Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 25779027 | Role of EFNB1 and EFNB2 in Mouse Collagen-Induced Arthritis and Human Rheumatoid Arthritis | 2015 Jul | OBJECTIVE: EFNB1 and EFNB2 are ligands for Eph receptor tyrosine kinases. This study was undertaken to investigate how the expression of Efnb1 and Efnb2 on murine T cells influences the pathogenesis of collagen-induced arthritis (CIA) and to assess correlations between the T cell expression of these 2 molecules and measures of disease activity in patients with rheumatoid arthritis (RA). METHODS: CIA was studied in mice with T cell-specific deletion (double gene knockout [dKO]) of both Efnb1 and Efnb2. Expression of EFNB1 and EFNB2 messenger RNA (mRNA) in peripheral blood T cells from patients with RA was determined by quantitative reverse transcription- polymerase chain reaction. RESULTS: In dKO mice, clinical scores of arthritis were reduced compared to those in wild-type (WT) control mice. Serum collagen-specific antibody titers in dKO mice were lower than those in WT mice. In analyses based on equal cell numbers, dKO mouse T cells, as compared to WT mouse T cells, provided vastly inferior help to B cells in the production of collagen-specific antibodies in vitro. T cells from dKO mice were compromised in their ability to migrate to the arthritic paws in vivo and in their ability to undergo chemotaxis toward CXCL12 in vitro. Deletion mutation of Efnb1 and Efnb2 intracellular tails revealed critical regions in controlling T cell chemotaxis. T cells from RA patients expressed higher EFNB1 mRNA levels, which correlated with RA symptoms and laboratory findings. CONCLUSION: Efnb1 and Efnb2 in T cells are essential for pathogenic antibody production and for T cell migration to the inflamed paws in mice with CIA. These findings suggest that the expression of EFNB1 in T cells might be a useful parameter for monitoring RA disease activity and treatment responses. | |
| 27413250 | Krüppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast-Like Syno | 2016 | Human fibroblast-like synoviocytes play a vital role in joint synovial inflammation in rheumatoid arthritis (RA). Proinflammatory cytokines induce fibroblast-like synoviocyte activation and dysfunction. The inflammatory mediator Krüppel-like factor 4 is upregulated during inflammation and plays an important role in endothelial and macrophage activation during inflammation. However, the role of Krüppel-like factor 4 in fibroblast-like synoviocyte activation and RA inflammation remains to be defined. In this study, we identify the notion that Krüppel-like factor 4 is higher expressed in synovial tissues and fibroblast-like synoviocytes from RA patients than those from osteoarthritis patients. In vitro, the expression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes is induced by proinflammatory cytokine tumor necrosis factor-α. Overexpression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes robustly induced interleukin-6 production in the presence or absence of tumor necrosis factor-α. Conversely, knockdown of Krüppel-like factor 4 markedly attenuated interleukin-6 production in the presence or absence of tumor necrosis factor-α. Krüppel-like factor 4 not only can bind to and activate the interleukin-6 promoter, but also may interact directly with nuclear factor-kappa B. These results suggest that Krüppel-like factor 4 may act as a transcription factor mediating the activation of fibroblast-like synoviocytes in RA by inducing interleukin-6 expression in response to tumor necrosis factor-α. | |
| 24879909 | CROSS-CULTURAL VALIDATION OF THE PORTUGUESE VERSION OF THE EDUCATIONAL NEEDS ASSESSMENT TO | 2015 Jul | OBJECTIVES: To undertake a cross-cultural adaptation and validation of the educational needs assessment tool (ENAT) into Portuguese. METHODS: The first phase of this research (cross-cultural adaptation) utilised a well-established translation method comprising five sequential steps: forward-translation, synthesis of translations, back-translation, expert committee and field-testing of the adapted version. The second phase involved collecting data from 123 patients and subjecting them to Rasch analysis for validity testing including cross-cultural invariance. RESULTS: The translation and field-testing phase went smoothly giving rise to minor adjustments in the phrasing of some items. The preliminary analysis of the 39 items, revealed some deviations from the model with the overall item-person interaction fit statistics ï£2(df) = 56.025 (39), p = 0.038. Significant item-item correlations caused artificial inflation of the internal consistency, therefore violating the model assumption of local independence of items. To correct this, all locally dependent items were then grouped into their respective domains, creating a 7 testlet-scale which demonstrated a good fit to the Rasch model, ï£2(df) = 2.625 (7), p = 0.917 and internal consistency PSI = 0.975. Analysis of the pooled (Portuguese and the English) data revealed cross-cultural DIF, requiring adjustments in two testlets: 'treatments' and 'support' which ensured cross-cultural equivalence. CONCLUSIONS: This study confirms the Portuguese ENAT is a robust unidimensional tool with which to assess the educational needs of Portuguese people with RA. Cross-cultural adjustments are required only if the data from Portugal and the UK are pooled or compared. The tool is now available for use in clinical practice and research. | |
| 27534979 | Cardiovascular risk assessment and treatment in chronic inflammatory disorders in primary | 2016 Dec 15 | OBJECTIVE: To compare differences in cardiovascular (CV) risk factors assessment and management among patients with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) with that of matched controls. METHODS: A matched cohort study was conducted using primary care electronic health records for one London borough. All patients diagnosed with RA or IBD, and matched controls registered with local general practices on 12th of January 2014 were identified. The study compared assessment and treatment of CV risk factors (blood pressure, body mass index, cholesterol and smoking) in the year before, the year after, and 5 years after RA and IBD diagnosis. RESULTS: A total of 1121 patients with RA and 1875 patients with IBD were identified and matched with 4282 and, respectively, 7803 controls. Patients with RA were 25% (incidence rate ratio, 1.25, 95% CI 1.12 to 1.35) more likely to have a CV risk factor measured compared with matched controls. The difference declined to 8% (1.08, 1.04 to 1.14) over 5 years of follow-up. The corresponding figures for IBD were 26% (1.26, 1.16 to 1.38) and 10% (1.10, 1.05 to 1.15). Patients with RA showed higher antihypertensive prescription rates during 5 years of follow-up (OR, 1.37, 95% CI 1.14 to 1.65) and patients with IBD showed higher statin prescription rates in the year preceding diagnosis (2.30, 1.20 to 4.42). Incomplete CV risk assessment meant that QRISK scores could be calculated for less than a fifth (17%) and clinical recording of CV disease (CVD) risk scores among patients with RA and IBD was 11% and 6%, respectively. CONCLUSIONS: The assessment and treatment of vascular risk in patients with RA and IBD in primary care is suboptimal, particularly with reference to CVD risk score calculation. | |
| 25431484 | Tight control of rheumatoid arthritis in a resource-constrained setting: a randomized cont | 2015 Jun | OBJECTIVE: The aim of this study was to explore the clinical utility of the clinical disease activity index (CDAI). We compared the disease control with protocolized treatment adjustment following a tight control strategy utilizing either the simplified disease activity index (SDAI) or the CDAI. METHODS: In a prospective 12 month study, DMARD-naive RA patients were randomized to either a CDAI or SDAI arm and were treated with traditional DMARDs, increased on a monthly basis according to a predefined protocol to achieve low disease activity. RESULTS: Of 102 patients (84 females, 96 Black Africans), the mean symptom duration was 3.0 years (s.d. 3.8) and the mean 28-joint DAS (DAS28) at baseline was 6.2 (s.d. 1.2). By 12 months, the proportion of patients in the CDAI and SDAI groups achieving low disease activity (30% and 32%) and remission (33 and 34%) were similar. There were no significant differences in the mean DAS28 or its components or in HAQ Disability Index or health-related quality of life scores. Baseline predictors of low disease activity at 12 months were shorter symptom duration (P = 0.03) and lower HAQ-DI score (P = 0.04). CONCLUSION: Given that the CDAI performed as well as the SDAI, and considering the cost savings and convenience because no acute phase reactant test is necessary, we suggest the CDAI may be an appropriate tool for monthly disease activity monitoring as part of a tight control strategy in developing countries. | |
| 26702052 | Preferential Induction of the T Cell Auxiliary Signaling Molecule B7-H3 on Synovial Monocy | 2016 Feb 19 | B7-H3, a newly identified B7 family member, has functional duality as a co-stimulator and co-inhibitor that fine-tunes T cell-mediated immune responses. Given that B7-H3 expression on human monocytes and dendritic cells is enhanced by inflammatory cytokines, its potential inmmunoregulatory role at sites of inflammation has been suggested. Further, monocytes play crucial roles in the pathophysiology of various inflammatory disorders including autoimmune diseases; however, the immunological role of B7-H3 in rheumatoid arthritis (RA) has not been defined. Thus, we aimed to investigate the possible roles of monocyte B7-H3 in the pathogenesis of RA. Synovial monocytes, but not peripheral monocytes, in RA patients predominantly express surface B7-H3. The 4Ig isoform of B7-H3 is exclusively induced on the cell surface, whereas the 2Ig B7-H3 isoform is constitutively expressed in the intracytoplasmic region of both peripheral and synovial monocytes. B7-H3 knockdown experiments reveal that surface B7-H3 has an inhibitory effect on IFN-γ production in CD4 memory cells. Moreover, surface B7-H3 expression on synovial monocytes inversely correlates with RA clinical parameters. Our findings demonstrate that activation-induced B7-H3 expression on synovial monocytes has the potential to inhibit Th1-mediated immune responses and immunomodulatory roles affecting RA pathogenesis. | |
| 25240765 | Increased plasma IL-17F levels in rheumatoid arthritis patients are responsive to methotre | 2015 Feb | The aims of this study are to compare plasma levels of IL17A, A/F, and F biomarkers in RA patients versus controls, and to determine responsiveness to methotrexate (MTX), anti-TNFs, and abatacept. We selected plasma samples from RA cohorts consisting of a cross-sectional RA cohort (N = 78) not receiving DMARDs at the time of sampling, as well as from longitudinal drug start cohorts (N = 71 patients) with pre/post samples including anti-TNF, abatacept, and MTX-treated patients. We assayed IL-17A, IL-17F, and IL17-A/F using a highly sensitive immunoassay system. Plasma levels of IL-17A, IL-17A/F, and IL-17F were all significantly increased in RA versus controls. The difference was largest in IL-17F, with median IL-17F levels in RA patients being approximately 18-fold higher than controls (81 pg/mL in RA vs. 4.4 pg/mL in controls, p < 0.001). Among the forms of IL-17, only IL-17F was decreased after therapy in the MTX cohort (p = 0.006), abatacept cohort (p < 0.001), and anti-TNF cohorts (p = 0.02), whereas IL-17A and IL-17A/F were not significantly decreased for any of the three drug cohorts. Synovial fluid analysis demonstrated higher IL-17F levels in RA (p = 0.016) than healthy controls. These results suggest a specific role for IL-17F in human RA pathogenesis and as a therapeutic target. | |
| 27036118 | Human embryonic stem cell-derived mesenchymal stromal cells ameliorate collagen-induced ar | 2016 Apr 1 | BACKGROUND: The immunosuppressive and anti-inflammatory properties of mesenchymal stromal cells (MSC) have prompted their therapeutic application in several autoimmune diseases, including rheumatoid arthritis. Adult MSC are finite and their clinical use is restricted by the need for long-term expansion protocols that can lead to genomic instability. Inhibition of Smad2/3 signaling in human pluripotent stem cells (hPSC) provides an infinite source of MSC that match the phenotype and functional properties of adult MSC. Here, we test the therapeutic potential of hPSC-MSC of embryonic origin (embryonic stem cell-derived mesenchymal stromal cells, hESC-MSC) in the experimental model of collagen-induced arthritis (CIA). METHODS: CIA was induced in DBA/1 mice by immunization with type II collagen (CII) in Complete Freund's Adjuvant (CFA). Mice were treated with either a single dose (10(6) cells/mouse) of hESC-MSC on the day of immunization (prophylaxis) or with three doses of hESC-MSC every other day starting on the day of arthritis onset (therapy). Arthritis severity was evaluated daily for six weeks and ten days, respectively. Frequency of Treg (FoxP3(+)), Th1 (IFNγ(+)) and Th17 (IL17(+)) CD4(+) T cells in inguinal lymph nodes (ILN) was quantified by flow cytometry. Serum levels of anti-CII antibodies were determined by ELISA. Detection of hESC-MSC and quantification of murine and human indoleamine 2,3 dioxygenase (IDO1) expression was performed by quantitative real-time PCR. Statistical differences were analyzed by ANOVA and the Mann-Whitney U test. RESULTS: Administration of hESC-MSC to mice with established arthritis reduced disease severity compared to control-treated mice. Analysis of CD4 T cell populations in treated mice showed an increase in FoxP3(+) Treg and IFNγ(+) Th1 cells but not in Th17 cells in the ILN. Anti-CII antibody levels were not affected by treatment. Migration of hESC-MSC to the ILN in treated mice was associated with the induction of murine IDO1. CONCLUSION: Treatment with hESC-MSC ameliorates CIA by inducing IFNγ(+) Th1 cells and IDO1 in the host. Thus, hESC-MSC can provide an infinite cellular source for treatment of rheumatoid arthritis. | |
| 25149278 | Combined effects of infliximab and methotrexate on rheumatoid arthritis osteoblastic cell | 2015 Aug | The goal of this study is to investigate the in vitro effects of two disease-modifying anti-rheumatic drugs, largely used in the treatment of rheumatoid arthritis (RA), [infliximab (IFX) and methotrexate (MTX)], in RA primary osteoblast cell cultures. MTX inhibited proliferation and metabolic activity in RA osteoblasts was able to increase apoptosis. Conversely, IFX increased the proliferation, osteocalcin production and the alkaline phosphatase activity. Interestingly, IFX appeared to antagonise the negative effect exerted by MTX. Both drugs significantly reduced the IL-6 production in osteoblasts when used alone, and the combination of the two agents resulted in a significant additional reduction of IL-6 synthesis, with an apparent additive effect. The present study suggests that MTX exerts negative direct effects on bone metabolism in RA patients, but the combined treatment with anti-TNF-α can be beneficial for the interaction of MTX with bone cells. | |
| 26276872 | 1,25(OH)2D3 Promotes the Efficacy of CD28 Costimulation Blockade by Abatacept. | 2015 Sep 15 | Inhibition of the CD28:CD80/CD86 T cell costimulatory pathway has emerged as an effective strategy for the treatment of T cell-mediated inflammatory diseases. However, patient responses to CD28-ligand blockade by abatacept (CTLA-4-Ig) in conditions such as rheumatoid arthritis are variable and often suboptimal. In this study, we show that the extent to which abatacept suppresses T cell activation is influenced by the strength of TCR stimulation, with high-strength TCR stimulation being associated with relative abatacept insensitivity. Accordingly, cyclosporin A, an inhibitor of T cell stimulation via the TCR, synergized with abatacept to inhibit T cell activation. We also observed that 1,25-dihydroxyvitamin D3 enhanced the inhibition of T cell activation by abatacept, strongly inhibiting T cell activation driven by cross-linked anti-CD3, but with no effect upon anti-CD28 driven stimulation. Thus, like cyclosporin A, 1,25-dihydroxyvitamin D3 inhibits TCR-driven activation, thereby promoting abatacept sensitivity. Vitamin D3 supplementation may therefore be a useful adjunct for the treatment of conditions such as rheumatoid arthritis in combination with abatacept to promote the efficacy of treatment. | |
| 25293500 | Correlation of structural abnormalities of the wrist and metacarpophalangeal joints evalua | 2015 Jul | AIM: In rheumatoid arthritis (RA) hands, we applied high-resolution peripheral quantitative computed tomography (HR-pQCT) and 3 Tesla (3 T) magnetic resonance imaging (MRI), which are new methods for erosion detection and bone marrow edema (BME) quantification. We compared the erosion measurements between these techniques with conventional radiographs (CR) in order to examine their significance for evaluating structural abnormalities. METHODS: In 16 RA patients, HR-pQCT of metacarpophalangeal and wrist joints, 3 T MRI of wrist joints, as well as CR in both hands and feet were performed. Ten patients had 1-year follow-up CR. CRs were graded according to the modified Sharp score (MSS). Bone erosions were evaluated in HR-pQCT and MRI. BME pattern was quantified from MRI for volume, signal change and total burden. RESULTS: The erosion detection sensitivity of MRI was 85.7% and CR was 60.9% when HR-pQCT was considered as a reference method. The smallest dimensions of erosion detected by HR-pQCT, MRI and CR were 0.09, 0.14 and 0.66 cm, respectively. Baseline total MSS was correlated with HR-pQCT erosion measures, MRI erosion measures and MRI BME volume (P < 0.05). The mean difference between baseline and 1-year follow-up MSS (delta MSS) was 1.2. A trend was observed toward a correlation between delta MSS and MRI BME volume and burden. CONCLUSION: This study demonstrates that HR-pQCT detects more and smaller bone erosions compared to MRI and CR. In addition, 3 T MRI can provide quantitative measurement of BME. Combination of HR-pQCT and MRI modalities may provide powerful tools to evaluate joint inflammation and bone damage in RA. | |
| 27974105 | Anti-TNF treatment response in rheumatoid arthritis patients with moderate disease activit | 2017 Jan | OBJECTIVES: Rheumatoid arthritis (RA) patients with moderate disease activity show progression of joint damage and have impaired quality of life, physical function, work and daily activities. Little is known about management of patients with moderate RA. The aim of the study was to assess the 1-year response to anti-TNF in biologic-naïve RA patients with moderate (3.2 |
|
| 27383049 | Safety profile of repeated rituximab cycles in unselected rheumatoid arthritis patients: a | 2016 Sep | OBJECTIVES: To evaluate the long-term safety of rituximab (RTX) in rheumatoid arthritis (RA) patients in daily clinical practice. METHODS: This was a multicentre (17 Greek Rheumatology sites), prospective, long-term, pharmacovigilance study of patients with moderate to severe RA and an inadequate response or intolerance to ≥1 anti-tumour necrosis factor (TNF) agents. Adverse events (AEs) were recorded and collected prospectively every 2-6 months. RESULTS: 234 patients (mean age: 59±12.5, 79.5% women, mean DAS28: 5.35±1.32) were included and followed for 27.7 months (median). The overall AEs, serious AE (SAEs) and serious infection (SIEs) rate were 48.36, 6.68 and 2.53/100 patient-years, respectively. Three cases of hepatitis B virus (HBV) reactivation were recorded (two in chronic and one in past HBV infection). Withdrawals due to AEs (5.6%) occurred more frequently during the first cycles of RTX therapy while repeated RTX cycles were not associated with an increased risk of AEs. There were 3 deaths with an incidence rate of 0.69/100 patient-years. Age ≥65 years was associated with a higher incidence rate ratio of AEs and SAEs as compared to <65 years (1.53, p=0.002 and 2.88, p=0.005, respectively). Drug retention rate during 434.28 patient-years of follow-up was 57.3%. Factors associated with drug discontinuation by multivariate analysis included age, baseline swollen joint count and no use of concomitant methotrexate therapy. CONCLUSIONS: Long-term RTX therapy in a real-life RA cohort, did not reveal any new safety issues. Advanced age was associated with increased risk of AEs and premature drug discontinuation. | |
| 25661469 | Young people's decisions about biologic therapies: who influences them and how? | 2015 Jul | OBJECTIVES: Young people with inflammatory arthritis can have severe disease warranting biologic therapy. They face complex treatment decisions, with profound consequences. This study aimed to explore the influence of individuals outside the care team (trusted others) on the treatment decisions made by young people, in particular their decisions about biologic therapies. METHODS: Young people (16-25 years of age) with inflammatory arthritis and experience of treatment decision making were recruited from three NHS Hospital Trusts. Twenty-five were interviewed, plus 11 trusted others identified by young people as being involved in their decision making, as well as 6 health professionals. The data were analysed using coding, memoing and mapping techniques and the findings were tested through a series of focus groups. RESULTS: Young people initially emphasized their decisional autonomy, typically describing people other than health professionals as limited in influence. However, discussions revealed the involvement--in deliberation and enactment--of a range of other people. This cast of trusted others was small and largely consistent; mothers played a particularly prominent role, providing cognitive, practical and emotional support. Members of the wider cast of trusted others were involved in more limited but still significant ways. CONCLUSION: Young people claim autonomy but other people enable this. The network of relationships in which they are embedded is distinctive and evolving. Mothers play a supporting role well into early adulthood; in contrast, partners are involved in far more limited ways. As such, the applicability of adult models of decision making is unclear. This must be taken into account if the support provided by professionals is to be optimally tailored to young people's needs. | |
| 27604532 | Intramuscular versus ultrasound-guided intratenosynovial glucocorticoid injection for teno | 2017 Apr | OBJECTIVE: The aim of this study was to compare the efficacy of intramuscular versus ultrasound (US)-guided intratenosynovial glucocorticoid injection in providing disease control after 2, 4 and 12 weeks in patients with rheumatoid arthritis(RA) with tenosynovitis. METHODS: Fifty patients with RA and tenosynovitis were randomised into two double-blind groups: (A) 'intramuscular group', receiving intramuscular injection of betamethasone and US-guided intratenosynovial isotonic saline injection and (B) 'intratenosynovial group' receiving saline intramuscularly and US-guided intratenosynovial betamethasone injection. All patients were in stable disease-modifying anti-rheumatic drug treatment prior to and during the study. Patients were excluded, and considered non-responders, if any treatments were altered during the follow-up period. 'US tenosynovitis remission', defined as US tenosynovitis grey-scale score ≤1 and colour Doppler score=0, was assessed at week 4 (primary outcome), and weeks 2 and 12, using non-responder imputation for missing data. RESULTS: US tenosynovitis remission at week 4 was achieved in 25% (6/24) in the 'intramuscular group' versus 64% (16/25) in the 'intratenosynovial group', that is, a difference of -39 percentage point (pp) (CI -65pp to -13pp), Fisher exact test p=0.001. Corresponding values for the 'intramuscular group' versus the 'intratenosynovial group' at 2 and 12 weeks were 21% (5/24) versus 48% (13/25), that is, a difference of -27pp (CI -53pp to -2pp), p=0.072 and 8% (2/24) versus 44% (11/25), that is, difference of -36pp (-58pp to -13pp), p=0.003. Most US, clinical and patient-reported scores improved more in the 'intratenosynovial group' at all follow-up visits. CONCLUSIONS: In this randomised double-blind clinical trial, patients with RA and tenosynovitis responded significantly better to US-guided intratenosynovial glucocorticoid injection than to intramuscular glucocorticoid injection, both at 4 and 12 weeks follow-up. TRIAL REGISTRATION NUMBER: EudraCT nr: 2013-003486-34. | |
| 27145822 | Antibodies to carbamylated α-enolase epitopes in rheumatoid arthritis also bind citrullin | 2016 May 4 | BACKGROUND: In addition to anti-citrullinated protein antibodies (ACPAs), antibodies targeting carbamylated (i.e., homocitrullinated) proteins (anti-CarP antibodies) have been described in rheumatoid arthritis (RA). However, the extent to which anti-CarP antibodies are truly distinct from ACPA remains unclear, and few studies have focused on specific autoantigens. Here, we examine cross-reactivity between ACPA and anti-CarP antibodies, in the context of the candidate autoantigen α-enolase. METHODS: Cross-reactivity was examined by immunoblotting of citrullinated and carbamylated proteins using purified ACPA; and by peptide absorption experiments, using the citrullinated α-enolase peptide CEP-1 and a homocitrulline-containing version (carb-CEP-1) in ELISA. The population-based case-control cohort EIRA (n = 2836 RA; 373 controls) was screened for reactivity with CEP-1 and carb-CEP-1, using the ISAC multiplex array. Associations between anti-CarP antibodies, smoking and genetic risk factors were analysed using unconditional logistic regression models. Differences in antibody levels were investigated using the Mann-Whitney U test. RESULTS: Affinity-purified ACPA was found to bind carbamylated proteins and homocitrulline-containing peptides, demonstrating definitive cross-reactivity between ACPA and anti-CarP antibodies. Anti-carb-CEP-1 reactivity in EIRA was almost exclusively confined to the CEP-1-positive subset, and this group of RA patients (21 %) displayed a particularly strong ACPA response with marked epitope spreading. The small RA subset (3 %) with homocitrulline reactivity in the absence of citrulline reactivity did not associate with smoking or risk genes, and importantly had significantly lower anti-carb-CEP-1 antibody levels. CONCLUSION: Our data presented herein cast doubt on the specificity of anti-CarP antibodies in RA, which we posit may be a subset of cross-reactive ACPA. | |
| 25292347 | Effect of anti-tumor necrosis factor alpha treatment of rheumatoid arthritis and chronic k | 2015 Apr | Although chronic kidney disease (CKD) may constitute a chronic inflammatory state indicated by elevated inflammatory mediators such as tumor necrosis factor alpha (TNF-α), the impact of anti-TNF-α therapy on progression of CKD in patients with rheumatoid arthritis (RA) is unclear. Seventy patients with RA and CKD were retrospectively analyzed. Outcomes were evaluated using the difference in the annual change of estimated glomerular filtration rate (eGFR) between patients treated with anti-TNF-α or without. Anti-TNF-α therapy significantly decreased disease activity score (DAS) 28 from 5.32 ± 0.78 to 3.59 ± 0.85 (p < 0.001). There was a tendency toward stabilization of eGFR after a mean of 2.9 ± 1.1 years from 50.3 ± 8.4 ml/min/1.73 m(2) to 54.5 ± 16.0 ml/min/1.73 m(2) in patients received anti-TNF-α therapy along with decreased DAS28 (p = 0.084). Conversely, eGFR decreased significantly in patients not receiving anti-TNF-α therapy after a mean of 2.8 ± 1.7 years from 52.6 ± 7.5 ml/min/1.73 m(2) to 46.5 ± 11.5 ml/min/1.73 m(2) (p = 0.041) without significant DAS28 change (p = 0.078). The annual change of eGFR was significantly different between patients treated with anti-TNF-α drugs and without (2.0 ± 7.0 ml/min/1.73 m(2)/year vs. -1.9 ± 4.0 ml/min/1.73 m(2)/year; difference in mean vs. -3.9 ± 7.3 ml/min/1.73 m(2)/year; p = 0.006). Use of anti-TNF-α drugs was significantly associated with positive annual change of eGFR in multivariate logistic regression analysis (p = 0.019). Among patients with RA and CKD, treatment with anti-TNF-α drugs was associated with less renal function decline. Anti-TNF-α drugs may be beneficial for managing RA combined with CKD. | |
| 27169300 | Rheumatoid Meningitis: Diagnostic and Therapeutic Observations. | 2016 Mar | A 75-year-old female with untreated rheumatoid arthritis presented with two weeks of behavioral changes and cognitive decline. A neurologic examination showed severe encephalopathy, brisk reflexes, and bilateral Babinski sign. A contrast-enhanced brain MRI demonstrated right meningeal enhancement and periventricular white matter disease. A computed tomographic angiogram (CTA) of the head and neck was negative for vasculitis. The cerebrospinal fluid (CSF) demonstrated lymphocytic pleocytosis. The patient's serum rheumatoid factor levels were elevated. A biopsy of the leptomeninges and cortex showed lymphocytic vasculitis of the cortical tissue and patchy lymphoplasmacytic infiltrates of dural small vessels consistent with rheumatoid meningitis. The patient received pulse-dose steroids followed by cyclophosphamide infusions. At her three month follow-up appointment, the patient's mental status had improved mildly. A follow-up brain MRI showed resolution of enhancement, but progression of subcortical bihemispheric white matter disease. Subsequently, the patient developed a respiratory infection and passed away. In rheumatoid arthritis, symptoms of encephalopathy, headaches, seizures, or focal neurologic deficits should raise suspicion for CNS involvement. This potentially treatable disease warrants prompt diagnosis. | |
| 26149185 | Comparative analysis of autoantibodies targeting peptidylarginine deiminase type 4, mutate | 2015 Nov | Antibodies against cyclic citrullinated peptides (anti-CCP) are widely used for diagnosis of rheumatoid arthritis (RA). We performed a comparative analysis of antibodies targeting the citrullinating enzyme peptidylarginine deiminase type 4 (anti-PAD4) and mutated citrullinated vimentin (anti-MCV) with anti-CCP autoantibodies in RA patients and examined their relationships with clinical parameters, cytokine profiles and the PADI4 gene. Autoantibodies were examined by enzyme-linked immunosorbent assay (ELISA) in sera of 170 RA patients and 103 controls. Cytokine profiles were measured using a multiplex system. PADI4 polymorphisms (89 G > A, 90 T > C and 92 G > C) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Anti-PAD4, anti-MCV and anti-CCP autoantibodies were detected in 24, 61 and 74% of RA patients, respectively. Positive correlations were observed between anti-PAD4 and disease duration; anti-CCP and erythrocyte sedimentation rate (ESR); anti-MCV and ESR and C-reactive protein. Anti-MCV antibodies were associated with high disease activity score 28 (DAS-28) in early RA. Concentrations of T helper type 1 (Th1) [tumour necrosis factor (TNF)-α, interleukin (IL)-12, IL-2, IL-1β], Th2 (IL-4, IL-6, IL-10, IL-13) and Th17 (IL-17) cytokines were higher in RA than in controls. Th2 and, to a lesser extent, Th1-related cytokines, showed positive correlations with anti-MCV and anti-CCP. The GTG haplotype in PADI4 was associated with anti-CCP and anti-MCV, but not anti-PAD4 antibodies. In conclusion, anti-PAD4 antibodies are detected mainly in established RA, which is in contrast to the early detection of antibodies against citrullinated peptide/proteins (ACPAs). Among autoantibodies, anti-MCV appear to perform better as markers of disease activity. Furthermore, anti-CCP and anti-MCV are associated genetically with the citrullinating enzyme PAD4 and are related strongly to Th1 and Th2 cytokines, suggesting a feed-forward loop between cytokines and ACPA production. | |
| 28110603 | Development of software and modification of Q-FISH protocol for estimation of individual t | 2017 Apr | Telomere length is an important indicator of proliferative cell history and potential. Decreasing telomere length in the cells of an immune system can indicate immune aging in immune-mediated and chronic inflammatory diseases. Quantitative fluorescent in situ hybridization (Q-FISH) of a labeled (C(3)TA[Formula: see text] peptide nucleic acid probe onto fixed metaphase cells followed by digital image microscopy allows the evaluation of telomere length in the arms of individual chromosomes. Computer-assisted analysis of microscopic images can provide quantitative information on the number of telomeric repeats in individual telomeres. We developed new software to estimate telomere length. The MeTeLen software contains new options that can be used to solve some Q-FISH and microscopy problems, including correction of irregular light effects and elimination of background fluorescence. The identification and description of chromosomes and chromosome regions are essential to the Q-FISH technique. To improve the quality of cytogenetic analysis after Q-FISH, we optimized the temperature and time of DNA-denaturation to get better DAPI-banding of metaphase chromosomes. MeTeLen was tested by comparing telomere length estimations for sister chromatids, background fluorescence estimations, and correction of nonuniform light effects. The application of the developed software for analysis of telomere length in patients with rheumatoid arthritis was demonstrated. |