Aca 2013 Abstract Export Plenary Session: Plenary Session 1: Novel aspect of therapeutics of autoimmune diseases
P2-051 ELEVATED CFDNA IS ASSOCIATED WITH ACTIVE LUPUS NEPHRITIS AND MAY MAINLY DERIVE FROM NETOSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS
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- Poster Session: Session 2: Systemic Sclerosis and myositis P2-052 THE EFFECTIVENESS MESOTHERAPY OF FACE PATIENTS WITH SYSTEMIC SCLEROSIS.
- P2-053 PULMONARY HYPERTENSION IN SCLERODERMA
- Conclusion
- P2-055 ASSOCIATION BETWEEN OVERLAP AUTOANTIBODIES AND OVERLAP CLINICAL FEATURES IN PATIENTS WITH AUTOIMMUNE MYOSITIS IN BULGARIAN POPULATION
- P2-056 PLASMA DNASE I WITH IMPAIRED ACTIVITY FAILS TO DEGRADE NETS AND IS ASSOCIATED WITH INTERSTITIAL LUNG DISEASE IN PATIENTS WITH DERMATOMYOSITIS
- Poster Session: Session 2: Tolerance: oral, peripheral, Treg, Tregitope P2-057 MODULATION OF NEURONAL AUTOIMMUNE IMMUNE DISORDERS WITH IRT5 PROBIOTICS
- P2-058 INDUCTION OF TOLERANCE TO PDC-E2 BY AAV MEDIATED EXPRESSION OF PDC-E2 IN MICE
- P2-059 DIVERGENCE OF T LYMPHOCYTE SUBPOPULATIONS IN QUAIL-WHITE LEGHORN, DUCK-WHITE LEGHORN CHIMERAS
- P2-060 ADIPONECTIN REDUCES HEPATIC ISCHEMIA REPERFUSION INJURY BY SUPPRESSING INFAMMATORY REACTIONS IN RATS
P2-051 ELEVATED CFDNA IS ASSOCIATED WITH ACTIVE LUPUS NEPHRITIS AND MAY MAINLY DERIVE FROM NETOSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS S. Zhang1, G. Wang1, X. Lu1 1Department of rheumatology, Chian-Japan Friendship Hospital, Beijing, China Objective. Abnormal formation and insufficient clearance of neutrophil extracellular traps (NETs) has been involved in lupus nephritis (LN) and can cause the increase of residual NETs in vivo, which is one potential source of circulating cell-free DNA (cfDNA). This study explored whether cfDNA could be a biomarker for LN. Methods. Fifty four patients with SLE and 43 age- and sex-matched healthy controls were included in the study. cfDNA concentration was measured with Picogreen Kit, low-density granulocytes (LDGs) percentage in peripheral blood mononuclear cells (PBMCs) was tested by flow cytometer and DNase I activity was measured by radial enzyme-diffusion method. Results. cfDNA in SLE group was 239.76±57.15 ng/ml, significantly higher than that in healthy control group (187.96±40.55 ng/ml, P<0.0001). cfDNA in patients with LN was significantly higher than that in patients without LN (251.8±62.45 ng/ml vs. 213.6±31.34 ng/ml, P=0.028). cfDNA in patients with active LN was significantly higher than that in patients with inactive LN (260.7±69.8 ng/ml vs. 215.9±29.1 ng/ml, P=0.0349). cfDNA positively correlated with quantitative 24-hour urinary protein (r=0.350, P=0.013), LDGs (r=0.651, P=0.002) and neutrophils (r=0.584, P<0.0001), and reversely correlated with albumin (r=-0.500, P<0.0001) and endogenous creatinine clearance rate (Ccr) (r=-0.354, P=0.044). Compared to control group, SLE group exhibited a significantly increased percentage of LDGs in PBMCs and a significantly decreased DNase I activity. Conclusion. Elevated cfDNA is associated with active LN and may mainly derive from NETosis by neutrophils as well as LDGs in SLE. cfDNA could potentially aid in the prediction of LN risk in SLE patients. Poster Session: Session 2: Systemic Sclerosis and myositis P2-052 THE EFFECTIVENESS MESOTHERAPY OF FACE PATIENTS WITH SYSTEMIC SCLEROSIS. M.L. Sukhareva1, T. Dubinina1, S.H.F. Erdes1, O.V. Pushkova1 1RAMS, State Institute of Rheumatology V.A. Nasonova, Moscow, Russia OBJECTIVE: To evaluate the efficacy of mesotherapy (MT) in patients with SSc. MATERIALS AND METHODS: The study included 22 women 11 pts (MT group) and 11 pts (control group) with SSc, the average age - 42,2 ± 12,1 years, mean disease duration - 7,5 ± 3,4 years. Medicinal homeopathic preparations (making Germany) with antioxidant and antifibrotic effect used for injection MT with, the course duration was 10 days. The efficacy evaluated by Modified Rodnan skin score (MRSS), mouth opening in mm, elastography (EG). The efficacy MT evaluated at baseline (T0), after 10 days (T1), 3 (T2) and 6 mth. (T3). RESULTS:
The difference between T0 and T1 in MT group for opening the mouth was 44,3 ± 9,8 mm (p <0,05). MRSS in MT group was significantly improved in T1 in contrast of control group, and maintained at a level of T2 and T3 (p <0,05 compared to T0). According EG in healthy individuals an area corresponding to the dermis showed a uniform red-yellow color, and in patients with SSc - blue, with sporadic inclusions islands of yellow and green. According to the results EG skin of patients in the MT group T1 was as skin of healthy individuals. The effect is maintained for 3-6 months. CONCLUSION: Application antioxidant and antifibrotic by MT in SSc should reduce the density of the skin, increase the oral cavity, helps to smooth wrinkles around the mouth with saving effect for 3 to 6 months. There was no adverse reactions. P2-053 PULMONARY HYPERTENSION IN SCLERODERMA A. Kurniawan1, N. Lugito1, M. Tjiang1, I. Wijaya1, T. Yanto1, D.L. Gaol2 1Internal medicine, University of Pelita Harapan, Jakarta, Indonesia 2Internal medicine, University of Indonesia Christian, Jakarta, Indonesia Background: Transthoracic Echocardiography (TTE) has emerged as important noninvasive method of studying cardiac abnormality. There have many report describing the pulmonary hypertension seen in patient with scleroderma. The study was carried out to detect the cardiac abnormalities in patient with scleroderma. Aim : To know an incidence pulmonary hypertension in scleroderma patients in our country. Methods: This a descriptive study, we took data retrospectively from medical record, we studied a resting TTE findings in 19 patients with scleroderma and were evaluated for incidence of pulmonary hypertension. Results: Following results of TTE in 19 scleroderma patients, 17 (89.5%) patients most were females. Mean age of the patients was 37.3 ± 12.9 years old. TTE revealed abnormality in 14 patients (73.68%). Of these findings, 2 patients (10.52%) had pericardial effusion. Eight patients (42.10%) had some valvular involvement and there were two patients (10.52%) had low left ventricular ejection fraction. Four of the 19 patients (21.05%) were diagnosed having pulmonary hypertension. Some degree diastolic dysfunction was found 8 patients (42.10%). We did not find any thrombus from TTE in our patient. Conclusion: The incidence of pulmonary hypertension in our study was 21.05%. KEY WORDS: Echocardiography, Pulmonary hypertension, Scleroderma. P2-054 5-AMINOLEVULINIC ACID PREVENTS SKIN AND INTERNAL ORGANS INFLAMMATION AND FIBROSIS IN MURINE SCLERODERMATOUS GRAFTS-VERSUS-HOST DISEASE, A MODEL FOR HUMAN SCLERODERMA C. Liu1, X. Yang2, M. Fujino1, H. Ito3, K. Takahashi3, F. Abe3, M. Nakajima3, T. Tanaka3, Y. Isaka4, H. Rakugi4, H. Zou2, X. Li1 1Division of Radiation Safety & Immune Tolerance, National Research Institute for Child Health and Development, Tokyo, Japan 2Rheumatology, Huashan Hospital Fudan University, Shanghai, China 3Division of Pharma R & D, SBI Pharmaceuticals Co. Ltd., Tokyo, Japan 4Geriatric Medicine & Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan Background Scleroderma or systemic sclerosis (SSc) is a clinically heterogeneous rheumatologic autoimmune disease characterized by skin, internal organs and blood vessels, and there is no effective therapy. The purposes of current study are to develop a model of GvHD-induced scleroderma that more fully represents human condition, and to investigate the effects of 5-aminolevulinic acid (5-ALA), an intermediate of heme synthesis, enhance HO-1 activity to cleave heme to form biliverdin, CO, and iron on this model. Methods SSc-GvHD was induced by injection of lymphocytes from B10.D2 mice into BALB/c mice deficient in mature T and B cells (recombination activating gene 2-null mice). Results We successfully established an SSc-GvHD model, which is similar to the human disease particularly in the skin, progressive inflammation and fibrosis of internal organs including lung, kidney, and liver. We found that treatment with 5-ALA and iron (Fe2+) significantly reduced progressive inflammation and fibrosis in the skin and internal organs. Furthermore, by quantitative real-time PCR analysis, 5-ALA and Fe2+ suppressed the inflammatory cytokines and TGF-beta, type I collagen mRNAs expression. These results indicate that combination treatment with 5-ALA and Fe2+ exhibited a protective effect on tissue fibrosis and inflammation of SSc-GvHD model mice. Conclusion The model of GvHD-induced SSc has shown most of symptoms of human disease and is likely to contribute to better understanding of the disease mechanism. Furthermore, efficacy of the 5-ALA has important implication for clarifying the mechanism of CO and/or HO-1 activity in autoimmune diseases, and may provide a favorable opportunity for clinical therapy. P2-055 ASSOCIATION BETWEEN OVERLAP AUTOANTIBODIES AND OVERLAP CLINICAL FEATURES IN PATIENTS WITH AUTOIMMUNE MYOSITIS IN BULGARIAN POPULATION V. Reshkova1, D. Kalinova1, R. Rashkov1 1Clinic of rheumatology, University hospital 'St. Ivan Rilski", Sofia, Bulgaria Background: Autoimmune myositis (AIM) is a syndrome characterized by involvement of the cellular and humoral immune systems in skeletal muscle pathology, response to immunotherapies and the presence of autoantibodies Abs (myositis-specific and myositis-associated autoantibodies) in the serum of some patients. Myositis Abs are collectively referred to herein as overlap Abs. Although it has been suggested that myositis Abs may identified distinct disease entities, in practice these Abs often segregate with overlap manifestations 1. Objectives: The objective of this study was to determine prevalence of overlap Abs and to analyze association between overlap clinical features and overlap Abs in patients with AIM in Bulgarian population. Methods: Sera were collected from 80 patients with AIM as diagnoses were determined using Bohan and Peter classification and Troyanov clinicoserologic classification. Sera were analyzed by Immunoblot test and enzyme linked immunosorbent assay. Association between clinical manifestation and Abs were analyzed by Chi-square analysis, FisherÕs Exact test. Positive and negative predictive values, and likelihood ratio were calculated using SPSS 13.0 for Windows. Results: Overlap Abs were presented in 70% of patients with AIM. It was found that the presence of overlap Abs was strongly associated with overlap clinical feaures at AIM diagnosis (specifity 75%, positive predictive value 89.5%, positive likelihood ratio 3.37). The sensitivity of Abs for overlap features was 84%, whereas the negative predictive value was 65%. Conclusion: In the study overlap Abs often associated with overlap manifestation. Therefore it has been suggested that much of AIM is composed of ovelap myositis. P2-056 PLASMA DNASE I WITH IMPAIRED ACTIVITY FAILS TO DEGRADE NETS AND IS ASSOCIATED WITH INTERSTITIAL LUNG DISEASE IN PATIENTS WITH DERMATOMYOSITIS S. Zhang1, G. Wang1, X. Lu1 1Department of rheumatology, Chian-Japan Friendship Hospital, Beijing, China Objective: Interstitial lung disease (ILD) is a poor prognostic factor of Dermatomyositis (DM) and its pathogenesis is not well known. DNase I unable to degrade neutrophil extracellular traps (NETs) is considered to play an important role in autoimmune disease. This study focuses on the role of DNase I in the pathogenesis of ILD in DM patients. Methods: Plasma samples from 36 patients with DM (19 with ILD) and 47 age- and sex-matched healthy controls were tested for DNase I activity, DNase I inhibitors, formation and degradation of NETs, LL-37 and circulating cell-free DNA (cfDNA). Results from DM patients with ILD (DML) were compared with those from DM patients without ILD (DMNL). Results: DM plasma induced more NETs formation than control plasma (246±93.48 RFUs vs. 191.6±52.88 RFUs, P=0.002). Plasma LL-37 and cfDNA in DM group were 48.7±11.25 ng/ml and 264.9±62.95 ng/ml, respectively, significantly higher than those in control group (33.81±13.08 ng/ml, P=0.0031; 197.1±31.36 ng/ml, P<0.0001, respectively). DNase I activity in DM group was 0.3586±0.2166 U/ml, significantly lower than that in control group (0.5442±0.2464 U/ml, P=0.0003). Furthermore, DML exhibited significantly lower DNase I activity than did DMNL (0.2607±0.1709 U/ml vs. 0.4638±0.2099 U/ml, P=0.003). Specific DNase I inhibitors were found in 36.84% of DML and 5.88% of DMNL (P=0.0257). Compared with DMNL, DML cannot degrade NETs completely (83.41%±12.64% vs. 58.58%±21.4%, P<0.0001). Conclusion: Data show that DML with impaired DNase I activity failed to completely degrade NETs, which suggests that DNase I may play an important role in pathogenesis of ILD in DM patients.   
Poster Session: Session 2: Tolerance: oral, peripheral, Treg, Tregitope P2-057 MODULATION OF NEURONAL AUTOIMMUNE IMMUNE DISORDERS WITH IRT5 PROBIOTICS C.C.S. Chae1, H.S.K. Kwon2, S.W.K. Song1, C.J.S. Chun1, I.S.H. Im1 1Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, Korea 2Microbiology and Immunobiology, Harvard Medical School, Boston, USA Alteration of gut microbiota composition is associated with diverse immune disorders and restoration of dysbiosis in disease state with beneficial microorganism could confer the health benefits. Recently we have developed a screening system to selectively identify probiotic strains that could enhance the generation of CD4+Foxp3+ regulatory T cells (Tregs). Using the system, we identified a mixture of probiotics (IRT5) that up-regulates Tregs in vivo. Administration of the IRT5 induced both T-cell and B-cell hypo-responsiveness and down-regulated T helper (Th) 1, Th2, and Th17 cytokines without apoptosis induction. It also induced generation of CD4(+)Foxp3(+) Tregs from the CD4(+)CD25(-) population and increased the suppressor activity of naturally occurring CD4(+)CD25(+) Tregs. Conversion of T cells into Foxp3(+) Tregs is directly mediated by regulatory dendritic cells (rDCs) that express high levels of IL-10, TGF-beta, COX-2, and indoleamine 2,3-dioxygenase. Administration of probiotics had therapeutic or prophylactic effects in experimental disease models of inflammatory bowel disease and in non-mucosal immune disorders such as atopic dermatitis, hapten-induced contact hypersensitivity, rheumatoid arthritis, myasthenia gravis and multiple sclerosis. The immunoregulatory effect of the IRT5 probiotics is associated with enrichment of CD4(+)Foxp3(+) Tregs in the inflamed regions. Collectively, the administration of probiotics that enhance the generation of rDCs and Tregs represents an applicable treatment of inflammatory immune disorders. This study was supported from the grants funded by the Korea Food Research Institute, GIST-Caltech Collaborative Research Projects and GIST Systems Biology Infrastructure Establishment Grant funded by the Gwangju Institute of Science and Technology (GIST). P2-058 INDUCTION OF TOLERANCE TO PDC-E2 BY AAV MEDIATED EXPRESSION OF PDC-E2 IN MICE P. Leung1, T.W. Hsu2, I.H. Lin2, M.E. Gershwin1, S.A. Shu1, P. Wu2, M.H. Tao2 1Internal Medicine: Rheumatology/Allergy, University of California Davis, Davis, USA 2Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan Background and Aims: We have focused on developing unique gene therapy approach to induce tolerance in primary biliary cirrhosis using a hepatotrophic adeno associated virus vector (AAV8) engineered with a liver-specific enhancer/promoter to over express PDC-E2 in liver. Methods : We have designed two AAV-PDCE2 constructs to express the mouse PDC-E2 in either a) the mitochondrial form (AAV8-E2-flag) or b) the cell membrane form (AAV8-HA-E2mb) and examined their ability to induce immune tolerance to PDC-E2 in a PDC-E2 immunized mouse model. The mitochondrial and membrane bound PDC-E2 were tagged with flag and HA epitopes, respectively, to distinguish transgenic PDC-E2 from endogeneous PDC-E2. AAV8 expressing the firefly luciferase (AAV8-luc) was included as a negative control. C57BL/6 mice were administered I.V. with either with 1011 vector genome of AAV8-E2-flag, AAV8-HA-E2mb, or AAV8-luc and thereafter immunized with recombinant PDC-E2 every 2 weeks. Liver specific expression of transgene were determined by measuring luciferase reporter gene expression using in vivo imaging and ex vivo imaging. Sera were collected for anti-PDC-E2 determination. Results : Luciferase was highly expressed in livers administered with AAV8/luc whereas only background level of light emission was detected with AAV8-E2-flag and AAV8-HA-E2mb. More importantly, anti-PDC-E2 was reduced mice administered with AAV8-E2-flag or AAV8-HA-E2mb when compared with control PDC-E2 only treated mice throughout. The degree of inhibition was more significant in sera from AAV8-HA-E2mb than controls. Conclusion: The liver specific expression of the PDC-E2 transgene and successful inhibition of anti-PDC-E2 in both AAV8-E2-flag, AAV8-HA-E2mb is unique and a novel strategy for restoration of tolerance P2-059 DIVERGENCE OF T LYMPHOCYTE SUBPOPULATIONS IN QUAIL-WHITE LEGHORN, DUCK-WHITE LEGHORN CHIMERAS Z.D. Li1, L. Yan1, C.Y. Dai1, X.X. Yu1, L. Rui1, X.Y. Zhou1, H.B. Cao1, W.X. Zhang1, Z.Y. Wan1, Q. Shao1, Y.N. Lu1 1Biochemistry and Molecular Biology, China Agricultural University, Beijing, China Chimerism, with coexistence of cells from the same or different species, is a reliable model for inducing immune tolerance. In avian chimeras, development of chimeric organs induces immune tolerance in chick recipient. The disorder of immune system may lead chimeras to death. In this study, we detected the divergence of T lymphocyte subpopulations in inter-species avian chimeras to investigate the mechanism of immune tolerance and rejection. Quail-White Leghorn (WL) and Peking Duck (Duck)-WL chimeras were produced by injecting dissociated blastodermal cells of quail and duck into WL embryos respectively. T lymphocyte subpopulations in spleen and thymus from died chimeras on E (Embryonic) 13-E15d, died chimeras on E21d and survival chimeras of two months were analyzed by flow cytometry. The results indicated that there were no significant differences on CD4+ T lymphocytes in thymus, but CD4+ T lymphocytes in spleen were decreased in two-months Quail-WL and Duck-WL chimeras. In Quail-WL and Duck-WL chimeras died on E13-15d, CD4+ T lymphocytes in spleen were significantly increased. Although there were no significant differences of CD4+ T lymphocytes in thymus, the CD3+ lymphocytes in thymus were sharply decreased in E21d dead Quail-WL and Duck-WL chimeras. The divergence of T lymphocyte subpopulations in chimeras may be due to chicken regulatory T cells (Tregs) which can suppress proliferation of naive CD4+ T lymphocytes to keep chimeras alive. Anti-chicken CD25 monoclonal antibody was prepared and CD25 gene expression was detected in thymus and spleen. There need further evidence to proof the potential regulation of Tregs in avian chimeras. P2-060 ADIPONECTIN REDUCES HEPATIC ISCHEMIA REPERFUSION INJURY BY SUPPRESSING INFAMMATORY REACTIONS IN RATS J. Li1, S. Nie1 1the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China Background and aims: Liver transplantation has been proven to be a successful treatment to end-stage liver disease. However, immune rejection, ischemia-reperfusion (IR) injury is an important problem that contributes to graft nonfunction or early dysfunction, which significantly affects both morbidity and mortality. In the present study, we investigated the role of adiponectin, an adipokine mainly secreted from adipocytes, in attenuating ischemia-reperfusion injury. Methods: Sprague Dawley rats were subjected to 60 min of partial hepatic ischemia followed by reperfusion. Before the induction of IR, rats were treated by an intravenous administration of either adiponectin (Adiponectin group) or phosphate buffered saline (PBS) (Control group), the sham group received no treatment. Hepatic functions, mRNA of inflammatory cytokines in liver tissue, the serum levels of related cytokines, apoptosis of hepatocyte and histological examination were assessed. Results: At 6h after reperfusion, the serum levels of hepatic enzymes in the Adiponectin group were signi?cantly lower than the Control and Sham group (P<0.05). MRNA of inflammatory cytokines and the serum levels of inflammatory cytokines expression were also suppressed. Furthermore, Adiponectin also signi?cantly reduced hepatocyte apoptosis and NF-κB activity at 24h after reperfusion. The histopathology showed mild changes in the Adiponectin group. Conclusion: Adiponectin has a protective effect against in?ammatory reactions, and reduces hepatocellular injury induced by hepatic IR in rats. Download 1.13 Mb. Share with your friends:
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