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ID PMID Title PublicationDate abstract
29939313 Rasch measurement in rheumatoid arthritis: deriving psychometrically optimal measures from 2018 Oct 1 OBJECTIVE: Recently we developed the Rasch Everyday Activity Limitations (REAL) generic item bank for measuring physical function. In this study we evaluate the REAL item bank in 209 RA patients and demonstrate how computerized adaptive testing (CAT) and Optimal Test Assembly methods can be used to derive measures from the REAL item bank with superior measurement performance compared with the HAQ Disability Index (HAQ-DI). METHODS: Structural validity of the item bank was assessed using confirmatory factor analysis. The validity of the REAL score metric in RA was evaluated by examining differential item functioning against the general population calibration sample. Besides the REAL-CAT, a 6-item short form (REAL-6) was developed using Optimal Test Assembly that was optimized with respect to common disability levels in RA, content and reading ease. Measurement precision of the different instruments was examined using item response theory methods. Construct validity was evaluated by testing hypothesized correlations with external measures. RESULTS: Good model-data fit was observed for a one-dimensional model and only two items showed differential item functioning of substantial magnitude. The REAL-CAT had superior measurement precision compared with HAQ-DI and REAL-6. REAL-6 outperformed HAQ-DI across all but the very lowest level of physical function. All three instruments demonstrated good construct validity (>75% of hypotheses affirmed) and only HAQ-DI had a ceiling effect (23.9%). CONCLUSION: This study supports the validity of the REAL item bank and illustrates the potential of CAT and OTA applications based on the REAL item bank for assessing physical function in RA.
29791587 Association study of AFF1 rs340630 polymorphism with genetic susceptibility to rheumatoid 2018 This study was performed to examine whether the AF4/FMR2 family, member 1 (AFF1) rs340630 polymorphism is involved in the genetic background of rheumatoid arthritis (RA) in a Chinese population. Two different study groups of RA patients and controls (328 RA patients and 449 healthy controls in the first study group; 232 RA patients and 313 controls in the second study group) were included in our study. Overall, there was no significant difference in either genotype (P=0.71 and 0.64 in the first and second study group, respectively) nor allele (in the first study group: A vs G, P=0.65, OR=1.05, 95%CI=0.85-1.29; in the second study group: G vs A, P=0.47, OR=1.10, 95%CI=0.86-1.40) frequencies of AFF1 rs340630 polymorphism between RA patients and controls. Our study represents the first report assessing the association of AFF1 rs340630 polymorphism with RA risk. No significant evidence was found for the dominant or recessive models. Further case-control studies with larger sample sizes and fine-mapping studies are needed to clarify the role of AFF1 in the genetic basis of RA.
29939099 Combination effect of anti-rheumatic medications for coronary artery diseases risk in rheu 2019 Feb OBJECTIVES: To determine whether a combination of anti-rheumatic drugs is associated with the risk of coronary artery diseases (CAD) in incident rheumatoid arthritis (RA) patients. METHODS: This population-based cohort study used administrative data to identify 6260 newly-diagnosed patients with RA (age ≥20 years) as the study group. The study end-point was occurrence of CAD according to the ICD-9-CM codes. Exposure to different combinations of drugs and the risk of CAD was assessed. These included different combinatiosn of celecoxib (Cx), hydroxychloroquine (HCQ), methotrexate (MTX), and sulfasalazine (SSZ). Patients who never used Cx, HCQ, MTX, or SSZ were used as a reference group. A Cox proportional hazards model was used to estimate the hazard ratio (HR) of disease after controlling for demographic and other co-morbidities. When the proportionality assumption was violated, the spline curve of the Scaled Schoenfeld residuals was fitted to demonstrate the estimated effect on CAD over time for drug usage. RESULTS: Among RA patients, the adjusted HR (95% confidence interval) of CAD for "Cx only", "Cx and HCQ ever", and "Cx, HCQ, MTX, and SSZ ever", were 0.29 (0.19-0.44), 0.46 (0.24-0.88), and 0.42 (0.24- 0.75), respectively, during the first period of 0-3, 4, or 7 years. However, they became 1.04 (0.78-1.38), 1.16 (0.62-2.19), and 0.59 (0.32-1.08), respectively, during the second time period of 3, 4, or 7-10 years. The adjusted HR (95% CI) of CAD for "Cx, MTX, and SSZ ever" remains constant at 0.12 (0.02-0.89). CONCLUSIONS: Celecoxib-DMARDs drug combinations were associated with reduced CAD risk on incident RA patients, and some of them exhibited the time-varying drug effect.
29104161 Risk of Incident Liver Disease in Patients with Psoriasis, Psoriatic Arthritis, and Rheuma 2018 Apr Relatively little is known about the risk for incident liver disease in psoriasis (PsO), psoriatic arthritis (PsA), and rheumatoid arthritis (RA). We performed a cohort study among patients with PsO, PsA, or RA and matched controls in The Health Improvement Network from 1994 to 2014. Outcomes of interest were any liver disease, nonalcoholic fatty liver disease, and cirrhosis (any etiology). Among patients with PsO (N = 197,130), PsA (N = 12,308), RA (N = 54,251), and matched controls (N = 1,279,754), the adjusted hazard ratios for any liver disease were elevated among patients with PsO (without systemic therapy [ST] 1.37; with ST 1.97), PsA (without ST 1.38; with ST 1.67), and RA without an ST (1.49) but not elevated in patients with RA prescribed an ST (0.96). Incident nonalcoholic fatty liver disease was highest in patients with PsO prescribed an ST (2.23) and PsA with an ST (2.11). The risk of cirrhosis was highest among patients with PsO with an ST (2.62) and PsA without an ST (3.15). Additionally, the prevalence of liver disease and cirrhosis increased in a stepwise fashion with increasing body surface area affected by PsO (P for trend <0.001). More so than RA, PsO and PsA are associated with liver disease, particularly nonalcoholic fatty liver disease and cirrhosis, and this was true even among patients without ST exposure.
29381842 Increased Circulating Follicular Treg Cells Are Associated With Lower Levels of Autoantibo 2018 May OBJECTIVE: To examine the expression and changes in function of circulating CD4+CXCR5+FoxP3+ follicular Treg (Tfr) cells in patients with active rheumatoid arthritis (RA) and in patients with RA in stable remission, and to clarify the role of Tfr cells in the pathogenesis of RA. METHODS: Levels of Tfr cells and follicular helper T (Tfh) cells in the peripheral blood of 39 patients with active RA, 39 patients with RA in stable remission, and 33 healthy controls were detected by flow cytometry. The function of Tfr cells was measured by coculturing them with Tfh cells and B cells. Activated CD45RA-FoxP3(high) Tfr cells were also analyzed. Clinical indicators, including serum Ig and autoantibody levels, were tested, and correlations with Tfr cells were systematically analyzed. The Disease Activity Score in 28 joints (DAS28) was calculated, and correlation analysis with Tfr cells was conducted. RESULTS: The level of CD4+CXCR5+FoxP3+ Tfr cells and the Tfr cell:Tfh cell ratio in peripheral blood from patients with RA in stable remission were significantly increased compared with the same measures in patients with active RA and in healthy controls. The function of Tfr cells was enhanced, and the activated CD45RA-FoxP3(high) Tfr cell subset was increased in patients with RA in stable remission compared with healthy controls. Furthermore, the number of Tfr cells in RA patients was inversely correlated with IgG, rheumatoid factor, and anti-cyclic citrullinated peptide as well as with the DAS28. CONCLUSION: Circulating Tfr cells are increased as patients with RA achieve stable remission of disease, and increased Tfr cells can suppress autoimmunity in RA patients to stabilize their condition. Our results provide novel insight into RA pathogenesis.
30312697 The non-enzymatic glycation of LDL proteins results in biochemical alterations - A correla 2019 Feb 1 Advanced glycation end-products (AGEs) can aggregate amid incessant inflammation, as may be available in patients with rheumatoid arthritis. d-Ribose reacts more promptly than glucose monosaccharide to the proteins and forms heterogeneous group of products known as AGEs. Obesity includes persons with provocative joint inflammation with increased lipid profile. Immunogenic evidences recommend a cross-sectional relationship between glycated LDL-Apo B100 and inflammation. The point of this examination was to look at the connection between d-ribose glycated ApoB100 (ApoB100-AGE) with obesity and rheumatoid arthritis. The binding specificity of auto-antibodies against ApoB100-AGE antigen present in obesity and rheumatoid arthritis patient's serum were inspected by direct binding and was further established by competitive inhibition ELISA. In the present study, hydroxyl radical, superoxide radical, ketoamine moieties, hydroxyl-methyl furfural (HMF) and carbonyl substances were evaluated in the patients' serum via respective specific methods. The prevalence of auto-antibodies against ApoB100-AGE antigen was recorded to be 58% and 52.86% from obese and rheumatoid arthritis patient respectively in contrast to its native analogue (P < 0.001). Moreover, the autoantibodies present in obese and arthritis patients were found to be highly specific towards ApoB100-AGE as confirmed by inhibition ELISA.
30231487 lncRNA NTT/PBOV1 Axis Promotes Monocyte Differentiation and Is Elevated in Rheumatoid Arth 2018 Sep 18 Monocytes/macrophages are important in orchestrating inflammatory responses. However, knowledge of the long noncoding RNA (lncRNA) regulation of monocytic cell differentiation and diseases remains limited. We aimed to elucidate the role of the 17 kb lncRNA noncoding transcript in T cells (NTT) in monocyte functions. Knockdown and chromatin immunoprecipitation (ChIP) assays in THP-1 cells (human monocytic leukemia cell line) revealed that NTT is regulated by the monocyte key transcription factor C/EBPβ and that it binds to the promoter of nearby gene PBOV1 via hnRNP-U. Overexpression of PBOV1 in THP-1 cells resulted in cell cycle G1 arrest, differentiation into macrophages, a marked increase in IL-10 and CXCL10 mRNA levels, and upregulation of the costimulatory molecules. In contrast to the downregulated NTT observed in lipopolysaccharide (LPS)-treated THP-1 cells, the C/EBPβ/NTT/PBOV1 axis was found to be hyperactivated in peripheral blood mononuclear cells (PBMCs) of first-time diagnosed untreated early rheumatoid arthritis (RA) patients, and their gene expression levels decreased markedly after treatment. Higher initial C/EBPβ/NTT/PBOV1 expression levels were associated with a trend of higher disease activity DAS28 scores. In conclusion, our study suggests that the lncRNA NTT is a regulator of inflammation in monocytes, and its activation participates in monocyte/macrophage differentiation and the pathogenesis of RA.
30051736 Living With Rheumatoid Arthritis in Spain: A Qualitative Study of Patient Experience and t 2020 Nov The aim of this study was to explore the experience of Spanish people living with rheumatoid arthritis (RA) and the support these people received from health professionals, particularly nurses. Nineteen patients with >1 year diagnosis, disease activity moderate or severe (DAS28 > 3.2), and already treated with disease-modifying antirheumatic drugs (DMARDs) were interviewed. A thematic analysis was performed to interpret the discourses. The difficulties of symptom management; the need for home-adaptations, the difficulties of living with a deteriorating self-image; and the reluctant reliance on medication to control their disease were the main themes that emerged from the discourse analysis of this study. Nurses appeared to have a limited role in RA patients care, and focused primarily on giving information and training for biological therapies. RA patients in Spain would benefit from having contact with specialist nurses who could empower them to self-manage their disease, as happens in other countries.
30562766 [Increased receptor activator of nuclear factor kappa B ligand expressed on B10 cells in r 2018 Dec 18 OBJECTIVE: To detect receptor activator of nuclear factor kappa B ligand (RANKL) expressed on B10 cells in rheumatoid arthritis (RA) and to evaluate the correlation between RANKL-producing B10 cells in RA and clinical features and laboratory parameters, trying to reveal the possible role of B10 cells in the pathogenesis of RA and the potential mechanism of impaired immunosuppressive capacities. METHODS: 25 RA patients and 20 healthy volunteers were enrolled. These RA patients did not received treatment with glucocorticoids, disease-modifying anti-rheumatic drug and biologics during the recent half of a year. The levels of RANKL-producing B10 cells were measured by flow cytometry (FCM) and polymerase chain reaction (PCR). The correlation between the frequencies of RANKL-producing B10 cells in RA and clinical data, laboratory parameters were analyzed. The role of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) in inducing RANKL expression in B10 cells was evaluated by in vitro stimulation assay. Independent samples t test, Pearson and Spearman correlation were used for statistical analysis. RESULTS: B10 cells were capable of producing RANKL at a low level in health controls. The frequencies of RANKL-producing B10 cells were markedly higher in RA patients than in health controls (3.65%±1.59% vs. 2.25%±0.68%, P<0.01). The frequencies of these cells correlated positively with RA tender joint counts, swollen joint counts and disease activity score in 28 joints (DAS28) (r=0.479, P=0.035; r=0.519, P=0.008; r=0.526, P=0.019). However, no correlation was found between these cells and RA patient age, disease duration, or the levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA). After in vitro stimulation by TNF-α, but not IL-1β, B10 cells isolated from healthy donors demonstrated fundamentally upregulated expression of RANKL. CONCLUSION: Our studies showed the frequencies of RANKL-producing B10 cells were markedly higher in RA patients, and their frequencies were positively correlated with RA tender joint counts, swollen joint counts and DAS28. These findings suggested that B10 cells might be involved in RA bone destruction.
29744570 Alopecia universalis in a patient with rheumatoid arthritis developed during treatment wi 2018 Jun Alopecia universalis is an advanced form of alopecia areata, characterized by complete loss of hair on all hair-bearing areas. It is currently believed to be an autoimmune disorder. The development of alopecia during treatment with tumor necrosis factor alpha (TNF-α) inhibitors is a rarely observed adverse event. This case describes a 56-year-old female patient with rheumatoid arthritis (RA), who developed alopecia universalis during treatment with adalimumab. There was no improvement in alopecia despite withdrawal of adalimumab. It is believed that interferon-α is the main cytokine involved in promoting inflammation in hair loss after blocking TNF-α by TNF inhibitors. Risk/benefit ratio of maintenance and discontinuation of the drug should be weighed up when alopecia appears during treatment with TNF inhibitors.
29042358 Safety, immunogenicity and efficacy after switching from reference infliximab to biosimila 2018 Feb OBJECTIVES: Efficacy, safety and immunogenicity results from the phase III study of SB2, a biosimilar of reference infliximab (INF), were previously reported through 54 weeks. This transition period compared results in patients with rheumatoid arthritis (RA) who switched from INF to SB2 with those in patients who maintained treatment with INF or SB2. METHODS: Patients with moderate to severe RA despite methotrexate treatment were randomised (1:1) to receive SB2 or INF at weeks 0, 2 and 6 and every 8 weeks thereafter until week 46. At week 54, patients previously receiving INF were rerandomised (1:1) to switch to SB2 (INF/SB2 (n=94)) or to continue on INF (INF/INF (n=101)) up to week 70. Patients previously receiving SB2 continued on SB2 (SB2/SB2 (n=201)) up to week 70. Efficacy, safety and immunogenicity were assessed up to week 78. RESULTS: Efficacy was sustained and comparable across treatment groups. American College of Rheumatology (ACR) 20 responses between weeks 54 and 78 ranged from 63.5% to 72.3% with INF/SB2, 66.3%%-69.4% with INF/INF and 65.6%-68.3% with SB2/SB2. Treatment-emergent adverse events during this time occurred in 36.2%, 35.6% and 40.3%, respectively, and infusion-related reactions in 3.2%, 2.0% and 3.5%. Among patients who were negative for antidrug antibodies (ADA) up to week 54, newly developed ADAs were reported in 14.6%, 14.9% and 14.1% of the INF/SB2, INF/INF and SB2/SB2 groups, respectively. CONCLUSIONS: The efficacy, safety and immunogenicity profiles remained comparable among the INF/SB2, INF/INF and SB2/SB2 groups up to week 78, with no treatment-emergent issues or clinically relevant immunogenicity after switching from INF to SB2. TRIAL REGISTRATION NUMBER: NCT01936181; EudraCT number: 2012-005733-37.
29574518 Effects of once-monthly minodronate versus risedronate in osteoporosis patients with rheum 2018 Jul A head-to-head comparison of once-monthly oral bisphosphonates minodronate (MIN) and risedronate (RIS) in patients with rheumatoid arthritis (RA) demonstrated that MIN has the same effect as RIS on increase in bone mineral density (BMD) and a stronger effect on inhibition of bone resorption than RIS, suggesting that MIN is a promising treatment option for osteoporosis patients with RA. INTRODUCTION: To evaluate the effect of once-monthly oral MIN in patients with RA, a prospective, randomized, open-label, head-to-head comparison with once-monthly oral RIS was conducted. METHODS: A total of 83 patients with RA were randomly assigned to either once-monthly oral MIN 50 mg (n = 42) or once-monthly oral RIS 75 mg (n = 41). Serial BMD and bone turnover markers were measured and compared between the treatment groups. RESULTS: BMD (lumbar spine, total hip, femoral neck) increased significantly after 12 months of treatment with MIN (3.8, 2.0, and 2.2%, respectively, P < 0.05) and RIS (3.6, 1.9, and 1.9%, respectively, P < 0.05). There were no significant differences between the treatment groups. Percent changes of bone turnover markers from baseline to 12 months in the MIN group were significantly greater than those in the RIS group (TRACP-5b: - 36.3 vs - 19.3%, P < 0.05; NTX: - 27.1 vs - 17.3%, P < 0.05; BAP: -30.2 vs -19.4%, P < 0.05). CONCLUSIONS: The present study of RA patients demonstrated that MIN has the same effect as RIS on increase in BMD and a stronger effect on inhibition of bone resorption than RIS. The results suggest that MIN is a promising treatment option for osteoporosis patients with RA.
30118518 Association of high titers of anti-carbamylated protein antibodies with decreased bone min 2018 Rheumatoid arthritis (RA) has a negative impact on bone that is partly mediated by anti-citrullinated proteins antibodies (ACPA). These antibodies are associated with erosions, and with juxta-articular and systemic bone loss. Other RA autoantibodies, the anti-carbamylated protein antibodies (anti-CarPA), are independently associated with erosions. However, we do not know if they are also associated with juxta-articular and systemic bone loss. Here, we have addressed this question with data from 548 early arthritis (EA) patients. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar spine (LS), total hip (TH) and metacarpophalangeal joints (MCP). The 25.9% anti-CarPA positive patients did not show significant differences in BMD Z-scores with the negative patients. Nevertheless, this result was due to the similarity between negative and low-positive (below the median of the positive) patients, whereas the high-positive patients showed significant decrease of BMD at LS (β = -0.39, p = 0.01) and TH (β = -0.30, p = 0.02); but not at the juxta-articular bone of MCP. Given the overlap between anti-CarPA and ACPA, we included the two autoantibodies in an analysis that showed significantly lower BMD Z-scores at LS and TH (p< 0.01) only in the ACPA positive/anti-CarPA high-positive subgroup. However, the similar coefficients of regression between the ACPA positive/anti-CarPA high-positive and the ACPA negative/anti-CarPA high-positive subgroups (β = -0.50 vs. -0.52 at LS, and β = -0.37 vs. -0.30 at TH) suggested an independent association. Overall, these results support a contribution of anti-CarPA to systemic bone loss in EA patients.
29392593 Gastrointestinal Perforations with Biologics in Patients with Rheumatoid Arthritis: Implic 2018 Jun Gastrointestinal (GI) perforations are rare events in rheumatoid arthritis (RA) patients, but cause significant morbidity and mortality. Several studies indicate that RA patients may be at higher risk of GI perforation. Traditional RA treatments such as glucocorticoids and non-steroidal anti-inflammatory drugs increase the risk of perforation. In the past two decades, a new class of therapeutic agents called biologics has been added to the RA treatment armamentarium. Biologics are effective in controlling disease activity and are generally well tolerated; however, reports of GI perforations in association with biologics have arisen. In particular, drugs that inhibit the interleukin (IL)-6 cytokine receptor have demonstrated a higher risk of perforation compared with other therapies. Recent reports also suggest that janus kinase inhibitors may increase the risk of perforation, perhaps via downstream effects on IL-6 signaling. In this review, we discuss current data on the risk of GI perforations among RA patients receiving targeted therapies and its clinical relevance.
28882619 Variable domain glycosylation of ACPA-IgG: A missing link in the maturation of the ACPA re 2018 Jan Anti-citrullinated Protein Antibodies (ACPA) are excellent markers for Rheumatoid arthritis (RA) and are postulated to have a pathogenic role in the disease process. A multistep model for the evolution of the ACPA response in RA was proposed in which an initial break of tolerance causes, as "first hit", "silent" production of ACPA without any clinical symptoms. The model further proposes that the ACPA immune response matures upon a certain (unknown) trigger, a "second hit", which leads to epitope spreading, an increase in ACPA titres and extended isotype usage before clinical RA manifestations. These occurrences are indicative of an expansion of the citrulline-specific B cell response, though ACPA remain of low avidity even in established disease. This persistence of low avidity is puzzling, as the typical signs of maturation of the immune response seem to be uncoupled from the classical process of affinity maturation. In fact, it suggests that B cells expressing ACPA could bypass selection mechanisms that otherwise control the expansion of auto-reactive B cells. In the established, chronic phase, we recently found that ACPA-IgG are extensively glycosylated in the variable (Fab) domain. More than 90% of ACPA-IgG molecules carry Fab glycans that are highly sialylated. This molecular feature is striking and may provide a missing link in our understanding of the maturation of the ACPA immune response. This review, therefore, describes the current knowledge about ACPA Fab glycosylation in the pathogenesis of RA.
30415451 Patient-reported outcomes with golimumab in patients with rheumatoid arthritis, psoriatic 2019 Jan The TNF inhibitor golimumab (GLM) is a treatment option in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). The GO-NICE study assessed patient-reported outcomes (PRO) in patients newly treated with monthly GLM 50 mg subcutaneously (SC) under real-life conditions in Germany. A prospective non-interventional study with 24-month observation per patient was conducted at 158 sites. Available for analysis were 1,458 patients, 474 with rheumatoid arthritis (RA: 54.9 ± 13.4 years, 72.8% females, 60.4% biologic-naïve), 501 with psoriatic arthritis (PsA: 50.5 ± 12.1 years, 54.1% females; 47.5% biologic-naïve), and 483 with ankylosing spondylitis (AS: 43.6 ± 12.3 years, 66.5% males; 58.4% biologic-naïve). A total of 664 patients completed follow-up to month 24. An improvement of QoL by EuroQoL EQ-5D-3L was seen after 6 months and was maintained over 24 months. The patients' health state today (EQ visual analog scale) improved statistically significantly (p < 0.0001 vs. BL) from 51.0 at baseline (BL) to 63.4 (RA), from 48.4 to 64.3 (PsA) and from 46.8 to 66.5 (AS). Functional ability (FFbH) improved significantly (p < 0.003 vs. BL) from BL 68.2 to 76.1 points (RA), from 69.0 to 76.8 points (PsA), and from 69.0 to 78.5 points (AS). The mean FACIT-Fatigue score increased significantly (p < 0.0001 vs. BL) from BL 32.4 to 38.3 points (RA), from 30.0 to 35.9 points (PsA), and from 29.9 to 37.9 points after 24 months (AS); p < 0.0001 vs. BL each. On treatment with GLM SC once monthly, significant improvements in patient-reported QoL parameters were noted in a very similar manner in all three diseases.Trial registration ClinTrials.gov Identifier: NCT01313858. Registered March 14, 2011; https://clinicaltrials.gov/ct2/show/record/NCT01313858 .
30443790 Sclerostin rather than Dickkopf-1 is associated with mSASSS but not with disease activity 2019 Apr OBJECTIVE: To determine the serum levels of Dickkopf-1 (DKK-1) and sclerostin, as well as their correlations with the structural damage assessed by modified stoke ankylosing spondylitis spine score (mSASSS) and the disease activity evaluated by ankylosing spondylitis disease activity score (ASDAS) in patients with ankylosing spondylitis (AS). METHODS: Eighty-eight AS patients, 26 rheumatoid arthritis (RA) patients, and 26 age- and gender-matched healthy controls (HC) were collected from rheumatic clinic of the Second Affiliated Hospital of Zhejiang University, School of Medicine, between March 2015 and July 2015. Demographic data, parameters of ASDAS, and image evaluations of spine (i.e., mSASSS) were collected. The serum levels of DKK-1 and sclerostin were measured using commercially available ELISA kits. RESULTS: Both DKK-1 and sclerostin were significantly higher in the AS patients than in the controls (1855 ± 84.58 vs. 1406 ± 99.76 pg/ml and 106 ± 6.75 vs. 62.78 ± 6.39 pmol/l, respectively, P < 0.05). The correlation analysis suggested a negative correlation between serum sclerostin and mSASSS (P = 0.019, r(2) = 0.062). DKK-1 had a trend of positive correlation with mSASSS, but was not statistically significant (P > 0.05). There was no association between the serum levels of DKK-1 or sclerostin and disease activity assessed by ASDAS (P > 0.05). DKK-1 and sclerostin had a negative correlation (P = 0.013, r(2) = 0.07). CONCLUSION: In the present study, the expressions of serum DKK-1 and sclerostin were independent of disease activity. Sclerostin was negatively correlated with the mSASSS, which suggests that sclerostin may be a potential marker indicating the spine ossification process in AS. The specific mechanism remains to be investigated.
30161253 Relative efficiencies of peptidylarginine deiminase 2 and 4 in generating target sites for 2018 OBJECTIVE: Peptidylarginine deiminase 2 (PAD2) and PAD4 are expressed in the synovium of rheumatoid arthritis (RA) patients and catalyze citrullination of arginine residues in proteins targeted by anti-citrullinated protein antibodies (ACPAs). Little is known about the relative importance of PAD2 and PAD4 in generating citrullinated self-antigens. Here we investigate the ability of PAD2 and PAD4 to generate citrullinated targets for ACPAs in four human proteins. METHODS: Synovial fluid (SF) and plasma were collected from 42 RA patients. Human fibrinogen, human alpha-enolase (ENO1), human histone H3, and human serum albumin (HSA) were citrullinated in vitro by PAD2 or PAD4. The total degree of citrullination was determined using the anti-modified citrulline approach. Antibody binding to native and citrullinated proteins was measured by ELISA. RESULTS: ACPAs within pooled SF from multiple RA patients reacted equally well with, and cross-reacted with, PAD2- and PAD4-citrullinated fibrinogen. ACPAs from most individual patient SF and plasma samples bound equally well to PAD2- and PAD4-citrullinated fibrinogen or ENO1. When histone H3 was used as target, PAD4 was generally superior in generating epitopes recognized by ACPAs. No binding to citrullinated HSA was observed. CONCLUSION: In most patients, PAD2 and PAD4 are equally efficient in generating citrullinated target sites for ACPAs in fibrinogen and ENO1. The binding of autoantibodies to histone H3 was generally higher after citrullination with PAD4 than with PAD2. Citrullinated HSA is not a target for ACPAs.
30112359 Apoptotic and Anti-Inflammatory Effects of Eupatorium japonicum Thunb. in Rheumatoid Arthr 2018 Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovitis, hyperplasia, and the destruction of bone and cartilage. A variety of immunosuppressive biological agents have been developed because the pathogenesis of RA is related predominantly to the inflammatory response. However, rheumatoid arthritis fibroblast-like synovial cells (RAFLS), which are known to play an important role in RA progression, exhibit resistance to immunosuppressants through cancer-like properties. In this study, we identified a novel therapeutic compound for RA, which reduced inflammation and the abnormal proliferation of RAFLS in natural product library made from Korean native plants. Eupatorium japonicum Thunb. (EJT) extract, a component of the natural product library, most effectively reduced viability through the induction of ROS-mediated apoptosis in a dose-dependent manner. In addition, the increased ROS induced the expression of ATF4 and CHOP, key players in ER stress-mediated apoptosis. Interestingly, EJT extract treatment dose-dependently reduced the expression of IL-1β and the transcription of MMP-9, which were induced by TNF-α treatment, through the inhibition of NF-κB and p38 activation. Collectively, we found that EJT extract exerted apoptotic effects through increases in ROS production and CHOP expression and exerted anti-inflammatory effects through the suppression of NF-κB activation, IL-1β expression, and MMP-9 transcription.
28261976 Prevalence of co-morbidities and evaluation of their monitoring in Korean patients with rh 2018 Jul AIM: We designed this study to evaluate the prevalence of comorbidities, their monitoring states and association with treatment medication in Korean rheumatoid arthritis (RA) patients compared with patients from other countries. METHODS: We analyzed 1050 RA patients from 11 Korean centers and compared them with 3520 patients from 16 other countries using an international, cross-sectional study evaluating comorbidities of RA (COMORA) database. RESULTS: Annual evaluations of cardiovascular (CV) risk were less frequently performed in Korea (P = 0.0011). The prevalence of CV-associated morbidity was similar between Korean and international RA patients, although the proportions of current smokers, patients with a family history of CV disease, patients with hyperlipidemia, and patients with Framingham score > 20% were significantly lower in Korea (P < 0.0001 for all), and the antiplatelet agents were more optimally used in Korea (P = 0.0004). Prostate cancer screening was less frequently performed compared to other countries (P < 0.0001). Less than 10% of Korean RA patients were given influenza and pneumococcal vaccinations according to current recommendations. CONCLUSIONS: There are differences in the prevalence of comorbidities and monitoring states of the risk factors between patients in Korea and in other countries. The prevalence of CV morbidity was similar between the two groups although the prevalence of CV risk factors was significantly low in Korea, suggesting that rheumatologists in Korea need to pay more attention to yearly CV risk monitoring, in addition to the screening of malignancy and vaccination of RA patients against infectious diseases.