 28-joint disease activity index (DAS28) and European League against Rheumatism (EULAR) response criteria were recorded at baseline, 3, 6, 9 and 12 months. RF and ANA were recorded at baseline and at 6 and 12 months. RESULTS: There was a significant improvement in the DAS28 at all time points, and EULAR response was observed in 29 of 33 patients (87.9%) at 3 months, 25 of 33 patients (75.8%) at 6 months, 22 of 29 patients (75.9%) at 9 months and 23 of 30 patients (76.7) at 12 months. Improvement was also noted in CRP, and both RF and ANA were generally reduced after treatment. Patients who were on the higher regimen of two 1000 mg doses appeared to respond slightly better compared with the lower dose regimen. CONCLUSIONS: Rituximab is well tolerated in everyday clinical practice and may represent a good short-term treatment option where anti-TNF therapy is either unavailable or relatively contraindicated.
19006766 Functional outcomes after arthroplasty of the distal radioulnar joint and hand therapy: a 2008 Oct The purpose was to present a therapy protocol for use after implantation of an ulnar head endoprosthesis and to describe the functional outcomes after hand therapy. This is a retrospective review of a series of eight patients treated with a specified therapy protocol after ulnar head resection and implant arthroplasty. Marked improvements in pain and function were reported, though some pain with exertion remained. Two patients were on worker's compensation and both have returned to their premorbid work status. Functional use of the extremity was achieved by two to six weeks, with a mean of four weeks. Maximum medical improvement with good-to-excellent early results was achieved in all patients by 16 weeks. It is our experience that with this directed therapy protocol patients undergoing this procedure experience rapid recovery and an ability to return to activities of daily living in a timely manner. This paper provides a baseline protocol and rationale for use with patients who have undergone surgery with an ulnar head endoprosthesis.
17324682 The association of depression and neuroticism with pain reports: a comparison of momentary 2007 Mar OBJECTIVE: Pain assessment has been shown to be affected by depression, neuroticism, and recall bias. The purpose of this study was to determine whether momentary pain assessment, compared with recalled pain reports, would diminish the influence of neuroticism and depression on the measurement of pain. METHODS: Patients with chronic pain (n=66) completed depression (Beck Depression Inventory II) and neuroticism (NEO Personality Inventory) questionnaires, made weekly recall pain ratings, judged their change in pain from 1 week to the next over a 4-week period, and collected momentary reports of pain intensity and pain unpleasantness over a 2-week period. RESULTS: Analyses showed that neuroticism and depression correlated with pain intensity and pain unpleasantness at low levels for both momentary and recalled pain reports. Neuroticism and depression did not influence the accuracy of recalled pain (difference between momentary and recalled data). Both neuroticism and depression were systematically associated with ratings of judged change in pain even when actual changes in pain were controlled. Specifically, for increased levels of baseline depression and neuroticism, patients displayed a pattern of judging recent pain as more severe than pain in the previous week following several weeks of symptom monitoring. CONCLUSION: There was little evidence for neuroticism and depression affecting either recall or momentary pain ratings or influencing the accuracy of recall ratings. However, neuroticism and depression did influence pain assessment when the task involved rating change in pain-a measure widely used in clinical research.
17712045 Proteinase 3, the Wegener autoantigen, is externalized during neutrophil apoptosis: eviden 2007 Dec 1 Proteinase 3 (PR3), a serine proteinase contained in neutrophil azurophilic granules, is considered a risk factor for vasculitides and rheumatoid arthritis when expressed on the outer leaflet of neutrophil plasma membrane and is the preferred target of antineutrophil cytoplasm autoantibodies (ANCA) in Wegener granulomatosis. ANCA binding to PR3 expressed at the surface of neutrophils activates them. Evidence is provided that neutrophil apoptosis induced significantly more membrane PR3 expression without degranulation (but no enhanced membrane CD35, CD66b, CD63, myeloperoxidase, or elastase expression). This observation was confirmed on cytoplasts, a model of granule-free neutrophils. We hypothesized that PR3 could interact with proteins involved in membrane flip-flop (eg, phospholipid scramblase 1 [PLSCR1]). PR3-PLSCR1 interaction in neutrophils was demonstrated by confocal microscopy and coimmunoprecipitation. In the RBL-2H3 rat mast-cell line stably transfected with PR3 or its inactive mutant (PR3S203A), PR3 externalization depended on PLSCR1, as shown by less PR3 externalization in the presence of rPLSCR1 siRNA, but independently of its serine-proteinase activity. Finally, apoptosis-externalized PR3 decreased the human macrophage-phagocytosis rate of apoptotic PR3 transfectants. Therefore, in addition to ANCA binding in vasculitis, the proinflammatory role of membrane PR3 expression may involve interference with macrophage clearance of apoptotic neutrophils.
17888217 Anti-cyclic citrullinated peptide antibody determination in synovial fluid of psoriatic ar 2007 Jul OBJECTIVE: To assess the role of anti-CCP antibodies in synovial fluid (SF) of psoriatic arthritis (PsA) patients by analysing their association with different clinical patterns of the disease. METHODS: Seventy-five patients with a knee-joint effusion were studied, including 31 PsA patients, 29 rheumatoid arthritis (RA) and 15 osteoarthritis (OA) patients. SF and paired serum samples were stored at -70 degrees C until IgG anti-CCP and total IgG determination. The pattern of PsA articular involvement was defined as mono-, oligo-, polyarticular or axial. RESULTS: Lower levels of IgG anti-CCP antibodies in SF (p < 0.01) and serum (p < 0.005) were found in PsA respect to RA patients without difference with OA. We found a higher SF/serum ratio for anti-CCP compared to the SF/serum ratio for total IgG in PsA (p < 0.0005) as well as in RA and OA. The correction of anti-CCP concentration in SF as IgG anti-CCP (unit) / total IgG revealed lower (p < 0.002) values in PsA patients with respect to RA patients. In PsA group, values of anti-CCP antibodies, SF/serum ratio of anti-CCP and anti-CCP/IgG above the cut-off were found in 5, 6 and 2 SF samples respectively. The presence or absence of anti-CCP antibodies did not discriminate a particular clinical subset. CONCLUSIONS: In conclusion, strengthening the concept of local production of anti-CCP antibodies within the joint space, our results suggest that anti-CCP antibody detection in SF should take into account corrections such as total amount of corresponding immunoglobulin or SF/serum ratio. In our study, the presence or absence of anti-CCP antibodies did not discriminate a particular clinical subset, but further longitudinal studies are required to clarify the clinical role of anti-CCP in PsA.
17642228 [Treatment guidelines for the use of biologics in rheumatoid arthritis; present and future 2007 Jul Application of biological agents targeting tumor necrosis factor alpha (TNFalpha) dramatically caused the paradigm shift in the treatment of rheumatoid arthritis (RA). Infliximab, a chimeric anti-TNFalpha monoclonal antibody, has initially been introduced to Japan in 2003 and shown to be dramatically effective in alleviating arthritis refractory to conventional treatment. However, serious adverse events such as bacterial pneumonia, tuberculosis and Pneumocystis jiroveci pneumonia were reported to be in relatively high incidence. Etanercept, a recombinant chimeric protein consisting of p75 TNFalpha receptor and human IgG, was subsequently introduced to Japan in 2005. The guidelines were initially designed by principle investigators (N.M, T.T, K.E) of RA study groups of the Ministry of Health, Labor and Welfare (MHLW), Japan, and approved by the Japan College of Rheumatology (JCR). We introduce the revised guidelines for the use of biologics in Japanese RA patients in this article.