Aca 2013 Abstract Export Plenary Session: Plenary Session 1: Novel aspect of therapeutics of autoimmune diseases
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- P1-009 MYOID CELLS PLAY A KEY ROLE IN MYASTHENIA GRAVIS AND HYPERPLASIA
- P1-010 PROTEOMIC PROFILING OF AUTOIMMUNITY REPERTOIRES WITHIN MULTIPLE SCLEROSIS UTILIZING ANTIGEN ARRAYS AND HIGH-DENSITY PEPTIDE MICROARRAYS
- P1-011 GAMMADELTA T CELLS INFILTRATION AND PROINFLAMMATORY CYTOKINES PRODUCTION IN PATIENTS OF TAKAYASU ARTERITIS
- P1-012 CHILDHOOD PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM: A REPORT OF TWO CASES
- Background and Objective
- Funding
- Objective
- P1-014 MIXED CONNECTIVE TISSUE DISEASE WITH MANIFESTATION OF THROMBOANGIITIS OBLITERANS
- P1-015 SOCS3 METHYLATION IN SYNERGY WITH REG OVEREXPRESSION TO ACCELERATE INFLAMMATION-LINKED PANCREATIC CARCINOGENESIS
- P1-016 ARTHRITIS ATTACK DUE TO MEAT CONSUMPTION
- P1-017 PULMONARY INVOLVEMENT IN POLYMYOSITIS AND DERMATOMYOSITIS
- Key words
Keywords : Evans syndrome, autoimmune hemolytic anemia, immune thrombocytopenia P1-008 CHANGES OF T REGULATORY CELLS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE L. Jurgauskiene1, V. Sileikiene2, E. Danila2, R. Malickaite1 1Laboratory of Immunology, Vilnius University, Vilnius, Lithuania 2Center of Pulmonology and Allergology, Vilnius University, Vilnius, Lithuania Background and aims Chronic obstructive pulmonary disease (COPD) is characterized by progressive airway obstruction and airway inflammation. What cells and how they are causing this ongoing chronic inflammation in airways are still unknown. Researchers suggest that T regulatory cells may play a role in COPD as it is thought that COPD is an autoimmune disease. Methods We analysed T regulatory cells CD3+CD4+CD25+CD127dim and CD3+CD4+CD25bright in peripheral blood samples of patients (pts) with different COPD stages. 60 pts (mean age * 53 ± 15 yrs), where I gr. * 20 pts, healthy people, II gr. * 20 pts with mild and moderate COPD (FEV1/FVC < 0.7, FEV1 80% and 50% FEV1 80%), III gr. * 20 pts with severe and very severe COPD (FEV1/FVC < 0.7, 30% FEV1 < 50% and FEV1 < 30% or FEV1 < 50% analysed. Peripheral blood samples were analyzed by flow cytometry (BD FACSCalibur) using four color monoclonal antibodies to cell surface antigens. Results Our study showed no significant differences in number of CD3+CD4+ CD25+CD127dim T cells (1.1±0.7; 0.9±0.8; 0.8±0.6 respectively), but we noticed that there is a tendency that these cells are decreasing with severe of COPD. While the number of CD3+CD4+CD25bright T cells was significant (p < 0.05) decreased in III group comparing with other two groups (3.2±1.2; 3.4±1.3; 2.5±1.3 respectively). Conclusions According to our assay results we can say that CD3+CD4+CD25bright and CD3+CD4+ CD25+CD127dim T cells are playing a role in COPD inflammation and we can speculate that COPD could be an autoimmune disease. P1-009 MYOID CELLS PLAY A KEY ROLE IN MYASTHENIA GRAVIS AND HYPERPLASIA I. Kamo1, H. Tomoyasu2, A. Kikuchi3 1Bio Lab., System Instruments Co. Ltd., Sagamihara, Japan 2Respiratory, Omori Red Cross Hospital, Omori, Japan 3Department of Physics and Mathematics, College of Science and Engineering Aoyama Gakuin University, Sagamihara, Japan Autoimmune disease myasthenia gravis is associated as much as ~80% with thymic hyperplasia where many B-cells and IL-2 producers, but virtually no IL-4 or IFN-γ producers, are proliferating in an autonomous and/or cytokine dependent fashion. Increased numbers of precursor myoid cells were also detected here with specific antibodies against new 80-kDa and 100-kDa haemopoietic factors purified from rat myoid cells. They can distinguish hyperplasia from thymoma. The myoid cell conditioned medium, containing IL-1, IL-6 and IL-7 in addition to the above factors, induced antigen independent IL-2 production from thymocytes and stimulated the proliferation of lymphocytes and monocytes. IL-2, the only lymphokine produced here, is not the B-cell proper. IL-2 and myoid cell factors are likely to be overproduced according to the increases of their producers, thus forming a new B-cell stimulatory cytokine network. We tested this possibility by constituting mimic hyperplastic thymic conditions: nude mouse splenocytes that include functional B-cells and antigen presenting cells, but essentially lack mature Th1- and Th2-cells, were cultured in the presence of IL-2 and myoid cell factors. When combined, they indeed induced antigen specific B-cell responses in a synergistic fashion, whereas each factor alone poor responses. This cocktail also induced immunoglobulin class switches from IgM to IgG subclasses. We believe that myoid cells play an important role in forming lympho-proliferative cytokine network (hyperplasia) and present their antigens to the corresponding B-cells, thus myoid-muscle antigen specific B-cells are selectively activated here (myasthenia gravis). The mechanism of myoid cell development remained to be elucidated. P1-010 PROTEOMIC PROFILING OF AUTOIMMUNITY REPERTOIRES WITHIN MULTIPLE SCLEROSIS UTILIZING ANTIGEN ARRAYS AND HIGH-DENSITY PEPTIDE MICROARRAYS B. Ayoglu1, A. Zandian1, A. Häggmark1, B. Forsström1, M. Khademi2, T. Olsson2, M. Uhlén1, J.M. Schwenk1, P. Nilsson1 1SciLifeLab Stockholm, KTH - Royal Institute of Technology, Solna, Sweden 2Department of Clinical Neuroscience, Karolinska Institute, Solna, Sweden Broad scaled screening and profiling of autoantibody repertoires for the discovery of new autoimmune targets requires large antigen collections representing a significant part of the human protein coding genes. We have here utilized both planar and bead based protein arrays containing large sets of protein fragments from the Human Protein Atlas (www.proteinatlas.org) as well as ultra-high-density peptide microarrays for the profiling of plasma and CSF samples within multiple sclerosis. More than 11.000 protein fragments on planar microarrays, representing more than one third of the human protein coding genes, were initially screened with 90 plasma samples and followed up by a verification phase with 380 samples on 380 targets on suspension bead arrays. The outcome was 51 potential autoimmunity targets differentiating between subgroups of multiple sclerosis.1 Follow up studies is initiated where these selected candidate targets together with other suggested autoimmune targets are profiled with 4000 multiple sclerosis related samples. Ultra-high density peptide microarrays were also utilized for screening for novel autoimmunity targets. The peptide arrays were designed with either 2 million peptides with whole proteome coverage with 6 out of the 12 amino acids overlap or 150.000 peptides representing a selected set of targets and then also enabling a higher resolution with 11 amino acids in overlap. The whole proteome arrays revealed a frequently repeated and specific part of a receptor domain as a potential novel autoimmunity target in multiple sclerosis. 1 Ayoglu etal, Autoantibody profiling in multiple sclerosis using arrays of human protein fragments. Molecular & Cellular Proteomics June 2013 P1-011 GAMMADELTA T CELLS INFILTRATION AND PROINFLAMMATORY CYTOKINES PRODUCTION IN PATIENTS OF TAKAYASU ARTERITIS L. Pan1, Y.M. Liu2, T. Wang1 1Rheumatology and Immunology, An Zhen Hospital Affiliated to Capital Medical University, Beijing, China 2Cardiac Surgery, An Zhen Hospital Affiliated to Capital Medical University, Beijing, China Background and aims: Series of lymphocytes are recruited and and may produce cytokines which involved in the lesions of the aortic wall to participate in the pathogenesis of TA, but the mechanism is not clear. Mathods: Blood samples will be collected from 5 TA patients and 5 healthy controls; tissues of arota will be taken from a TA patient by surgery. Cytometric Bead Array Flex Set was used to analyze the proinflammatory cytokines production in serum and immunohistochemical staining to detect T cells infiltration in tissues of arota of TA patients. Results: Our study found that CD8+ T cells and gammadelta T cells infiltration in aorta tissue of TA patient, CD8: HLA - I and NKG2D: MICA antigens presented process were showed in aorta tissue of TA patient (Fig 1). Serum inflammatory cytokine IL-8 and IL-9 levels were significantly higher in TA patients than that of normal control group (P<0.05), IL-6 and TNF-α levels also tended to increased. Conclusion: Gammadelta T cells activated by accepted antigen through CD8: HLA - I and NKG2D: MICA pathway, and then infiltrate in the aortic wall and produce inflammatory cytokines such as IL-8, IL-9, IL-6 and TNF-α to participate in the pathgenesis of TA. 
P1-012 CHILDHOOD PRIMARY ANGIITIS OF THE CENTRAL NERVOUS SYSTEM: A REPORT OF TWO CASES C. Tan1, C.B. Bernal1, S.V. Navarra1 1Rheumatology, University of Santo Tomas Hospital, Manila, Philippines Background and Objective: Primary angiitis of the central nervous system (PACNS) is a rare disease wherein the pathogenesis is not well understood. It has an estimated annual incidence of 2.4 cases per 1 million person-years. Middle aged men are more often affected with a median age of approximately 50 years. On literature review, Lindsley et al (2005) reported that there are fewer than 50 cases in children that were published. This paper aims to present 2 pediatric cases of PACNS seen in UST Hospital. Case 1: An 11 year old, female presented with sudden onset of drowsiness with left sided weakness. Laboratory work-ups were unremarkable, ANA panel was negative, blood cultures revealed no growth, MRI revealed subacute infarct in the right MCA distribution and MRA revealed stenosis of the anterior cerebral artery and right middle cerebral artery. Case 2: An 11 year old male presented with chronic insidious headache for four years. He was initially managed as a case of migraine and vertigo, blood examinations were unremarkable, however on further work-ups, MRA revealed irregularities on the left posterior cerebral artery consistent with vasculitis. Conclusion: There are no controlled trials on the treatment of PACNS and therapy is based on principles extrapolated from systemic vasculitis. Both patients were given glucocorticoids and cyclophosphamide which apparently arrested progression, although residual neurologic deficit in one patient additionally required intensive physiotherapy. Funding: Lupus-Inspired Advocacy Project of Rheumatology Educational Trust Foundation Inc. P1-013 BIOENERGETICS OF THE SPINAL CORD TISSUE IN EXPERIMENTAL ALLERGIC ENCEPHALITIS OF RATS M. Al Shamsi1, A. Shahin1, A.K. Souid2, E.P.K. Mensah-Brown3 1Microbiology & Immunology, United Arab Emirates University, Al-Ain, United Arab Emirates 2Paediatrics, United Arab Emirates University, Al-Ain, United Arab Emirates 3Anatomy, United Arab Emirates University, Al-Ain, United Arab Emirates Introduction: Experimental autoimmune encephalomyelitis (EAE). a rodent model of relapsing/remitting multiple sclerosis (MS), is a CD4+ T cell-mediated inflammatory disease of the central nervous system (CNS). Demyelination and axonal damage, characteristics of EAE have been attributed also to dysregulation in mitochondrial function. Objective: To demonstrate that cellular respiration or bioenergetics of the CNS could predict prognosis of EAE. Aims of study:To determine whether functional state of neuronal mitochondria after disease induction was linked to severity of EAE. Methods:Susceptible Dark Agouti (DA) and resistant Albino Oxford (AO) rats were monitored for induction, height of and recovery from neurologic disease after immunization with myelin basic protein and complete FreundÕs adjuvant. Sections of the lumbar region of the spinal cord were analyzed for cellular respiration by measuring oxygen and ATP content using a phosphorescence analyzer. Caspase activity, histological signs of inflammation and cell damage were also determined by HPLC, FACS, cytochrome C oxidase immunohistochemistry, light and electron microscopy. Result: Our results revealed preserved respiration and ATP content of the CNS throughout the course of disease. This was associated with intact and normal mitochondria. Transient caspase-3 activity observed and confirmed by HPLC, FACS and caspase-3 immunohistochemistry in DA rats at the height of disease disappeared on recovery. In addition, evidence of demyelination was unremarkable. Conclusion:Our results suggest that recovery from EAE might be attributable to the preserved bioenergetics in this initial wave of the disease. P1-014 MIXED CONNECTIVE TISSUE DISEASE WITH MANIFESTATION OF THROMBOANGIITIS OBLITERANS D. Mulya1, N. Sukmana2 1Internal Medicine, Gadjah Mada University, Yogyakarta, Indonesia 2Allergy and Clinical Immunology, University of Indonesia, Jakarta, Indonesia Introduction Thromboangiitis obliterans (TAO) is a recuring progressive inflamation and thrombosis of small and medium arteries and vein of the hand and feet. Risk factor associate with thromboangiitis obliteran is a heavy smoker.Upper extremity digital ulceration due to ischemia also occur as a complication of Mised Connective Tissue Disease (MCTD) and vasculitis. We report 53 years old man with MCTD and amputated finger diagnose as thromboangiitis obliteran. Case Presentationblackish A 53 years old man complained of swelling and blackish at end of his hand since two month ago. Two weeks before admittance, tip of his finger amputated by itself. Patient also had diabetes and smoking since the age of twenty. On examination amputated finger was found at the right hand from digiti I-V. Swelling was also found in his right palm. Glucose level was 360 mg/dl. ANA test 1/1000. RNP/sm ++, CRP level was 41,2, ESR was 260, ACA IgG and IgM negative. There was a plaque and stenosis 50-75% in his brachial artery and his left and right ulnar radialis with minimal blood flow in his right hand. Patients was diagnose as MCTD and TAO. Patients was adviced to stop smoking and treated with cyclophosphamid 500 mg every two weeks, methylprednisolon 60 mg tappering off, cilostazol 50 mg bd, vitamin D, folic acid and insulin. Conclusion We report 53 years old man with TAO and MCTD. Autoimmune disease and comorbidities in patient brings challenge in therapy and futher prognosis. 
P1-015 SOCS3 METHYLATION IN SYNERGY WITH REG? OVEREXPRESSION TO ACCELERATE INFLAMMATION-LINKED PANCREATIC CARCINOGENESIS M. Xiang1, J. Wang2 1College of Pharmacy, Tongji Medical College, Wuhan, China 2Dept of Pharmacology, Medical CollegeWuhan University of Science and Technology, Wuhan, China Background and aims: We evaluated the effect of SOCS3 methylation in synergy with RegIII overexpression in the inflammatory environment to accelerate pancreatic carcinogenesis. Methods: Real-time PCR and methylation-specific PCR were carried out in tumor material from 36 pancreatic cancer (PaC) patients and 4 PaC cell lines BxPC-3, Mia Paca-2, PANC-1, SW1990 to assess RegIIImRNA expression and the methylation status of the SOCS3 CpG island respectively. SOCS3 gene was transfected into exogenous RegIII-induced PaC cell lines and silenced using siRNA in normal pancreatic epithelial cell line HPDE6C7 in vitro to assess the status of SOCS3 interferes with exogenous RegIII in cell growth. Results: Clinical observations showed that SOCS3 methylation and RegIII overexpression have independent correlation with the clinicopathological factors including inflammation history, maximal tumor size, tumor differentiation and TNM stage. And RegIII mRNA expression in the samples with SOCS3 methylation was significantly higher than those with SOCS3 unmethylation. And we identified aberrant SOCS3 methylation in PaC cell lines associated with transcriptional downregulation. Treatment of the demethylating agent 5-aza-2'-deoxycytidine restored SOCS3 expression of SW1990 cells. Overexpression of SOCS3 in PaC cells inhibited the proliferation-promoting effect of exogenous RegIII. Conversely, siRNA-mediated knockdown of SOCS3 enhanced RegIII-induced cell proliferation of HPDE6C7 cells. Conclusions: SOCS3 methylation may synergize with RegIII overexpression to correlate with accelerated onset of inflammation-linked pancreatic carcinogenesis, suggesting SOCS3 is a promising molecular target for the control of RegIII-stimulated pancreatic carcinogenesis. P1-016 ARTHRITIS ATTACK DUE TO MEAT CONSUMPTION A. Kutlu1, S. Ozturk1, O. Taskapan2, Y. Onem3, M.Z. Kiralp4, L. Ozcakar5 1Allergy and ?mmunology, GATA Haydarpa?a training Hospital, Istanbul, Turkey 2Allergy and ?mmunology, Yeditepe University, Istanbul, Turkey 3Internal medicine, GATA Haydarpa?a training Hospital, Istanbul, Turkey 4physical medicine and rehabilitation, GATA Haydarpa?a training Hospital, Istanbul, Turkey 5physical medicine and rehabilitation, Hacettepe University, Ankara, Turkey 32-year-old woman was seen for a possible diagnosis of food allergy. She had a diagnosis of rheumatoid arthritis and had been monitored for the last 8 years . On detailed questioning, she reported having several arthritis episodes when she ate a diet rich in animal food (eggs, milk, and meat). The episodes started 6-10 hours after ingestion of animal protein (most severe with meat) and lasted 2-3 days. She was free of arthritic episodes when she stopped ingesting animal products. She did not notice any symptoms when she followed a vegetarian diet composed of plant proteins (peas, lentils, beans, etc). Gouty arthritis was ruled out based on clinical signs and several normal uric acid measurements. When the patient underwent skin testing and oral diet challenge, she reported that she had ingested meat the night before the test in order to demonstrate her complaint of arthritis. During physical examination on the day of testing, swelling, erythema, and tenderness were detected on the left knee joint. Allergy skin testing was negative for all types of aforementioned food. Allergen-specific, cutaneous lymphocyte antigenpositiveT cells have been shown to play a role in delayed eczematous skin reactions in atopic dermatitis.4 We believethat a similar type of organ-specific type IV immunologic reaction might have taken place in our patientÕs joints. It has been mentioned that food-related problems of RA patients might reflect an adverse additive effect of multiple hypersensitivity reactions mediated by immune complexes promoting autoimmune reactions in the joints P1-017 PULMONARY INVOLVEMENT IN POLYMYOSITIS AND DERMATOMYOSITIS A. Zoto1, H. Hafizi2, T. Backa1, R. Osmenaj3, A. Harxhi4, Z. Ylli5 1Department of Rheumatology, University Hospital Center “Mother Theresa”, Tirana, Albania 2Department of Lung Diseases, University Hospital of Lung Diseases “Shefqet Ndroqi”, Tirana, Albania 3Department of Radiology, University Hospital Center “Mother Theresa”, Tirana, Albania 4Department of Infectious Disease, University Hospital Center “Mother Theresa”, Tirana, Albania 5Department of Immunology, University Hospital Center “Mother Theresa”, Tirana, Albania Background and aims: Polymyositis and Dermatomyositis are systemic inflammatory diseases that affect skeletal muscles and other internal organs such as lung. Pulmonary involvement in polymyositis and dermatomyositis includes interstitial lung disease, aspiration pneumonia, respiratory muscle weakness. The aims of this study was the identification of pulmonary involvement in patients with polymyositis and dermatomyositis, their assessment in relation to alterations of immunological examinations Methods: This is a cohort prospective study that analyzed 51 patients with polymyositis and dermatomyositis. The laboratory tests requested for the patients such as anti-nuclear antibody, anti-histidyl t ribonucleic acid synthetase antibody. Pulmonary high resolution computed tomography and pulmonary function test were performed for the patients. Results: Interstitial lung disease was found in 15 (29.4%) patients, aspiration pneumonia in 6 (11.8%) patients and respiratory insufficiency in 1 (2%) patients. Restrictive ventilator insufficiency was observed in 13 (25.5%) patients. Pulmonary injuries in the group of patients with abnormal immunological laboratory tests are found in 17 (63%) of patients, while in the other group of patients who do not have positive anti-nuclear antibody and anti-histidyl t ribonucleic acid synthetase antibody, pulmonary injuries are found in 5 (20.8%) of patients. Conclusions: Pulmonary manifestations are common in polymyositis and dermatomyositis. These injuries are anatomical and functional. Immunological alterations are important factors in pulmonary injuries. Key words: myositis, lung disease, antinuclear antibody. P1-018 ANTI-NMDA RECEPTOR ENCEPHALITIS: A CASE N. Akgun1, D. Erdogan Ari1, C. Karip1, E. Gözke2, C. Agalar3 1Anesthesiology and Reanimation, Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey 2Neurology, Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey 3Infection Diseases and Clinical Microbiology, Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey BACKGROUND: A case of autoimmune encephalitis related to anti-NMDA antibody is discussed. CASE REPORT: Twenty-two years old female patient suffering from abdominal pain and nausea admitted to emergency service three times within 45 days. Headach accompanied by apathy, impaired cooperation was present at third admission. Her mother death was related to an encephalitis with unknown ethiology. Mild alteration in the intensity of left parahippocampal girus was detected on cranial MRI. CSF analysis showed the presence of PMN leukocytes (80/mm3). The patient was hospitalized for the treatment of encephalitis. The result of PCR testing for Herpes virus was negative. Autoantibody scanning showed the presence of plasma antibodies against NMDA receptors. Metilprednisolone 1000 mg/day was added to drug therapy. Following the deterioration of neurological status (GCS:7), she was accepted to ICU where intravenous immunoglobulin 0.4 mg/kg/day was administered. PET-CT showed no malignacy. Conscious but uncooperative patient received five sessions of plasmapheresis using Asai Kasei plasma exchange kit followed by immunoadsorption using the same companyÕs immunoadsorption colon. Following fifth session, immunoabsorption was discontinued due to the onset of severe fever. Two days later, ooferectomy was performed at postmortem first hour in order to detect any undiagnosed overian teratoma. Histopathological evaluation revealed no pathological findings. DISCUSSION: Anti-NMDA receptor antibody-related encephalitis in young women may be associated with ovarian teratoma (1). It can also be encountered in the absence of malignancy, in both gender, whatever the age of the patient (1). In a case series of 400 patients, exitus was observed in all of the 15 patients accepted to ICU (2).REFERENCES: 1- Neurol Clin Pract. 2012 Sep;2(3):215-223, 2-QJM. 2011 Nov;104(11):921-31 Download 1.13 Mb. Share with your friends:
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