Patients with AS had higher levels of OPN compared with controls. The plasma OPN level was correlated with serum ALP, OCN and CTX-I levels, but not with disease activity in AS. OPN might be involved in bone remodelling rather than in inflammation in AS.
Background Leucine-rich alpha2-glycoprotein (LRG) is a protein which contains leucine-rich repeats. Though physiologic functions of LRG have not been clearly defined, its expression was up-regulated during neutrophil differentiation and its levels were significantly elevated in some chronic inflammatory diseases such as inflammatory bowel disease. Objectives Our study aimed to investigate whether serum leucine-rich α2-glycoprotein (LRG) levels are elevated in patients with adult-onset Still's disease (AOSD) and determine their correlation with disease activity parameters. Methods We enrolled 39 patients with AOSD, 39 patients with rheumatoid arthritis (RA), and 39 controls. Forty-five serum samples from the patients with AOSD were assayed for LRG using enzyme-linked immunosorbent assay. Comprehensive AOSD activity was determined by modified Pouchot score. Results Serum LRG levels were significantly elevated in patients with AOSD (128.8±40.8 ng/mL) compared to those in patients with RA and in controls (35.9±15.7 ng/mL, p <0.001; 22.4±6.1 ng/mL, p <0.001, respectively). Patients with active AOSD had a significantly higher LRG level than those with inactive disease (141.4±31.3 ng/mL vs 79.8±37.1 ng/mL, p =0.002). Serum LRG levels were positively correlated with C-reactive protein (γ =0.387, p =0.015), lactate dehydrogenase (γ =0.370, p =0.026), and ferritin (γ =0.687, p <0.001) levels, and the modified Pouchot score (γ =0.756, p <0.001). Serum LRG levels decreased significantly after treatment in all 6 patients with active AOSD who had follow-up evaluations (p =0.007). The best cutoff value for LRG to distinguish AOSD from RA was 67.9 ng/mL, with a sensitivity of 92.3% and a specificity of 97.4%. Figure 1 Conclusions Serum LRG levels were increased in patients with AOSD and were well-correlated with disease activity measures. LRG may be a useful biomarker for distinguishing AOSD from RA and monitoring the disease activity of AOSD. References Takahashi N, Takahashi Y, Putnam FW. Periodicity of leucine and tandem repetition of a 24-amino acid segment in the primary structure of leucine-rich alpha 2-glycoprotein of human serum. Proc Natl Acad Sci U S A 1985;82:1906-10. Serada S, Fujimoto M, Terabe F, Iijima H, Shinzaki S, Matsuzaki S, et al. Serum leucine-rich alpha-2 glycoprotein is a disease activity biomarker in ulcerative colitis. Inflamm Bowel Dis 2012;18:2169-79. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.2855
BackgroundTakayasu arteritis (TAK) is systemic disease characterised by large vessel involvement. Although the vascular characteristics of TAK are well characterised, there is no well-organised study demonstrating the extravascular manifestations of TAK.ObjectivesTo evaluate the characteristics of extravascular manifestations of TAK, and to identify the association between vascular and extravascular manifestations of TAK.MethodsTAK patients from two independent cohorts who fulfilled the 1990 ACR classification and encoded M314 according to ICD-10 code between January 2012 and October 2017 were included in the study. Characteristics of the patients were retrospectively collected from the electronic dataset. A radiologist reviewed CT scans of all included patients to evaluate the pattern of vascular involvement and presence of sacroiliitis. Clinical findings including uveitis, skin lesion, oral ulcer, arthritis, and inflammatory bowel disease (IBD) were reviewed. Logistic regression analysis was performed to evaluate the association between vascular and extravascular manifestation.ResultsA total of 268 TAK patients were included. Mean age at diagnosis was 41.2±14.2 years and 236 (88.1%) were female. The most commonly involved vessel was common carotid artery (176 [65.7%]), and the most common type of vascular involvement was type V (120 [44.8%]). Extravascular manifestation of TAK was observed in 51 (19.0%) patients (table 1). The most common extravascular manifestation was arthritis (axial arthritis [sacroiliitis] [7.1%] and/or peripheral arthritis [6.0%]) (11.9%) followed by recurrent aphthous stomatitis (8.6%) and IBD (2.6%). In multivariable logistic regression analysis, the following factors were significantly associated with presence of arthritis (axial and/or peripheral arthritis): type IIB vascular involvement (adjusted OR 2.956, 95% CI 1.337–6.537, p=0.007) and erythrocyte sedimentation rate (ESR) (adjusted OR 1.014 95% CI 1.003–1.025, p=0.012).Abstract AB0689 – Table 1Extravascular manifestations of Takayasu arteritisn=268 Any extravascular manifestation51 (19.0%)Arthritis (axial arthritis [sacroiliitis] and/or peripheral arthritis)32 (11.9%)Recurrent aphthous stomatitis23 (8.6%)Inflammatory bowel disease7 (2.6%)Erythema nodosum4 (1.5%)Uveitis2 (0.7%)ConclusionsExtravascular manifestations of TAK are not rare and observed in up to one-fifth of patients. The most common extravascular manifestation was arthritis including sacroiliitis (11.9%). Type IIb vascular involvement pattern and high ESR were significantly associated with arthritis in TAK.AcknowledgementsNoneDisclosure of InterestNone declared
Background Proliferative lupus nephritis (Class III and IV) is the most severe form of lupus nephritis. The use of intravenous or oral prednisolone (PL) plus either intravenous cyclophosphamide or oral mycophenolate mofetil (MMF) currently is recommended as the standard induction therapy for proliferative lupus nephritis. However, despite improved outcomes with these induction therapies, end-stage renal disease still occurs in up to 30% of patients over a 20-year disease course. Thus, a new therapeutic modality is necessary. Thalidomide is a drug to treat multiple myeloma. Thalidomide can modulate NF-κB activity in myeloma cells, resulting in up-regulating pro-apoptotic regulators and down-regulating anti-apoptotic proteins. Recently, NF-κB was rediscovered to regulate mesangial proliferation in lupus-prone mice. Thus, considering the action-mechanism of thalidomide and its well-established efficacy in multiple myeloma, thalidomide could be an additional treatment for lupus nephritis, comparable to current regimes. Objectives We first investigated the efficacy of thalidomide on nephritis in lupus-prone mice and compared it to mycophenolate mofetil plus prednisolone. Methods Forty-three female NZB/WF1 mice were divided into eight groups (untreated; 1.7, 5, or 10 mg/kg of thalidomide alone; 1.7, 5, or 10 mg/kg of thalidomide plus prednisolone; and mycophenolate mofetilplus prednisolone). Proteinuria and histological damages were evaluated. Immune-complex deposition and nuclear translocation of NF-κB in kidney tissues were assessed by immunofluorescence staining. Serum concentration of anti-ds DNA and immunoglobulin G subclasses were also measured. Results In comparison with untreated mice, mice treated with 5 or 10 mg/kg of thalidomide plus prednisolone, or mycophenolate mofetilplus prednisoloneshowed a significant decrease in proteinuria and significantly lowered glomerular and tubular damage scores. Treatment with either 5 or 10 mg/kg of thalidomide plus prednisolone or mycophenolate mofetil plus prednisolone significantly decreased immune-complex accumulation, reduced the serum concentration of anti-ds-DNA, IgG2a, IgG2b and IgG3, and inhibited nuclear translocation of NF-κB in kidney tissues, compared to no treatment. Conclusions Thalidomide plus PL combination therapy significantly attenuated nephritis in lupus-prone mice. Thalidomide plus PL decreased the serum concentration of anti-ds DNA and IgG subclasses, and reduced glomerular deposition of immune complexes. Also they inhibited nuclear translocation of NF-kB and finally alleviated both proteinuria and histological renal damage. These data suggest that thalidomide plus PL might be anti-inflammatory in lupus nephritis pathophysiology and could serve as an additional therapy for lupus nephritis. Disclosure of Interest None Declared
BackgroundNucleotide-binding and oligomerization domain NOD-like receptors (NLRs) have been associated with several human diseases including infections, malignancies, and inflammatory disorders. These innate immune pattern recognition molecules paly critical roles in innate immunity and inflammation. Some inflammasome-forming NLRs including NLRP1, NLRP2, NLRP3, NLRC4, NLRC5, NLRP6, and NLRP7, can induce the activation of mitogen-activated protein kinase and the transcription factor NF-κB. A different set of NLRs, such as NLRP12, NLRX1, and NLRC3, negatively regulate diverse biological pathways associated with inflammation.ObjectivesThis study was performed to determine the expression pattern of NLRs in rheumatoid synovium and to investigate whether their regulation can influence the inflammatory response in fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA).MethodsWe explored the expression of several inflammasome-forming and -nonforming NLRs, including NLRP1, NLRP2, NLRP3, NLRC5, NLRX1, and NLRC3, in synovium obtained from patients with RA and patients with osteoarthritis (OA) by immunohistochemistry. The expression of NLRs was also studied in FLS derived from joint tissues of RA patients and OA patients using real time RT-PCR. RNA interference (RNAi) plasmids for NLRs were transfected to abrogate specific NLR expression in RA FLS, and adenovirus containing the NLR transcript was delivered into RA FLS to strengthen its gene expression. Levels of pro-inflammatory genes and their protein products were determined using real-time RT-PCR and ELISA in RA FLS.ResultsBy immunohistochemistry and real time RT-PCR, we were unable to distinguish RA from OA synovium on the basis of their level of RNA expression and protein production of NLRP2, NLRP3, NLRC5, and NLRX1. In synovial tissues from RA patients, NLRC1 was not detected, though RA FLS contained higher levels of NLRP1 compared to OA FLS. NLRC3 expression was detected at the RNA and protein levels in RA synovium and FLS, but its levels were much lowered that those from OA samples. Gene expression and production of IL-1β, IL-6, chemokine ligand 2 (CCL-2), CCL-7, cyclooxygenase 2 and MMP-9 were markedly increased in NLRC3 RNAi plasmid-transfected RA FLS, while transfection with adenoviral vectors encoding NLRC3 induced reductions in those levels.ConclusionsNLRC3 is down-regulated in RA synovium and the regulation of its expression showed anti-inflammatory activity in RA FLSs. These findings provide evidence for the anti-inflammatory effect of NLRC3 in RA.ReferencesWen H, Miao EA, Ting JP. Mechanisms of NOD-like receptor-associated inflammasome activation. Immunity 2013; 39: 432–41.Sidiropoulos PI, Goulielmos G, Voloudakis GK, Petraki E, Boumpas DT. Inflammasomes and rheumatic diseases: evolving concepts. Ann Rheum Dis 2008; 67: 1382-9.Schneider M, Zimmermann AG, Roberts RA, Zhang L, Swanson KV, Wen H, et al. The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription ...
BackgroundThe Red blood cell distribution (RDW) means the variability in the size of red blood cells. The RDW could predict the mortality in heart disease and sepsis. And recent reports showed associations between the RDW and disease activities in various autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Its mechanism is not yet clear, but one of hypothesis is that proinflammatory cytokine and oxidative stress could influence the maturation of red blood cells. It was often difficult to differentiate adult onset still's disease (AOSD) from sepsis in a febrile patient with leukocytosis, especially in early phase. Leukocytosis, elevated levels of the acute reactant proteins could not discriminate AOSD from sepsis, and only hyperferritinemia was helpful to distinguish the two diseases.ObjectivesWe investigated whether the RDW could be a differential marker for adult onset still's disease (AOSD) from sepsis in the early phase.MethodsWe retrospectively reviewed the medical records of 12 patients with AOSD, 28 patients with sepsis and 30 healthy controls. Laboratory data of patients were collected on the first day of hospitalization. All subjects in patient groups performed microbial tests to confirm or exclude sepsis. And data of healthy controls were collected one time at medical check-up visit.ResultsThe RDWs of patients with AOSD and sepsis were elevated than controls. There were no significant differences in white blood cell counts, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) between AOSD and sepsis group. However, the RDW of sepsis group was significantly elevated than that of AOSD group by Mann-Whitney's U analysis (p=0.042) as shown in Figure 1. Proportion of patients with abnormal RDW level (above 14.5%) in sepsis group (15/28 (53.5%)) was higher than in AOSD group (3/12 (25.0%)). However, the RDW was not a significant independent factor for discriminating sepsis from AOSD in the multivariate regression analysis.ConclusionsThe RDW was elevated in patients with AOSD and with sepsis. And it was elevated significantly higher in sepsis than in AOSD. So we suggest that the RDW might be a differential marker between AOSD and sepsis.ReferencesDabbah S, Hammerman H, Markiewicz W, et al. Relation between red cell distribution width and clinical outcomes after acute myocardial infarction. Am J Cardiol 2010;105:312-7.Jo YH, Kim KS, Lee JH, et al. Red cell distribution width is a prognostic factor in severe sepsis and septic shock. Am J Emer 2013;31:545-548Lee WS, Kim TY. Relation between red blood cell distribution width and inflammatory biomarkers in rheumatoid arthritis. Arch Pathol Lab Med 2010;134:505–6.Vaya A, Alis R, Hernandez JL, et al. RDW in patients with systemic lupus erythematosus. Influence of anaemia and inflammatory markers. Clin Hemorheol Microcirc 2013;54:333–9.Lippi G, Targher G, Montagnana M, et al. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med 2009;133:...
BackgroundInflammasomes are cytoplasmic multiprotein complexes that recognise various exogenous and endogenous danger signals in myeloid cells, particularly macrophages. Inflammasome activation eventually induces inflammatory responses in macrophages by activating gasdermin-d-mediated pyroptosis and the secretion of pro-inflammatory cytokines including interleukin (IL)−1β and IL-18 in a caspase-1-dependent manner. The production of IL-1 has been found to be highly induced in AS1 and caspase-1 level was significantly elevated in spondyloarthritis patients than in those with other arthritic diseases,2 suggesting the possibility that inflammasomes might be involved in pathogenesis of ankylosing spondylitis (AS). However, few studies have addressedd the roles of inflammasomes in AS.ObjectivesThis study was performed to investigate the role of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in the peripheral blood mononuclear cells (PBMCs) from AS patients.MethodsPBMCs from 11 patients and 9 healthy controls were isolated and mRNA expression levels of NLRP3 inflammasome, pro-IL-1β, IL-1β, pro-caspase-1, and caspase-1 were determined using quantitative real-time PCR. IL-17A (100 ng/mL) was added to the cell cultures, then, cytokine expression, signalling pathways, and inflammasome machinery are determined using real-time RT-PCR and Western blot. After transfection of siNLRP3 to AS PBMCs, mRNA and proteins levels of IL-1β and caspase-1 were determined using real time PCR and western blot.ResultsExpressions of NLRP3, IL-1β, and caspase-1 mRNAs, but not IL-18, were increased in PBMCs from AS patients compared to controls. Incubation of AS PBMCs with IL-17A significantly increased NLRP3, IL-1β, IL-18, and caspase-1 expressions in AS PBMCs. Western blot showed IL-17A treatment induced the phosphorylation of Akt, p38 MAPK, and NF-κB p65 in AS PBMCs. Down-regulation of NLRP3 by transfection of siRNA decreased mRNA expressions and productions of IL-1β and caspase-1 in AS PBMCs.ConclusionsActivity of NLRP3 inflammasome was increased in AS patients and IL-17A potentiated the activation of NLRP3 inflammasome. Our data suggest the possible role of NLRP3 inflammasome in inflammatory response in AS.References[1] Tan AL, Marzo-Ortega H, O’Connor P, Fraser A, Emery P, McGonagle D. Efficacy of anakinra in active ankylosing spondylitis: a clinical and magnetic resonance imaging study. Ann Rheum Dis. 2004;63:1041–1045.[2] Son CN, Bang SY, Kim JH, Choi CB, Kim TH, Jun JB. Caspase-1 level in synovial fluid is high in patients with spondyloarthropathy but not in patients with gout. J Korean Med Sci. 2013;28:1289–1292.Disclosure of InterestNone declared
BackgroundThe prognostic nutritional index (PNI), which was first introduced by Onodera et al., is calculated based on the serum albumin level and total lymphocyte count in the peripheral blood. It is proposed to be a parameter to reflect immunonutritional status, however, it is also known that albumin and lymphocyte count may decrease in proportion to inflammatory burdens in autoimmune diseases.ObjectivesWe investigated whether PNI at diagnosis can be used for estimating BVAS at diagnosis in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) patients.MethodsWe retrospectively reviewed the medical records of 160 patients with AAV. We calculated Birmingham vasculitis activity score (BVAS). We collected laboratory results including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), while blood cell, lymphocyte and platelet counts and serum albumin. Prognostic nutritional index (PNI) was calculated by (10 x serum albumin (g/dl)+0.005 x lymphocyte count (/mm3)). The association was assessed linear regression analyses. The optimal cut-off of PNI for predicting relapse was set at 36.6. Comparison of cumulative relapse free survival was analysed by the Kaplan-Meier survival analysis.ResultsThe mean age at diagnosis was 55.2 years and 48 patients were male. Eighty-five patients had MPA, 41 patients had GPA and 34 patients had EGPA. The mean BVAS and PNI at diagnosis were 11.9 and 43.4. Forty-three patients experienced relapse of AAV. In univariable linear regression analysis, BVAS was positively correlated with ESR and CRP and was negatively correlated with lymphocyte count, serum albumin level and PNI. In multivariable analysis, BVAS was the most significantly associated with only PNI (standardised β=−0.296). Patients having PNI at diagnosis ≤36.6 exhibited significantly lower cumulative relapse free survival rate than those having PNI at diagnosis >36.6 (p=0.002).Abstract SAT0547 – Table 3Univariable linear regression analysis of BVAS and continuous variables in 160 patients with AAVUnivariable analysis RegressionCoefficient(Crude B)CorrelationCoefficient(R=β)p value Demographic data at diagnosis Age (year old)0.0270.0530.504Acute reactants at diagnosis ESR (mm/hr)0.0440.2180.006 CRP (mg/L)0.0230.1690.033Laboratory results reflecting inflammation at diagnosis White blood cell count (/mm3)0.0000.1040.189 Lymphocyte count (/mm3)−0.002−0.2140.007 Platelet count (x1,000/mm3)0.0030.0600.449 Serum albumin (g/dL)−2.557−0.2620.001PNI−0.252−0.307<0.001BVAS: Birmingham vasculitis activity score; ANCA: antineutrophil cytoplasmic antibody; AAV: ANCA associated vasculitis; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; PNI: prognostic nutritional index.Abstract SAT0547 – Figure 2The association of PNI at diagnosis with relapse of AAV during the follow-up. We selected the optimal cut-off of PNI at 36.6, divided patients into two groups according to the cut-off and conducted Kaplan-Meier survival analysis. Patients having PNI at diagnosis ≤36.6 exhibited significantly lower cumulative re...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.