The study was undertaken to evaluate clinical and laboratory characteristics of patients with lupus enteritis and to investigate its association with anti-endothelial cell antibodies (AECAs). Systemic lupus erythematosus (SLE) patients who were admitted to Kangnam St. Mary's Hospital with complaints of acute abdominal pain from January 1990 to July 2006 were reviewed retrospectively. The clinical features, laboratory data and prognosis of these patients were analyzed. Among the 706 SLE patients admitted during the study period, 87 were found to admit for acute abdominal pain. Among them, 41 patients were identified with lupus enteritis. The SLE disease activity index score at admission and the mean prednisolone dose administered during the last three months prior to admission were significantly higher in patients with lupus enteritis than those with other causes (P < 0.001, P = 0.036). Serum anti-endothelial cell antibody (AECA-IgG) titer was also significantly higher in patients with lupus enteritis than those with other manifestations or healthy controls (P = 0.040, P < 0.001). Four out of 13 recurrent patients had pre-existing anti-phospholipid syndrome (APS), whereas only one out of 28 non-recurrent patients had pre-existing APS (P = 0.028). Most of the patients with lupus enteritis showed good response to high-dose intravenous steroids and there was no death directly associated with lupus enteritis.
Bisphosphonate use does not significantly affect the clinical results during conservative treatment for OSFs. However, the occurrence of the IVC sign was related to medication history. Although further studies are needed to verify our findings, these results suggest that suspension of bisphosphonate use should be considered during the fracture healing period for acute OSFs.
Background Recent studies demonstrated that sodium chloride (NaCl) can be a risk factor for autoimmune disease through the induction of pathogenic IL-17 producing T helper (Th17) cells. Objectives This study was aimed to evaluate the potential effect of NaCl on Th17 differentiation in patients with rheumatoid arthritis (RA) and on the inflammation in collagen induced arthritis (CIA) model. Methods Peripheral blood mononuclear cells (PBMC) obtained from RA patients were cultured under high salt condition, and analyzed using flowcytometry to determine Th17 population. For evaluation of in vivo effect, CIA mice were fed with normal diet (control group) or high salt diet ad libitum (high salt group). Clinical assessment was performed daily based on visual scoring of paw swelling. The arthrogenic differentiation of mouse bone marrow derived cells and mouse splenocytes were evaluated with tartrate-resistant acid phosphatase (TRAP) staining and flowcytometry, respectively. Results NaCl promoted the induction of Th17 cells from PBMC in RA patients. Th17 differentiation was progressively upregulated as NaCl concentration increased upto 60 mM. Correspondingly, high salt diet exacerbated the arthritis of CIA mice. The arthritis score was considerably elevated in high salt group compared with control group. In high salt group, osteoclast differentiation represented by TRAP activity was more prominent. We also observed the increased expression of CD4+ RORrt+ cells in spleen of high salt fed mice. Conclusions This study suggests that NaCl can aggravate arthritis via Th17 differentiation. High salt condition can contribute to the development and progression of RA. References Kleinewietfeld, M., et al., Sodium chloride drives autoimmune disease by the induction of pathogenic T17 cells. Nature, 2013. Wu, C., et al., Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1. Nature, 2013. 496(7446): p. 513-7. Acknowledgements This work was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A092258). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5138
Background Since the concept of reprogramming mature somatic cells to generate induced pluripotent stem cells (iPSCs) was demonstrated in 2006, iPSCs have become a potential substitute for embryonic stem cells (ESCs) given their pluripotency and “stemness” characteristics, which resemble those of ESCs. Objectives We investigated to reprogram fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) to generate iPSCs using a 4-in-1 lentiviral vector system. Methods A 4-in-1 lentiviral vector containing Oct4, Sox2, Klf4, and c-Myc was transduced into RA and OA FLSs isolated from the synovia of two RA patients and two OA patients. Immunohistochemical staining and real-time PCR studies were performed to demonstrate the pluripotency of iPSCs. Chromosomal abnormalities were determined based on the karyotype. SCID-biege mice were injected with iPSCs and sacrificed to test for teratoma formation. Results After 14 days of transduction using the 4-in-1 lentiviral vector, RA FLSs and OA FLSs were transformed into spherical shapes that resembled embryonic stem cell colonies. Colonies were picked and cultivated on matrigel plates to produce iPSC lines. Real-time PCR of RA and OA iPSCs detected positive markers of pluripotency. Immunohistochemical staining tests with Nanog, Oct4, Sox2, Tra-1-80, Tra-1-60, and SSEA-4 were also positive. Teratomas that comprised three compartments of ectoderm, mesoderm, and endoderm were formed at the injection sites of iPSCs. Established iPSCs were shown to be compatible by karyotyping. Finally, we confirmed that the patient-derived iPSCs were able to differentiate into osteoblast, which was shown by an osteoimage mineralization assay. Conclusions FLSs derived from RA and OA could be cell resources for iPSC reprogramming. Disease- and patient-specific iPSCs have the potential to be applied in clinical settings as source materials for molecular diagnosis and regenerative therapy. References Takahashi K, Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006, 126:663-76. Tiscornia G, Vivas EL, Izpisúa Belmonte JC: Diseases in a dish: modeling human genetic disorders using induced pluripotent cells. Nat Med 2011, 17:1570-6. Grskovic M, Javaherian A, Strulovici B, Daley GQ: Induced pluripotent stem cells–opportunities for disease modelling and drug discovery. Nat Rev Drug Discov 2011, 10:915-29. Acknowledgements This work was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A092258). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4862
Background Systemic lupus erythematosus (SLE) is an autoimmune disease in which various organs and tissues are damaged through abnormal immune responses mediated by tissue-binding autoantibodies and immune complex deposition. As the majority of SLE patients are women of child-bearing age, estrogen has been suggested to play an important role in the pathogenesis of SLE. One of the proposed roles of estrogen is to increase autoantibody production. IL-21, a common-γ chain cytokine, has been shown to be crucial in the differentiation of activated B cells into plasma cells. Objectives Based on these concepts, we investigated the effect of estrogen on the production of IL-21 by T cells and subsequent B cell activation in SLE patients. Methods Peripheral blood mononuclear cells (PBMCs) were obtained from peripheral blood of 23 SLE patients and 16 healthy controls. CD4+ T cells, non CD4+ T cells and B cells were isolated using microbeads. Isolated cells were treated with 17-β estradiol at various concentrations for 48hrs. The expression of IL-21 and its receptor was assessed by measuring the level of protein and mRNA using ELISA and RT-PCR, respectively. The level of immunoglobulin G was measured with specific ELISA. Results The expression of IL-21 and its receptor in serum, PBMCs, and CD4+ T cells were higher in the patients with SLE compared to healthy controls. Exposure of CD4+ T cells from SLE patients to 17-β estradiol leads to a dose-and time-dependent increase in the IL-21 expression. The increase was abolished in the presence of MAP kinase (MEK, p38, JNK) inhibitors. B cells of healthy controls showed an increased antibody production when they were co-cultured with estrogen treated CD4+ T cells of patients with SLE. Treatment with anti-IL-21 antibody abrogated the increased antibody production of the co-culture systems, suggesting the increase was mediated by IL-21 dependent manner. Conclusions Estrogen upregulates IL-21 expression of CD4+ T cells via MAPK dependent pathways in SLE patients, which in turn induces increased antibody production by B cells. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.3160
Background Gout is a chronic inflammatory disease of which the development is associated with metabolic abnormality caused by obesity. However, there are a substantial number of non-obese patients (body mass index (BMI) <25 kg/m2) who develop gout in Korea. As it has been suggested that accumulation of visceral fat, rather than subcutaneous fat is associated with metabolic abnormality and hyperuricemia in patients with gout, we hypothesized that visceral fat accumulation was increased in non-obese gout patients. Objectives In the present study, we characterized the components of metabolic syndrome, and examined the association of visceral fat obesity and gout, especially focused on non-obese population. Methods One hundred and three male patients with primary gout and 204 age - matched healthy controls who attended health check-up examination were recruited by medical chart review. Visceral fat area (VFA) was measured by bioelectrical impedance analysis (BIA), and VFA>100cm2 was defined as visceral fat obesity (VFO). The frequency of VFO was compared in patients and control groups. The frequency of metabolic syndrome as well as its components was investigated. Results The prevalence of metabolic syndrome in patients with gout was 31.7% (33/104) according to modified ATP III criteria. BMI (26.3±3.8 vs. 23.4±2.4 kg/m2, P<0.001), waist circumference (91.2±9.7 vs. 82.3±7.5 cm, P<0.001), total fat mass (20.8±7.6 vs. 15.1±4.4 kg) the serum triglyceride level (178.6±99.7 vs. 89.9±38.3 mg/dL), the serum glucose level (101.2±21.3 vs. 89.8±6.8) were significantly greater in patients than controls. VFA was increased in gout patients compared to controls (115.8±27.0 vs. 97.7±20.2 cm2, P<0.001) and the prevalence of VFO was also higher in patients group (71.8% vs. 41.2%, P<0.001). There were significant correlations between VFA and the serum triglyceride level (Spearman's rho =0.274, P<0.001) and the serum glucose level (rho =0.324, P<0.001). In non-obese subgroup analysis (gout patients =38, healthy controls =150), VFA (98.7±19.3 vs. 91.0±16.7, P=0.016) and the frequency of VFO (47.4 vs. 27.3%, P=0.017) remained significantly higher in patients group. There was no difference in either BMI or the total fat mass between patients and controls in the non obese subgroup. Conclusions VFO determined by BIA is more frequently observed in patients with primary gout compared to healthy controls, even in non-obese subgroup analysis and VFA correlated well with components of metabolic syndrome. Thus, it seems that VFO may properly represent metabolic derangement in both obese and non-obese patients with gout. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3185
Background IL-33 and its receptor, ST2, are associated with many inflammatory disorders. However, the data on IL-33/ST2 in Sjögren's syndrome (SS) is very limited. Objectives To evaluate the expression of IL-33 and its receptor in sera and salivary tissues obtained from patients with primary Sjögren's syndrome (pSS) and to investigate the possible relationship with clinical profiles. Methods Serum IL-33 and soluble ST2 (sST2) of 55 patients with pSS and 48 controls were determined using ELISA, and assessed for correlation with clinical profiles. The expression of IL-33/ST2 in salivary tissues was investigated by immunohistochemical (IHC) staining, and was further characterized by confocal microscopy. We also measured ST2 expression in peripheral blood mononuclear cells (PBMCs) of pSS patients, and IL-33 production in salivary glandular epithelial cell by pro-inflammatory stimuli. Results The serum levels of IL-33 and sST2 were higher in pSS patients compared to healthy controls (P=0.018 and P<0.0001, respectively). Among pSS patients, serum sST2 concentration was associated with thrombocytopenia (P=0.029) and duration of disease (p=0.013). Contrary to sST2, ST2 was downregulated in PBMCs obtained from pSS patients. The expression of IL-33 and ST2 was elevated in salivary gland of pSS patients with grade 2 inflammation, and decreased as inflammation progresses. In pSS patients, IL-33 was mainly observed in epithelial cells and endothelial cells of gland tissue. The production of IL-33 mRNA by salivary gland epithelial cell line was increased under stimulation with interferon-γ. Conclusions IL-33 and sST2 concentrations were elevated in sera of pSS patients, whereas ST2 in salivary gland and PBMC of pSS patients showed downregulated expression. This result suggests that IL-33/ST2 axis might have a role in the pathogenesis of pSS. References Schmitz, J., et al., IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity, 2005. 23(5): p. 479-90. Palmer, G. and C. Gabay, Interleukin-33 biology with potential insights into human diseases. Nat Rev Rheumatol, 2011. 7(6): p. 321-9. Moussion, C., N. Ortega, and J.P. Girard, The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel `'alarmin”? PLoS One, 2008. 3(10): p. e3331. Acknowledgements This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI13C0016). Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4921
BackgroundCardiovascular (CV) disease is a leading cause of morbidity and mortality in patients with rheumatoid arthritis (RA).ObjectivesThe aim of this study is to assess the 10-year CV risk using three different CV risk score calculators in RA patients, and to investigate the correlation between the calculated risk and subclinical atherosclerosis.MethodsA total of 147 consecutive patients with RA underwent the carotid ultrasound to measure the carotid intra media thickness (IMT). The estimated 10-year CV risk by the systematic coronary risk evaluation (SCORE) model, the Framingham risk score (FRS), and the atherosclerotic CV disease (ASCVD) risk estimator, was modified according to the EULAR guideline. The association of modified CV risk with the carotid IMT was analysed.ResultsThe carotid ultrasound revealed 0.74 mm of mean common carotid artery (CCA) IMT and 44.9% of carotid plaques in the study population. The median of the modified 10-year CV risk evaluated by SCORE, FRS, and ASCVD was 1.5 (Interquartile range [IQR] 0-3), 6.9 (IQR 3.1-11.5), and 3.4 (IQR 1.1-7.8), respectively. When classified by the criteria of the CV risk calculators, 9 (6.1%), 11 (7.5%), and 36 (24.5%) of RA patients were included in the higher risk groups of the respective risk estimators. Patients in high risk groups had significantly greater mean CCA IMT with more frequent carotid plaques, compared to patients in lower risk groups, regardless of the CV risk calculators. The modified CV risk estimated using three different models was clearly correlated with the mean CCA IMT.ConclusionsThe estimated 10-year CV risk was well correlated with the morphological evidence of subclinical atherosclerosis. This study indicates that the assessment of the CV risk using the risk score calculators would be useful in clinical practice for management of RA.ReferencesPeters, M.J., et al., EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis. Ann Rheum Dis, 2010. 69(2): p. 325-31.Park, Y.B., et al., Atherosclerosis in rheumatoid arthritis: morphologic evidence obtained by carotid ultrasound. Arthritis Rheum, 2002. 46(7): p. 1714-9.AcknowledgementsThis study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020).Disclosure of InterestNone declared
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.