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ID PMID Title PublicationDate abstract
21947744 Sensing the main health concerns in patients with established rheumatoid arthritis. 2011 Nov The principle objective was to determine the spectrum of some health concerns that are likely to be present in patients with established rheumatoid arthritis (RA) in patients living in United Arab Emirates. One hundred and one RA patients and 82 with other arthropathies, predominantly Arab individuals, were interviewed for main health concerns while receiving antirheumatic drug therapy. All were requested to indicate and prioritize their first three concerns. Setting up the list of concerns was based on previous conclusions to the question of "What bothers you most with your disease?" Pain attributed to the disease was the predominant concern in both groups: 82% vs. 71%, p=NS. Pain was also prioritized by the RA patients in the first rank, n=52/82 patients, and surpassed its prioritization in the second and third ranks combined (63.5% vs. 36.5%, p=0.001). Fear of future disability came second in RA patients, 50% vs. 25.5% in the other group, p=0.001. Depressive feeling surprisingly was more dominant in patients with other arthropathies, 35.5% vs. 20% in RA patients, p=0.001. In the prioritization of concerns, the fear of disability was first ranked by 24% of RA patients compared to 8.5% by patients with other arthropathies (p=0.009) while the latter patients were significantly concerned about depressive feeling and fatigue compared to RA patients (7% vs. 0%, p=0.007 and 14.5% vs. 5%, p=0.04, respectively). Significant hand deformities was noticed in 25 RA patients (25%); however, only 11 of those (44.5%) indicated their fear of disability compared to the others who did not (p = NS, OR = 0.73, and 95% CI 0.275-1.665). Therefore in this predominantly Arab cohort, pain is the main health concern for RA patients and patients with other arthropathies. Patients with RA are more concerned about becoming disabled, while other patients are more concerned with feeling depressed or fatigued. Those lived with phobia of disability in RA patients did that irrespective to the presence or absence of significant hand deformities.
23268367 Tabalumab, an anti-BAFF monoclonal antibody, in patients with active rheumatoid arthritis 2013 Sep 1 OBJECTIVE: To evaluate the efficacy and safety of tabalumab, a monoclonal antibody that neutralises membrane-bound and soluble B-cell activating factor (BAFF), in patients with active rheumatoid arthritis (RA) who showed inadequate response to tumour necrosis factor (TNF) inhibitors. METHODS: Patients on stable methotrexate and with inadequate response to one or more TNF inhibitors were randomised to placebo (n=35), 30 mg tabalumab (n=35) or 80 mg tabalumab (n=30) given intravenously at 0, 3 and 6 weeks. The primary outcome was the proportion of patients achieving an American College of Rheumatology 50% response (ACR50) at week 16 (all tabalumab-treated patients vs placebo). RESULTS: At week 16, no significant differences were observed in the combined tabalumab group versus placebo in ACR50 (12.7% vs 2.9%, p=0.101) or ACR20 response rates (27.0% vs 17.1%, p=0.198). However, significant differences between the combined tabalumab group and placebo were observed at earlier time points for ACR20, ACR50 and Disease Activity Score in 28 joints (DAS28)-C-reactive protein (CRP) reduction. Treatment-emergent adverse events (AEs) were similar with 30 mg tabalumab (65.7%), 80 mg tabalumab (76.7%) and placebo (71.4%), although certain events occurred more often with tabalumab than placebo (eg, infection, anaemia and gastrointestinal events). Serious AEs occurred in two (6.7%) patients receiving 80 mg tabalumab and three (8.6%) receiving placebo, with one serious infection in the placebo group. Initial increases in total and mature B cells were followed by progressive decreases, despite declines in serum tabalumab. CONCLUSIONS: At week 16, the primary end point was not achieved, but an indication of efficacy was observed at earlier time points. Safety findings for tabalumab were consistent with other biological RA therapies. CLINICAL TRIAL REGISTRATION NUMBER: NCT00689728.
22927710 Genetic markers of cardiovascular disease in rheumatoid arthritis. 2012 Cardiovascular (CV) disease is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). It is the result of an accelerated atherosclerotic process. Both RA and atherosclerosis are complex polygenic diseases. Besides traditional CV risk factors and chronic inflammation, a number of studies have confirmed the role of genetic factors in the development of the atherogenesis observed in RA. In this regard, besides a strong association between the HLA-DRB1∗04 shared epitope alleles and both endothelial dysfunction, an early step in the atherosclerotic process, and clinically evident CV disease, other polymorphisms belonging to genes implicated in inflammatory and metabolic pathways, located inside and outside the HLA region, such as the 308 variant (G > A, rs1800629) of the TNFA locus, the rs1801131 polymorphism (A > C; position + 1298) of the MTHFR locus, or a deletion of 32 base pairs on the CCR5 gene, seem to be associated with the risk of CV disease in patients with RA. Despite considerable effort to decipher the genetic basis of CV disease in RA, further studies are required to better establish the genetic influence in the increased risk of CV events observed in patients with RA.
22658359 Itraconazole: its possible role in inhibiting angiogenesis in rheumatoid arthritis. 2012 Sep Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disorder involving mainly synovial joints. It can progress to a severely debilitating form with pulmonary, renal and cardiovascular involvement. Currently, disease-modifying antirheumatic drugs (DMARDs) remain the gold standard pharmacological therapy for RA (along with nonsteroidal anti-inflammatory drugs and corticosteroids). However, DMARDs are more or less ineffective in the late phase of the disease and adverse effects often limit their use. Studies show that serum levels of vascular endothelial growth factor (VEGF) remain elevated throughout the course of RA. In experimental models, the administration of pro-angiogenic cytokines, such as VEGF or FGF, has been shown to increase the severity of the disease. Therefore, anti-angiogenic drugs such as bevacizumab (which is already being used as an anti-tumor agent) may play a significant role in longstanding RA. However, adverse effects such as hypertension, gastro-intestinal perforation and the high cost of bevacizumab are major concerns. A recent study suggests that itraconazole, an antifungal drug, has a role in selectively inhibiting angiogenesis and growth of tumor in non-small cell lung cancer. Hence, this drug may be beneficial in the treatment of RA, especially in the later phase when other modalities have failed, or as an adjuvant. To test our hypothesis, we propose a randomized, double-blinded trial in patients with longstanding RA. The control group receives the standard DMARD therapy plus placebo, while the case group receives itraconazole in addition to DMARD therapy. Serum and synovial VEGF levels, in both the control group and the case group, are compared and their correlation with the symptoms is judged. If the VEGF levels are lower and/or the symptoms are less severe in the case group, our hypothesis will be confirmed. Multi-institutional efforts are needed to confirm this hypothesis, as it is relatively new and trial data is limited.
21221689 Secondary failure to treatment with recombinant human IL-1 receptor antagonist in Chinese 2011 May The aim of this study is to assess the efficacy of anakinra, a recombinant human interleukin 1 receptor antagonist, plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) refractory to MTX therapy. A total of 54 patients with active RA, who were taking MTX at a stable dosage, were randomized to receive daily subcutaneous injections of anakinra (80 mg) or placebo. Clinical outcomes were assessed every 4 weeks for 24 weeks by using the criteria of the American College of Rheumatology. After 24 weeks, more patients achieved clinical benefits as determined by the ACR20 improvement treated with anakinra plus MTX compared with MTX alone (64% vs. 17%, P = 0.004). In the anakinra group, an ACR50 response was observed in 38% and an ACR70 response in 17%. None of the patients treated with MTX alone achieved ACR50 or ACR 70 improvement. However, nine of 42 (21.4%) patients in the anakinra group, who showed therapeutic response initially, had secondary drug failure to anakinra therapy thereafter. A significant increase in mean DAS28 from baseline was found in the non-responders to anakinra compared with placebo (0.83 ± 1.38 vs. -1.28 ± 0.78, P < 0.001). Anakinra is effective in the treatment of patients with active RA by blocking IL-1. However, the efficacy of anakinra is soon lost in about one fifth of patients in spite of initial good response.
22407780 A randomized, pilot study to assess the efficacy and safety of curcumin in patients with a 2012 Nov Curcumin is known to possess potent antiinflammatory and antiarthritic properties. This pilot clinical study evaluated the safety and effectiveness of curcumin alone, and in combination with diclofenac sodium in patients with active rheumatoid arthritis (RA). Forty-five patients diagnosed with RA were randomized into three groups with patients receiving curcumin (500 mg) and diclofenac sodium (50 mg) alone or their combination. The primary endpoints were reduction in Disease Activity Score (DAS) 28. The secondary endpoints included American College of Rheumatology (ACR) criteria for reduction in tenderness and swelling of joint scores. Patients in all three treatment groups showed statistically significant changes in their DAS scores. Interestingly, the curcumin group showed the highest percentage of improvement in overall DAS and ACR scores (ACR 20, 50 and 70) and these scores were significantly better than the patients in the diclofenac sodium group. More importantly, curcumin treatment was found to be safe and did not relate with any adverse events. Our study provides the first evidence for the safety and superiority of curcumin treatment in patients with active RA, and highlights the need for future large-scale trials to validate these findings in patients with RA and other arthritic conditions.
22268021 Perspectives on rheumatoid arthritis for the orthopedic surgeon: overview of non-tumor nec 2011 Dec Early use of disease modifying antirheumatic drug (DMARD) therapy has become the standard of care in the treatment of rheumatoid arthritis (RA). Methotrexate remains the DMARD of choice in patients without contraindications for its use. The addition of a tumor necrosis factor-α antagonist to methotrexate makes clinical remission more likely. Despite the effectiveness of this approach, some patients continue to have active disease. In these patients, the use of rituximab, abatacept, or tocilizumab provides additional options when first-line therapies inadequately control RA. For orthopedic surgeons and rheumatologists, additional therapeutic options increase the complexity of perioperative medical management. No consensus has been reached by rheumatology societies as to the optimal approach for the use of biologic and traditional DMARDs around the time of surgery. Therefore, perioperative medication management should be individualized and based on a discussion of potential risks and benefits involving patients, surgeons, and rheumatologists.
22638733 Association between the chemokine receptor 5 delta32 polymorphism and rheumatoid arthritis 2013 Mar OBJECTIVE: The aim of this study was to determine whether the functional chemokine receptor 5 delta32 (CCR5-Δ32) polymorphism confers susceptibility to rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). METHODS: Meta-analysis was conducted on associations between the CCR5-Δ32 polymorphism and RA and JIA using (1) allele contrast and (2) the recessive, (3) the dominant, and (4) the additive models. RESULTS: Eleven population comparisons based on the data obtained from nine studies involving 13,412 subjects (RA 3,848, controls 4,095; JIA 1,599, controls 3,870) were considered. In all study subjects, meta-analysis showed a significant negative association between RA and the CCR5-Δ32 allele (OR = 0.771, 95 % CI = 0.694-0.866, p = 6.5 × 10(-7)). Stratification by ethnicity indicated a significant association between the CCR5-Δ32 allele and RA in Europeans (OR = 0.8001, 95 % CI = 0.709-0.904, p = 3.2 × 10(-5)). Meta-analysis showed associations between the CCR5-Δ32 allele and JIA in Europeans and oligoarticular type (OR = 0.797, 95 % CI = 0.690-0.921, p = 0.002; OR = 0.475, 95 % CI = 0.352-0.693, p = 9.5 × 10(-8)). CONCLUSIONS: This meta-analysis demonstrates that the CCR5-Δ32 polymorphism may confer susceptibility to RA and JIA in Europeans, and suggests that the CCR5-Δ32 allele protects against the development of RA and JIA.
22661643 Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis 2013 May OBJECTIVES: To increase understanding of the aetiology and pathogenesis of rheumatoid arthritis (RA), genetic and environmental risk factors for RA subsets, defined by the presence or absence of different anticitrullinated protein/peptide antibodies (ACPAs) targeting citrullinated peptides from α-enolase, vimentin, fibrinogen and collagen type II, were investigated. METHODS: 1985 patients with RA and 2252 matched controls from the EIRA case-control cohort were used in the study. Serum samples were assayed by ELISA for the presence of anticyclic citrullinated peptides (anti-CCP) antibodies and four different ACPA fine specificities. Cross-reactivity between ACPAs was examined by peptide absorption experiments. Genotyping was performed for HLA-DRB1 shared epitope (SE) alleles and the PTPN22 gene, while information regarding smoking was obtained by questionnaire. The association of genetic and environmental risk factors with different subsets of RA was calculated by logistic regression analysis. RESULTS: Limited cross-reactivity was observed between different ACPA fine specificities. In total, 17 RA subsets could be identified based on their different ACPA fine specificity profiles. Large differences in association with genetic and environmental determinants were observed between subsets. The strongest association of HLA-DRB1 SE, PTPN22 and smoking was identified for the RA subset which was defined by the presence of antibodies to citrullinated α-enolase and vimentin. CONCLUSION: This study provides the most comprehensive picture to date of how HLA-DRB1 SE, PTPN22 and smoking are associated with the presence of specific ACPA reactivities rather than anti-CCP levels. The new data will form a basis for molecular studies aimed at understanding disease development in serologically distinct subsets of RA.
21976063 Elevated levels of serum antibodies against alpha-1, 6-glucan in patients with systemic lu 2011 Sep This study was undertaken to investigate whether levels of anti-alpha-1, 6-glucan antibodies in human sera correlate with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Serum samples were collected from patients with SLE (n = 30), RA (n = 30) and healthy adult volunteers. IgG, IgA and IgM levels against alpha-1, 6-glucan were measured using enzyme linked immunosorbent assays. Anti-alpha-1, 6-glucan IgG prevalence was raised in patients with active SLE (73.3%) and RA (60%) compared with healthy controls (13.3%). Strong correlation between anti-alpha-1,6-glucan-IgG levels and anti-perinuclear factor (r = 0.642; p < 0.05) in RA patients or anti-nuclear antibodies (r = 0.675; p < 0.05) in SLE patients was observed. No significant differences in anti-alpha-1,6-glucan-IgA or-IgM levels were noted between different groups. We conclude that anti-alpha-1,6-glucan-IgG levels were significantly elevated in patients with SLE or RA and positively correlated with disease activity.
21527853 Blockage of TNF-α by infliximab reduces CCL2 and CCR2 levels in patients with rheumatoid 2011 Aug OBJECTIVES: To investigate the mechanism in vivo for the regulation of inflammation of patients with RA by infliximab, we measured serum levels of chemokine ligand (CCL) 2, CCL3, CXCL8, and expression of CCL2 receptor chemokine receptor (CCR) 2 on CD4 T cells from patients with rheumatoid arthritis (RA). METHODS: Forty-four patients with were enrolled in our study. Twenty-four patients received infliximab combined with methotrexate. Twenty patients received methotrexate alone. Serum levels of the chemokines CCL2, CCL3, and CXCL8 were quantified using commercial enzyme-linked immunosorbent assay kits. Flow cytometry was used to analyze the expression of CCR2 on CD4 T cells. RESULTS: The mean CCL2 levels in the infliximab-treated patients decreased significantly from 885.20 ± 323.52 pg/mL at pretreatment to 454.65 ± 185.03 pg/mL (P < 0.05) at 30 weeks after the initial treatment. Fluorescence density of CCR2 expression on CD4 T cells were significantly reduced after infliximab treatment. CONCLUSIONS: CCL2/CCR2 system in patients with active RA may be sensitive to anti-tumor necrosis factor-α therapy and suggest that CCL2 plays a crucial role in the pathogenesis of RA. CCR2 may be an important target for therapy in RA.
22530757 The periodontium of periodontitis patients contains citrullinated proteins which may play 2012 Jul AIM: To determine the presence and location (stroma versus epithelium) of citrullinated proteins in periodontitis tissue as compared to non-periodontitis tissue and synovial tissue of RA patients. MATERIALS & METHODS: Periodontitis, healthy periodontal and RA-affected synovial tissue samples were collected in addition to buccal swabs. These samples were stained for the presence of citrullinated proteins using polyclonal (Ab5612) and monoclonal (F95) antibodies. Furthermore, Western blotting with F95 was performed on lysates prepared from periodontal and synovial tissues. RESULTS: In periodontitis stroma, increased citrullinated protein presence (80%) was observed compared with control stroma (33%), the latter was associated with inflammation of non-periodontitis origin. Periodontal epithelium always stained positive for Ab5612. Noteworthy, only periodontitis-affected epithelium stained positive for F95. All buccal mucosal swabs and 3 of 4 synovial tissue samples stained positive for both Ab5612 and F95. Western blotting with F95 showed presence of similar citrullinated proteins in both periodontitis and RA-affected synovial tissue. CONCLUSION: Within the periodontal stroma, citrullination is an inflammation-depended process. In periodontal epithelium, citrullination is a physiological process. Additional citrullinated proteins are formed in periodontitis, apparently similar to those formed in RA-affected synovial tissue. Periodontitis induced citrullination may play a role in the aetiology of rheumatoid arthritis.
21435232 TWEAK and Fn14 expression in the pathogenesis of joint inflammation and bone erosion in rh 2011 Mar 24 INTRODUCTION: TNF-like weak inducer of apoptosis (TWEAK) has been proposed as a mediator of inflammation and bone erosion in rheumatoid arthritis (RA). This study aimed to investigate TWEAK and TWEAK receptor (Fn14) expression in synovial tissue from patients with active and inactive rheumatoid arthritis (RA), osteoarthritis (OA) and normal controls and assess soluble (s)TWEAK levels in the synovial fluids from patients with active RA and OA. Effects of sTWEAK on osteoclasts and osteoblasts were investigated in vitro. METHODS: TWEAK and Fn14 expression were detected in synovial tissues by immunohistochemistry (IHC). Selected tissues were dual labelled with antibodies specific for TWEAK and lineage-selective cell surface markers CD68, Tryptase G, CD22 and CD38. TWEAK mRNA expression was examined in human peripheral blood mononuclear cells (PBMC) sorted on the basis of their expression of CD22. sTWEAK was detected in synovial fluid from OA and RA patients by ELISA. The effect of sTWEAK on PBMC and RAW 264.7 osteoclastogenesis was examined. The effect of sTWEAK on cell surface receptor activator of NF Kappa B Ligand (RANKL) expression by human osteoblasts was determined by flow cytometry. RESULTS: TWEAK and Fn14 expression were significantly higher in synovial tissue from all patient groups compared to the synovial tissue from control subjects (P < 0.05). TWEAK was significantly higher in active compared with inactive RA tissues (P < 0.05). TWEAK expression co-localised with a subset of CD38+ plasma cells and with CD22+ B-lymphocytes in RA tissues. Abundant TWEAK mRNA expression was detected in normal human CD22+ B cells. Higher levels of sTWEAK were observed in synovial fluids isolated from active RA compared with OA patients. sTWEAK did not stimulate osteoclast formation directly from PBMC, however, sTWEAK induced the surface expression of RANKL by human immature, STRO-1+ osteoblasts. CONCLUSIONS: The expression of TWEAK by CD22+ B cells and CD38+ plasma cells in RA synovium represents a novel potential pathogenic pathway. High levels of sTWEAK in active RA synovial fluid and of TWEAK and Fn14 in active RA tissue, together with the effect of TWEAK to induce osteoblastic RANKL expression, is consistent with TWEAK/Fn14 signalling being important in the pathogenesis of inflammation and bone erosion in RA.
21217016 Th17 cells, not IL-17+ γδ T cells, drive arthritic bone destruction in mice and humans. 2011 Feb 15 The mechanism whereby IL-17 drives rheumatoid arthritis remains incompletely understood. We demonstrate that anti-IL-17 therapy in collagen-induced arthritis ameliorates bone damage by reducing the number of osteoclasts in joints. We found equal numbers of CD4(+) Th17 and IL-17 producing γδ T cells in the joints of arthritic mice, and in vitro, both populations similarly induced osteoclastogenesis. However, individual depletion and adoptive transfer studies revealed that in vivo, Th17 cells dominated with regard to bone destruction. Unlike γδ T cells, Th17 cells were found in apposition to tartrate-resistant acid phosphatase positive osteoclasts in subchondral areas of inflamed joints, a pattern reproduced in patient biopsies. This localization was caused by Ag-specific retention, because OVA-primed Th17 cells showed a γδ T cell-like diffuse distribution. Because IL-23, as produced by osteoclasts, enhanced T cell-mediated osteoclastogenesis, we propose that Ag-specific juxtaposition is key to foster the molecular cross talk of Th17 cells and osteoclasts, thus driving arthritic bone destruction.
21659506 NC4 Domain of cartilage-specific collagen IX inhibits complement directly due to attenuati 2011 Aug 12 Collagen IX containing the N-terminal noncollagenous domain 4 (NC4) is unique to cartilage and a member of the family of fibril-associated collagens with both collagenous and noncollagenous domains. Collagen IX is located at the surface of fibrils formed by collagen II and a minor proportion of collagen XI, playing roles in tissue stability and integrity. The NC4 domain projects out from the fibril surface and provides sites for interaction with other matrix components such as cartilage oligomeric matrix protein, matrilins, fibromodulin, and osteoadherin. Fragmentation of collagen IX and loss of the NC4 domain are early events in cartilage degradation in joint diseases that precedes major damage of collagen II fibrils. Our results demonstrate that NC4 can function as a novel inhibitor of the complement system able to bind C4, C3, and C9 and to directly inhibit C9 polymerization and assembly of the lytic membrane attack complex. NC4 also binds the complement inhibitors C4b-binding protein and factor H and enhances their cofactor activity in degradation of activated complement components C4b and C3b. NC4 interactions with fibromodulin and osteoadherin inhibited binding to C1q and complement activation by these proteins. Taken together, our results suggest that collagen IX and its interactions with matrix components are important parts of a machinery that protects the cartilage from complement activation and chronic inflammation seen in diseases like rheumatoid arthritis.
22312919 [The analytic and diagnostic characteristics of the national test system detecting cyclic 2011 Nov The clinical signifcance of serodiagnostic assay of rheumatoid arthritis increased nowadays. This is a reason to include the citrullinated antigens' antibodies into the new criteria of diagnostics ACR/EULAR 2010. The approbation of national test system detecting the cyclic citrullinated peptide antibodies was implemented. The analysis was applied to 211 blood serum samples taken of 50 blood donors, 60 patients with rheumatoid arthritis, 66 patients with other rheumatoid diseases. In addition, 35 samples were concurrently analyzed with the comparative test system (CCP2 Euroimmun, Germany). The referential meanings of standard limits were established on the basis of results of study of samples taken from healthy blood donors. When the standard limit was less than 10 arbitrary units the sensitivity made up 75% and the specificity--87.9%. In the case of higher values of citrullinated antigens' antibodies which are more than 15 arbitrary units, the sensitivity made up 68% and the specificity--93.1%. The results of comparing with the comparative test system characterized by high convergence made up 94% (33 out of 35), but the comparative test system detected citrullinated antigens' antibodies in 2 samples. The positive qualitative results of both methods analysis of autoantibodies weakly correlated with one another (r = 0.14). The results testify that the parameters of national test system correspond to the publication data concerning the second generation methods of cyclic citrullinated peptide antibodies detection though yield to the best foreign analogues.
21821867 Delays in assessment of patients with rheumatoid arthritis: variations across Europe. 2011 Oct OBJECTIVE: The first 3 months after symptom onset represent an important therapeutic window for rheumatoid arthritis (RA). This study investigates the extent and causes of delay in assessment of patients with RA in eight European countries. METHOD: Data on the following levels of delay were collected from 10 centres (Berlin, Birmingham, Heraklion, Lund, Prague, Stockholm, Umeå, Vienna, Warsaw and Zurich): (1) from onset of RA symptoms to request to see healthcare professional (HCP); (2) from request to see HCP to assessment by that HCP; (3) from initial assessment by HCP to referral to rheumatologist; and (4) from referral to rheumatologist to assessment by that rheumatologist. RESULTS: Data were collected from 482 patients with RA. The median delay across the 10 centres from symptom onset to assessment by the rheumatologist was 24 weeks, with the percentage of patients seen within 12 weeks of symptom onset ranging from 8% to 42%. There were important differences in the levels underlying the total delays at individual centres. CONCLUSIONS: This research highlights the contribution of patients, professionals and health systems to treatment delay for patients with RA in Europe. Although some centres have strengths in minimising certain types of delay, interventions are required in all centres to ensure timely treatment for patients.
22350574 Fungal arthritis of the wrist caused by Candida parapsilosis during infliximab therapy for 2012 Nov A 60-year-old woman with rheumatoid arthritis, who had been treated with infliximab, presented with uncontrollable wrist arthritis. Fungal arthritis caused by Candida parapsilosis was confirmed by examining her aspirated joint fluid. Her infliximab therapy was interrupted, and antifungal therapy with fluconazole was started. After the fungal infection had been ameliorated, surgical debridement and arthrodesis of the wrist joint were conducted, and her symptoms completely resolved. Although fungal arthritis is rare, it should be considered as a differential diagnosis of exacerbated monoarthritis in patients treated with biological agents.
22129793 TGF beta1 polymorphisms are candidate predictors of the clinical response to rituximab in 2012 Oct OBJECTIVE: To evaluate the association between several candidate single-nucleotide polymorphisms (SNPs) and responsiveness to rituximab in patients with rheumatoid arthritis (RA). METHODS: Sixty-three RA patients were included. Nine genes (13 SNPs) were subsequently analyzed, including those coding for cytokines involved in synovitis (IL10, LTA, TGFβ1, TNF-α, TNF receptor II) and genes associated with RA susceptibility (-C5 TRAF1, STAT4, TNFAIP3 and PTPN22). RESULTS: Forty-four patients were defined as responders and 19 as nonresponders. TGFβ1 Codon 10 and TGFβ1 Codon 25 SNPs were both associated with clinical response (probability to respond to treatment with the Codon 10C/T genotype: OR = 1.6; P = 0.002, and with the Codon 25 G/C genotype: OR = 1.6; P = 0.025). The probability to be a responder when the TGFβ Codon10 C/T and TGFβ Codon 25 G/C genotypes were co-inherited, doubled (OR = 2.6; P = 0.008). CONCLUSION: The TGFβ1 SNPs are associated with a good response to rituximab therapy and as such could be useful genetic biomarkers in predicting therapy outcome.
22238051 Increased IgG on cell-derived plasma microparticles in systemic lupus erythematosus is ass 2012 Apr OBJECTIVE: To quantify immunoglobulin and C1q on circulating cell-derived microparticles (MPs) in patients with systemic lupus erythematosus (SLE) and to determine whether immunoglobulin and C1q levels are correlated with clinical and serologic parameters. METHODS: Sixty-eight clinically well-characterized SLE patients, 38 healthy controls, 6 patients with systemic sclerosis (SSc), and 6 patients with rheumatoid arthritis (RA) were included. The numbers of annexin V-binding MPs displaying IgG, IgM, or C1q were enumerated by flow cytometry. MP protein levels were determined by mass spectrometry in clinically defined subsets of SLE patients and controls. The MP IgG load was determined by flow cytometric analysis of all samples from SLE patients and healthy controls. RESULTS: SLE patients had significantly increased total and relative numbers of IgG-positive MPs (P = 0.0004), with a much higher average IgG load per MP (P < 0.0001) than healthy controls. Quantitative mass spectrometry of purified MPs verified significantly increased IgG, IgM, and C1q levels in SLE patients. In RA and SSc patients, the average IgG load per MP was significantly lower than in SLE patients (P = 0.006 and P = 0.05, respectively). Also, the IgM load and C1q load per MP were significantly higher in SLE patients than in the control groups (P < 0.05), except for IgM in the RA group. IgG-positive MPs were significantly associated with the presence of anti-double-stranded DNA, anti-extractable nuclear antigen, and antihistone antibodies, with total IgG, and with decreased leukocyte counts. Average IgG load per MP was associated with lower concentrations of MPs, the presence of anti-C1q antibodies, and complement consumption. CONCLUSION: Our findings indicate that circulating cell-derived MPs in SLE patients carry increased loads of IgG, IgM, and C1q and that IgG MPs are associated with autoantibodies and complement activation. The findings link immunologic reactions on MPs with the etiology of SLE.