Aca 2013 Abstract Export Plenary Session: Plenary Session 1: Novel aspect of therapeutics of autoimmune diseases
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- P2-040 CHEMOKINE LEVELS AND AUTOANTIBODIES PRODUCTION IN SYSTEMIC LUPUS ERYTHEMATOSUS
- P2-041 DETECTION OF SM ANTIBODIES USING SMD3 SYNTHETIC PEPTIDE
- Objective
- Conclusion Results obtained by SmD P petide are highly sensitive and specific
- P2-042 ORGAN INVOLVEMENT AND TREATMENT EFFECT OF TUBERCULOSIS ON STEROID REQUIREMENT AMONG FILIPINO PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
- Funding
- P2-044 I. EVALUATION OF THE EFFECTS OF APPLICATION OF PULSE THERAPIES IN PATIENTS WITH NEUROLOGICAL MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS
- P2-045 LUPUS GENETICS: WHAT GWAS HAS MISSED
- P2-046 INCREASED APOPTOSIS AND ABERRANT APOPTOSIS SIGNALING PATHWAYS OF CD4+CD25+FOXP3+ REGULATORY T CELLS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
- P2-047 HYPERHOMOCYSTEINEMIA ASSOCIATED WITH INCREASED BONE RESORPTION AND DECREASED BONE FORMATION MARKERS IN FEMALE PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
- P2-048 CIRCULATING MICROPARTICLE DOUBLE-STRANDED DEOXYRIBONUCLEIC ACID IN SYSTEMIC LUPUS ERYTHEMATOSUS – ENUMERATION AND CLINICAL DISEASE ACTIVITY CORRELATION
- P2-049 AUGMENTED ANTIBODY PRODUCTION IS CONSISTENT WITH INCREASED ADHESION BETWEEN ACTIVATED CD4 T AND B CELL INTERACTION IN SYSTEM LUPUS ERYTHEMATOSUS
- P2-050 A PREGNANT WOMAN WITH SEVERE LUPUS FLARE
Background: To compare the efficacy of mycophenolate mofetil (MMF) and intravenous cyclophosphamide (IVC) pulses as induction treatment for lupus nephritis (LN) in ethnically homogeneous Korean patients. Methods: This study enrolled 49 LN patients with available kidney biopsy specimens. The renal biopsy specimens were reclassified according to the ISN-RPS classification, by a renal pathologist blinded to the previous classification. The renal outcome, i.e., complete response (CR), partial response (PR), and non-response (NR), after 6 and 12 months was defined according to the ACR 2006 response criteria for proliferative and membranous renal disease in clinical trials. Results: Of the 49 patients, 28 (57.1%) were treated with IVC and 21 (42.9%) with MMF, both in combination with prednisolone. The baseline characteristics of the two groups were comparable, except that the IVC-treated patients had lower platelet counts, lower C3 levels, and higher activity scores compared to the MMF-treated patients. CR was seen in 42.9% receiving MMF and 50.0% receiving IVC after 6 months treatment (p= 0.450) and in 52.4% in the MMF group and 46.4% in the IVC group at 1 year (p= 0.745). The number of patients achieving PR and NR did not differ significantly at 6 and 12 months between the treatment groups. Conclusion: These findings suggest that the efficacy of oral MMF at 1 year does not differ from that of IVC in induction treatment of LN in ethnically homogeneous Korean patients. MMF may be considered first-line induction therapy for treating LN in these patients. P2-040 CHEMOKINE LEVELS AND AUTOANTIBODIES PRODUCTION IN SYSTEMIC LUPUS ERYTHEMATOSUS B. Leishangthem1, A. Wanchu2, A. Sharma3, A. Bhatnagar1 1Biochemistry, Panjab University Chandigarh, Chandigarh, India 2Division of Arthritis and Rheumatic Diseases-OP09, Oregon Health and Science University, Portland, USA 3Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India Background and Aim: Systemic lupus Erythematosus (SLE) is chronic inflammatory and complex autoimmune disease. It affects various parts of our body because of autoantigens. RANTES, chemokine and its receptor CCR5 have been associated in the pathogenesis of SLE. So a study was designed to evaluate association of anti-ds DNA, anti- Ro, RANTES and CCR5 with disease activity. Methods: For this study, blood was collected (after informed consent) from 80 SLE patients diagnosed and undergoing treatment in PGIMER along with 80 healthy controls. Levels of anti *ds DNA, anti-Ro levels and RANTES were measured using ELISA kits. Whereas the expression of CCR5 was evaluated by using FITC tagged monoclonal antibody in flow cytometer. Disease activity score was calculated by Systemic Lupus Erythematosus disease Activity (SLEDAI). Results: The levels of RANTES and CCR5 expression were found to be higher in patients 1840.48±739.42pg/ml vs 835.44±70.48pg/ml; P<0.0001 and 26.49±.16% vs 24.72±3.02%; P<0.05 respectively as compared to controls. Autoantibodies levels were also found to be higher in patients. SLEDAI score was found to be negatively correlated with elevated anti-dsDNA (p<0.05). But a moderately significant negative correlation as compared to controls was found in borderline patients for anti-Ro autoantibody (p<0.01). The levels of RANTES and CCR5 were also higher in case of patients than controls. But there was no significant correlation of RANTES and CCR5 with disease activity. Conclusion: The study shows an association of auto-antibodies, RANTES and chemokines levels with SLE. Later studies should emphasize on the anti-SSA during the diagnosis of disease.
EliA SmDP performs better than the compared Elisa with conventionally purified Sm preparation resulting in a cleary higher positive likelihood ratio supporting the high clinical value. The comparatively low sensitivity of 23% is due to the prevalence of the marker in SLE in the patients with Caucasian background. Conclusion
P2-042 ORGAN INVOLVEMENT AND TREATMENT EFFECT OF TUBERCULOSIS ON STEROID REQUIREMENT AMONG FILIPINO PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS J. Patricio1, M.T. Salvador1, S.V. Navarra1 1Department of Medicine Section of Rheumatology, University of Santo Tomas Hospital, Manila, Philippines INTRODUCTION. Tuberculosis (TB) is a leading cause of morbidity and mortality in SLE particularly in endemic countries. We describe the organ involvement and outcomes of TB infection among Filipino SLE patients, and analyzed the effect of adequate TB treatment on corticosteroid requirement. METHODS.Retrospective review of medical records of SLE patients seen at the Rheumatology Clinics of USTH who completed a minimum 6-month TB therapy was done. Average prednisone (mg/day), disease activity scores and selected laboratory parameters were recorded before, during, and upon completion of therapy. RESULTS. There were 153 episodes of TB infection in 122 SLE patients (112 females, 92%). Average age was 29.30+12.97 (range 7-67) at SLE diagnosis, with duration of 88.5+64.2 months (range 1-276) to TB diagnosis. Pulmonary TB (PTB) involvement was seen in 62%. 43% had extra-pulmonary TB (EPTB), 11.76% having solely EPTB while 13.73% were disseminated TB. EPTB included meningitis (26%), soft tissue (22%), arthritis (20.75%), genitourinary, gastrointestinal, spine and pericarditis. Average daily prednisone (mg/day) decreased from 16.45+12.58 before to 10.85+7.93 during (p<0.05), and 7.13+5.36 after TB therapy (P<0.05). Overall SLEDAI scores decreased after TB therapy. Hemoglobin (g/L) increased from 104.34+17.20 to 113.62+11.98 (p<0.05) and sedimentation rate decreased from 76.34+32.69to 26.96+15.43 post-TB therapy. CONCLUSION. Appropriate TB therapy positively impacts SLE by decreasing steroid requirement, potentially decreasing overall disease activity. Expected improvement in anemia and ESR levels suggest possible confounding effect of TB infection in assessment of their disease activity. Funding: Lupus-Inspired Advocacy( LUISA) of Rheumatology Educational Trust Fund Inc (RETFI) P2-043 GASTROINTESTINAL INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS: A CASE SERIES J.P. Patricio1, J.D. Ngo1, S.V. Navarra1 1Department of Medicine Section of Rheumatology, University of Santo Tomas Hospital, Manila, Philippines Introduction: Systemic lupus erythematosus (SLE) presents with protean clinical manifestations, with infrequent involvement of the gastrointestinal (GI) tract. This reports 3 Filipino patients whose lupus flare consisted primarily of GI involvement. Case1: 34 year old diagnosed SLE of 14 years, stable on prednisone 5mg/day and hydroxychloroquine presented with vomiting, diarrhea, abdominal pain, proteinuria and hypocomplementemia. Radiograph showed focal segmental ileus and dilated small bowel loops. Abdominal ultrasound revealed diffuse hepatic parenchymal changes, ascites and incidental pleural effusion. Her symptoms dramatically improved on high dose steroids. Case2: 44 year old SLE of 19 years duration maintained on prednisone 15mg/day and hydroxychloroquine for thrombocytopenia developed recurrent epigastric pain and vomiting. Esophagogastroduodenoscopy showed acute gastric mucosal erosions. Her symptoms were unresponsive to GI medications. High dose steroids provide almost immediate relief and there were no recurrences while tapering steroids. Cyclophosphamide therapy was eventually started for persistent thrombocytopenia. Case3: 24 year old recently diagnosed SLE with mucocutaneous lesions, positive ANA and hypocomplementemia presented with worsening epigastric pain and vomiting unresponsive to GI medications. Radiograph and CT scan showed ileus with pneumo-peritoneum suggestive of ruptured viscus. Exploratory laparotomy revealed gangrenous terminal ileum; resection with colostomy was performed. High dose steroids were simultaneously started. She was discharged improved on tapering steroids. Conclusion. We report 3 patients with GI involvement associated with active SLE, all of whom improved with high dose steroids. Early recognition of this infrequent involvement in SLE improves the prognosis and lessens overall morbidity. Funding: Lupus-Inspired Advocacy (LUISA) of Rheumatology Educational Trust Fund Inc. P2-044 I. EVALUATION OF THE EFFECTS OF APPLICATION OF PULSE THERAPIES IN PATIENTS WITH NEUROLOGICAL MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS V. Reshkova1, R. Rashkov1, S. Monov1, D. Kalinova1, T. Yoneva1 1Clinic of rheumatology, University hospital 'St. Ivan Rilski", Sofia, Bulgaria The Systemic Lupus Erythematosus (SLE) is manifesting itself with different clinic symptoms and immune phenomena. The affectation of the Central Nervous System (CNS) manifests severe effects and it is difficult to treat revealing unfavorable prognosis factors as well. The purpose of the present clinical study was to evaluate the effects of the long term application of Methylprednisolone and Cyclophosphamide Pulse Therapy in patients with manifested Central Nervous System Lupus in their clinical picture. In the Clinic of Rheumatology in Sofia took place a clinical treatment of 35 female for 12-18 months with intravenous Methylprednisolone and Cyclophosphamide Pulse Therapy. The clinical status of the patients was evaluated applying the SLEDAI, an immunological analysis and MRI of CEREBELUM. During the studied period was observed the reduction and even the disappearance of symptoms. 1. At the beginning 18 patients (52,43%) were with epileptic convulsions, meantime with 12 patients (66,7%) was observed a reduction and even disappearance of the epileptic convulsions. 2. The organic syndrome was diagnosticated with 18 patients (51,43%) while 9 of the patients (50%) ameliorated their clinical status. 3. The Lupus Headache was the most difficult one to treat. The efficiency of Pulse Therapy is evident influencing successfully the severe symptoms in the CNS Syndromes of SLE, improving and restoring the pertinent functions and increasing the patientsÕ quality of life. The of is evident influencing successfully the severe symptoms in the CNS Syndromes of SLE, improving and restoring the pertinent functions and increasing the patientsÕ quality of life. P2-045 LUPUS GENETICS: WHAT GWAS HAS MISSED? W. Yang1, Y.L. Lau1 1Peadiatrics and Adolescent Medicine, The University Of Hong Kong, hong kong, Hong Kong China Systemic lupus erythematosus is a prototype autoimmune disease with a strong genetic component. Asians have higher disease prevalence and lupus nephritis than European populations. This is consistent with our findings from meta-analysis of GWAS on two Chinese populations. Overall, around half of the susceptibility loci identified from Asian studies so far are likely to be different between Asians and European populations. This raises the question that for future risk prediction and personalized management, the analysis has to be based on studies from the relevant populations. ITGAM is a good example for subphenotype stratification and population differences, with its different allele frequencies between Asians and European populations and association with lupus nephritis. The HLA region showed most prominent association with many autoimmune diseases. Population differences and independent contributors are also prominent for this region. Thus detailed understanding of this region is important in further explaining the missing heritability, subphenotype stratification, and personalized management of the disease. Typing the HLA alleles is somewhat difficult; thus we developed a method for HLA typing using next generation sequencing with flexibility, reasonable throughput and very low cost. This method is not only suitable for HLA typing for lupus studies, it can also be used for genetic screening of other genetic disorders and for population screening. P2-046 INCREASED APOPTOSIS AND ABERRANT APOPTOSIS SIGNALING PATHWAYS OF CD4+CD25+FOXP3+ REGULATORY T CELLS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS L. Na1 1Dermatology, Southwest Hospital Third Military Medical University, Chongqing, China Background and aims:Decreased cell numbers and suppressive defects of naturally occurring CD4+CD25+FOXP3+ regulatory T cells (Tregs) play an important role in the breakdown of SLE immunetolenrance. We have peviously observed significantly increased apoptosis of peripheral blood CD4+ T cells in SLE patients. Our objective here was to detect the apoptosis of Tregs in SLE patients to see if it could contribute to reduced suppressive activity of Tregs, and further elucidate the genes and signaling pathways which trigger the apoptosis in these cells. Methods: The apoptosis of Tregs was evaluated in SLE patients and normal controls(NCs) by FACS. The suppressive activity of Tregs was measured by coculture with CD4+CD25-CD127dim/- T cells. The relationship of abnormal Tregs apoptosis with clinical parameters was analyzed by Pearson correlation analysis. Gene expression profiles of unstimulated Tregs from active SLE patients and NCs were generated by microarray analysis. Differential genes expression were verified by real time-PCR. Results: We found that the Tregs from SLE patients showed a significant elevation in apoptosis and reduction in suppressive capacity compared to NCs. The increased apoptosis of Tregs was negatively correlated with the total number of Tregs and positively correlated with disease activities. Gene expression profiles of unstimulated Tregs from recent-onset SLE subjects reveal a cellular response that could make the cells sensitive to apoptosis, partially due to the stress responses and cytokine stimulation. Conclusions: This global picture of pathway-specific expression signatures is a step further into dissecting Tregs defects in the pathogenesis of SLE. P2-047 HYPERHOMOCYSTEINEMIA ASSOCIATED WITH INCREASED BONE RESORPTION AND DECREASED BONE FORMATION MARKERS IN FEMALE PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS K. Handono1, T. Luthfia Sari2, A. Amelia Adam2, M. Zulbaidah Artamin1 1Clinical Pathology Faculty of Medicine, Brawijaya University, Malang, Indonesia 2Laboratory of Biomedical Science Faculty of Medicine, Brawijaya University, Malang, Indonesia Background. Premature osteoporosis is one of the long term complications of Systemic Lupus Erythematosus (SLE). Recent studies showed that increased level of homocysteine was detected in SLE patients and it was associated with deterioration of bone health. The aim of this study was to determine the association between homocysteine level and biochemical parameters of bone turn over in SLE patients. Subyects and Methods. Thirty-nine female patients who fulfilled ARA criteria for the classification of SLE under the age of 50 years were studied. All patients were moderately active ( SLEDAI >5). Bone turn over were assessed using βCTx ( bone degradation) and osteocalcin ( bone formation ). Laboratory parameters including serum homocysteine??, folic acid, vitamin B6, vitamin B12, βCTx, and osteocalcin were measured by ELISA method. Blood samples were taken after 10 hours fasting. Result.This study found that 71.8% of SLE patients had hyperhomocysteinemia. High homocysteine level was associated with increased levels of βCTx (p = 0.000, R = 0.943) and decreased levels of osteocalcin (p = 0.000, R = 0.771). Serum levels of folic acid, vitamin B6, and vitamin B12 tend to be low in SLE patients. A high incidence of hyperhomocysteinemia was found in premenopausal patients with SLE which affect bone metabolism. Bone diminution in SLE seems to be attributable both increased bone resorption and decreased bone formation. Keywords : SLE, homocysteine, folic acid, B6, B12, βCTx, osteocalcin, osteoporosis P2-048 CIRCULATING MICROPARTICLE DOUBLE-STRANDED DEOXYRIBONUCLEIC ACID IN SYSTEMIC LUPUS ERYTHEMATOSUS – ENUMERATION AND CLINICAL DISEASE ACTIVITY CORRELATION S.H. Tay1, A. Lateef1, D.R. Koh2, Y.C. Lim3, I. Ng1, L.H.K. Lim2 1Medicine, National University Health System, Singapore, Singapore 2Physiology, National University of Singapore, Singapore, Singapore 3Pathology, National University of Singapore, Singapore, Singapore Background: Microparticles (MP) have been postulated to be autoadjuvants in the pathogenesis of systemic lupus erythmatosus (SLE). Herein, we aim to establish the presence of extracellular DNA in the form of circulating MP DNA and attempt to correlate MP DNA levels with disease activity. Methods: MPs from plasma from SLE patients and healthy controls were pelleted using high-speed centrifuge and analyzed using flow cytometry. PicoGreen doubled stranded DNA (dsDNA) quantitation reagent was used for staining. The sensitivity of MPs to detergent Triton X-100 was assessed. Sensitivity to detergent lysis allowed for differentiation from MP dsDNA from unassociated (MP-free) dsDNA. Enumerated MP dsDNA were purified from the unassociated dsDNA using a membrane ultrafiltration spin column. Results: MP DNA of 14 SLE patients and 8 healthy controls were quantified. The median MP DNA/uL of plasma for SLE patients was significantly higher than healthy controls 2460.28 (Q1; Q3 1010.91; 3416.26) vs. 403.73 (Q1; Q3 222.26; 1801.88) (p=0.020). There was significant correlation of MP DNA concentration with anti-dsDNA immunoglobulin G (IgG) serum titres in SLE patients (r=0.818, p=0.002). MP DNA concentration correlated negatively with complement 3 levels (r=-0.501, p=0.034). The purity of MP DNA was increased from 9.22% to 83.20% following concentration with the ultrafiltration column. Conclusion: We have demonstrated the presence of MP DNA in plasma of SLE patients and healthy controls. However, the level of MP DNA in SLE patients was significantly higher than healthy controls. The level of MP DNA also correlated strongly with titers of anti-dsDNA IgG in SLE patients.
Background and aims: Molecular dissection of how T cell activation promoting B cell functionality will provide important clues to the pathogenesis of autoantibody-involved SLE pathogenesis. Methods: Using CD4 T cells either from SLE patients or activated in vitro by anti-CD3/CD28 antibodies, we have detected the adhesion between CD4 T and B cells by using a micropipette adhesion frequency assay. Activated CD4+T were further co-cultured with na•ve B cells in vitro. IgG and IgM levels in the supernatant were detected by ELISA. Results: The adhesion between activated CD4 T cells from SLE patients and B cell was much stronger than that of normal CD4T cells. With the addition of anti-ICAM-1 or anti-ICOS blockade antibodies separately, the adhesion frequency decreased. Consistent to the adhesion, IgG and IgM levels in the supernatant increased dramatically from day 4 whereas there was very little IgG and IgM detectable with the co-culture of non-activated normal T cells and B cells. The addition of anti-ICAM-1 antibodies largely blocked the production of IgG and IgM. Augmented IgG production by B cells was also observed after co-culture with CD4 T cells from SLE patients. Conclusions: Our results aforementioned demonstrated that CD4 T cells from SLE enhanced B cell-mediated antibody production, probably initiated through increased adhesion between T and B cells. ICAM-1 played important roles on both processes. This might lay the molecular foundation to study the roles of T/B cell interaction on the pathogenesis of antibody-driven SLE as well as facilitate the screening of optimized therapeutic targets in SLE.
Pregnancy in an SLE patient is associated with increased risk of adverse maternal and fetal outcomes. Lupus disease activity may flare during pregnancy or in the immediate postpartum period. Flares occur in up to 61-67% of patients if the disease was active at conception. CASE A 24 year-old woman, 7thmonth of pregnancy, came to ER due to generalized edema since 3 months ago and got worse in the last 2 days. She complained body weakness, loss of appetite, nausea, hair loss, and joint pain since 1 week before. She got SLE for 4 years but without treatment for the last 1 year. Examinations showed anemia, malar rash, and both legs edema. Hemoglobin level 7.1g/dL, ESR 89mm/hour, albumin 2.25g/dL, CRP 1.75mg/L, proteinuria +3, ANA test +, anti-dsDNA +, and low C3 C4. The assessment was SLE flare, 31/32 weeks of gestation, single live fetus, unlaboured. She was given methylprednisolone 500mg for 3 days then tapered down, azathioprine 2x50mg/day, chloroquine 1x200mg/day, blood transfusion and albumin infusion. On the 9th day, she complained of severe dyspnea and cough due to pulmonary edema. Emergency caesarian section suggested due to acute lung edema. After delivery (1550g, Apgar score 5-6), she got worse and was on mechanical ventilator. On 12th day, antibiotic was added due to pneumonia suspicion. On 17th day, she had no dyspnea, ESR 75mm/hour, proteinuria +3. We gave cyclophosphamide 500mg i.v, continued antibiotic and steroid, azathioprine was stopped. On 20th day, she was discharged with a good condition. Download 1.13 Mb. Share with your friends:
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