Aca 2013 Abstract Export Plenary Session: Plenary Session 1: Novel aspect of therapeutics of autoimmune diseases
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- Free Communication: Free Communications 1- Pearls in SLE, APS and RA research
- 065 ADIPONECTIN PROMOTES THE DIFFERENTIATION OF NAÏVE T CELL TO TH17 CELL AND AGGRAVATES COLLAGEN-INDUCED ARTHRITIS
- 066 CELLULAR- MOLECULAR RELATION OF SERUM IL10 LEVELS WITH HYPERALGESIA VARIATION ON ARTHRITIS IN RAT
- 067 ARE AUTOANTIBODIES AGAINST BETA2-GLYCOPROTEIN I REALLY ATHEROGENIC: ANSWERS FROM IN VIVO PET IMAGING STUDIES IN APOLIPOPROTEIN E-DEFICIENT MICE
- Methods and Results
- 070 ENDOGENOUS SLPI RELEASED BY RHEUMATOID SYNOVIAL FIBROBLASTS CONTROL BAFF-DEPENDENT-B CELL ACTIVATION IN VITRO AND IN THE CIA AND RA/SCID-ARTHRITIS MODELS
- 071 RENAL INVOLVEMENT MORE FREQUENT AND MAY BE LINKED TO POORER SURVIVAL AMONG FILIPINO MALES WITH SLE
- Objective
- 072 NATURAL KILLER AND NATURAL KILL T CELL DYSFUNCTION IN ADULT-ONSET STILLS DISEASE
- 073 LOW SERUM LEVEL OF 25-HYDROXYVITAMIN D3 IN NEWLY ONSET SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: INTRINSIC ABNORMALITY
- 074 MATERNAL AND FETAL OUTCOMES OF LUPUS PREGNANCIES AMONG FILIPINO PATIENTS IN A TERTIARY HOSPITAL
- Background and Objective
- 075 RECOMBINANT DOMAIN V OF BETA2-GLYCOPROTEIN I INHIBITS THE FORMATION OF ATHEROGENIC OXLDL/BETA2-GLYCOPROTEIN I COMPLEXES
Results: Without any stimulation, IP-10 was expressed the highest in the eight cytokines, the second was IL-8, the third was TNF-α. The level of IL-17 was too low to be detected. Only 8 of SLE and 1 of healthy individuals was measured minim level. The level of IP-10, IL-8 and TNF-α were higher in the SLE patients than that in the healthy control individuals(P <0.01)(Table 1). The level of IP-10 was positively related with SLEDAI score and the level of TNF-α was negatively related with C3 level. Conclusions: The serum level of IP-10, IL-8 and TNF-α were higher in the SLE patients than that in the healthy control individuals. The three cytokine may play important roles in the pathogenesis of SLE. Multiplex immunoassay is a reliable, fast, and reproducible technique to measure multiple cytokines with small volumes. Free Communication: Free Communications 1- Pearls in SLE, APS and RA research 064 AUTOIMMUNITY ACCELERATES ATHEROGENESIS: OXIDIZED-LDL/B2-GLYCOPROTEIN I COMPLEXES AND ANTI-B2-GLYCOPROTEIN I ANTIBODIES ENHANCE THE RISK OF CARDIOVASCULAR EVENTS IN ACUTE CORONARY SYNDROME L.R. Lopez1, T.P. Greco2, B. Hurley3, M. Boisen3, E. Matsuura4 1Clinical Affairs, Corgenix Inc., Broomfield, USA 2Medicine, Saint Mary's Hospital and Yale University, Waterbury, USA 3Research and Development, Corgenix Inc., Broomfield, USA 4OMIC and Cell Chemistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan Background and Aims: OxLDL/β2GPI complexes have been implicated as relevant pro-atherogenic autoantigens and associated with poor cardiovascular adverse events (AE) by triggering autoimmune pro-coagulant and pro-atherogenic mechanisms. Because anti-β2GPI antibodies accelerate the in vitro macrophage uptake and intra-cellular accumulation of oxLDL, the concurrent significance of oxLDL/β2GPI and antiphospholipid antibodies (aPL) on AE was evaluated in 339 acute coronary (ACS) patients. Methods: Consecutive ACS patients (both genders between 35-75 years) admitted to an acute care center with chest pain and suspected coronary syndromes were studied. The severity of coronary disease was assessed by angiography. The mean follow-up for AE was 2 years. Serum oxLDL/β2GPI complexes and aPL were measured by ELISA. Results: AE increased significantly in aPL+ patients with severe disease than aPL* patients (30.6% vs. 9.0%, p<0.005). Relative risk (RR) for AE of all aPL+ versus aPL* was 3.66 (95% CI 1.88-7.14, p<0.001). APL+ with oxLDL/β2GPI in 2 upper quartiles had more AE than aPL* in same quartiles (26.1% vs. 6.0%, p<0.05; RR 3.2, 95% CI 0.95-10.86, p<0.05). RR in aPL+ in 2 upper quartiles was 6.72 (95% CI 2.4-19.0, p=0.01) than aPL* in 2 lower quartiles. RR of aPL+ in the upper quartile was 13.68 (95% CI 1.8-102.4, p<0.001) than aPL* in lowest quartile. Conclusions: These results support the concept that the co-presence of oxLDL/β2GPI complexes and autoimmune aPL antibodies (anti-β2GPI and anti-oxLDL/β2GPI) significantly enhances the risk of cardiovascular AE, likely mediated by enhancing the intracellular lipid accumulation by macrophage and atherosclerotic plaque development via scavenger and Fcγ receptors. 065 ADIPONECTIN PROMOTES THE DIFFERENTIATION OF NAÏVE T CELL TO TH17 CELL AND AGGRAVATES COLLAGEN-INDUCED ARTHRITIS M. Zhang1, X. Sun1, X. Feng1, K. Gan1, W. Tan1 1Rheumatology Department The First Affiliated Hospital of Nanjing Medical University, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China Background and aims: To investigate a role of Adiponectin (AD) on the differentiation of na•ve T cell to Th17 cell and bone erosion in collagen-induced arthritis (CIA) mice. Methods: Purified na•ve T cells were cultured with TGF-β, IL-6, IL-23 in the presence and absence of AD (0.1, 1 or 10 μg/ml). After 72 hours of culture, the frequencies of Th17 cells were measured by flow cytometry; the expression of ROR-γt and IL-17 were determined by real-time PCR and ELISA. Intraarticularly injected of AD 10 μl (1 μg/1 μl) into the knee joint of CIA mice was to analysis the role of AD on CIA development and Th17 expression in vivo. Results: The frequencies of Th17 cells were significantly increased with the concentration of AD 10 μg/ml, but AD treatment with 0.1 and 1 μg/ml showed no obvious effect on the differentiation of na•ve T cell to Th17 cell. The expression of IL-17 and ROR-γt mRNA were significantly increased cupon AD 0.1 μg/ml and 10 μg/ml AD stimulation. Consistently with mRNA expression, IL-17 levels were significantly elevated in culture supernatants after 10 μg/ml AD treatment. Intraarticular injection of AD into the left knee joint of CIA mice aggravated arthritic development and bone erosion,triggered higher expression of IL-17 mRNA and its transcriptiona factor including ROR-γt, IL-21, IL-22 and IL-23 in CIA model. Conclusions: These findings identify a role of AD on enhancing the differenation of na•ve T cell to Th17 cell, contributed to CIA bone erosion in CIA mice. 066 CELLULAR- MOLECULAR RELATION OF SERUM IL10 LEVELS WITH HYPERALGESIA VARIATION ON ARTHRITIS IN RAT J. Zaringhalam Moghadam1, Z. Zeinab Akhtari2, A. Akram Eidi2 1Physiology, Shahid Beheshti University medical Science, Tehran, Iran 2Biology, Department of Biology Science and Research Branch Islamic Azad University, Tehran, Iran Introduction: Regarding to the important anti-inflammatory role of IL10during inflammation process and hyperalgesia and edema variation during CFA-induced arthritis and also the increase of Spinal mu opioid receptor (mOR) expression, we aimed to investigate the role of serum IL10 level on mOR expression and edema and hyperalgesia variation during different stages of Complete Freund`s Adjuvant (CFA) - induced arthritis in male Wistar rats. Material & Method: Mono-arthritis was induced by CFA and inflammatory symptoms (hyperalgesia and edema) were assessed on 0, 3,7th, 14th and 21st days of study. Anti-IL10was administered during the 21 days of study in different experimental groups. mOR expression were detected by western blotting. Results: Our results showed that anti-IL10 administration in AA (Adjuvant Arthritis) group caused an increase in the paw volume and hyperalgesia until 21st of study. Our study stated that there were no significant differences in spinal mOR expression between AA and AA+anti-IL10rats Conclusion: Our study confirmed that anti-IL10administration caused to hyperalgesia and edema during AA inflammation. Also these findings suggested that mOR expression increased in chronic phase of AA inflammation, however an increase in the level of spinal mu opioid receptor (mOR) expression during AA inflammation is not mediated directly via the effect of serum IL-10. 067 ARE AUTOANTIBODIES AGAINST BETA2-GLYCOPROTEIN I REALLY ATHEROGENIC?: ANSWERS FROM IN VIVO PET IMAGING STUDIES IN APOLIPOPROTEIN E-DEFICIENT MICE Y. Matsunami1, T. Sasaki2, F. Takenaka2, K. Kobayashi2, K. Kojima3, S. Kita3 1Department of Cell Chemistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan 2Collaborative Research Center for (OMIC), Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan 3IVD Development Department, Medical and Biological Laboratories Co Ltd, Ina, Japan Background: β2-glycoprotein I (β2GPI) is a major autoantigen for antiphosholipid antibodies that appear in patients with antiphospholipid syndrome (APS). Our in vitro studies have demonstrated that β2GPI specifically binds oxidized low-density lipoprotein (oxLDL) to subsequently form pro-atherogenic/proatherothrombotic IgG immune complexes. However, this proposed mechanism has not been confirmed up to this date in any type of in vivo studies. Methods and Results: We reconstructed a newly established IgG murine antibody (3H3) specific for theβ2GPI molecule when bound to oxLDL into its single chain Fv (3H3-scFv, 25 kDa) antibody variant lacking the Fc region. Both 3H3-scFv and 3H3-IgG (as full sized IgG) revealed a quite similar specificity to anti-β2GPI autoantibodies derived from APS patients and from the animal APS model NZW x BXSB Fl male mice by ELISA and immunohistochemical analysis. The specific accumulation of 64Cu-labeled 3H3-scFv was observed in Sudan IV-positive atherosclerotic lesions of aortic valves and thoracic/abdominal arteries from high fat-loaded apolipoprotein E-deficient (ApoE-/-) mice injected intravenously 24 hours prior to PET imaging. The bio-distribution analyses also confirmed the quantitative and significant accumulation. Conclusion: The demonstration of 3H3-scFv accumulated in atherosclerotic lesion after its intravenous injection represents a novel and significant observation to support the idea that APS derived autoantibodies can immunologically target atherogenic oxLDL/β2GPI complexes in arterial lesions. This interaction results in IgG immune complex formation that as previously demonstrated induce autoimmune-mediated atherosclerosis/and athero-thrombosis. Free Communication: Free Communications 1- Pearls in SLE, APS and RA research 069 CLINICAL EVALUATION OF TOTAL AND HIGH AVIDITY ANTI-DSDNA ANTIBODY EIA FOR THE DIAGNOSIS OF SYSTEMIC LUPUS ERYTHEMATOSIS H. Cao1, S. Zhou2, P. Wan1, W. Li1, T. Prestigiacomo2, J. Zheng1 1Ruijin Hospital, Jiaotong University, Shanghai, China 2CDG, Bio-Rad Laboratories, Hercules, USA This study is to investigate clinical utility of total (high and low avidity) and high avidity (HA) anti-dsDNA antibodies in an enzyme-linked immunosorbent assay (EIA). A total of 431 sera, 221 from SLE patients, 51 from patients with other autoimmune diseases and 159 from healthy subjects, were measured using five different formats of anti-dsDNA EIA kits. Two kits are commercially available at Bio-Rad Laboratories, the remaining are research use only kits. Two kits detect total anti-dsDNA IgG antibodies, two kits measure HA anti-dsDNA IgG antibodies, and one detects anti-dsDNA antibodies of both IgG and IgM isotypes. High avidity EIA tests have fewer false positives, especially in other autoimmune disease control group compared to total anti-dsDNA assays (8/51 vs 1/51 and 6/51 vs 2/51). Although all the assays were able to show a correlation of anti-dsDNA antibody with disease activity and low C3 and C4 levels (P<0.0001), inactive SLE patients have more negatives on high avidity anti-dsDNA assays. The presence of anti-dsDNA antibody in SLE patients is associated with lupus nephritis and serositis. Mann Whitney and Fisher exact analyses show there are significant differences of anti-dsDNA antibody presence and level in the patients with or without kidney damage (P<0.0001), but not in the patients with or without hematological damage (P>0.05). The ratio of HA to total anti-dsDNA antibodies is significantly higher in patients with M-SLEDAI >4 or with active kidney damage (t test, P<0.0001), and it may be useful for monitoring SLE patients as it demonstrated a correlation to disease activity. 070 ENDOGENOUS SLPI RELEASED BY RHEUMATOID SYNOVIAL FIBROBLASTS CONTROL BAFF-DEPENDENT-B CELL ACTIVATION IN VITRO AND IN THE CIA AND RA/SCID-ARTHRITIS MODELS N.W. Kam1, F. Brentano2, D. Kyburz2, S. Gay2, A. Filer3, C. Buckley3, C. Pitzalis1, M. Bombardieri1 1Experimental Medicine and Rheumatology, William Harvey Research Institute, London, United Kingdom 2Department of Rheumatology, University Hospital Zürich, Zürich, Switzerland 3Division of Immunity and Infection, College of Medical and Dental Sciences University of Birmingham, Birmingham, United Kingdom Background and aims: Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor with potent anti-microbicidal/immunoregulatory activities. Rheumatoid arthritis (RA) is characterized by synovial niches of autoreactive B cells. Autocrine production of B cell survival factor BAFF by RA synovial fibroblasts (RASF) supports ongoing B cell activation within the RA synovium. We investigated whether SLPI: (1)is produced by Toll-like receptors (TLRs)-treated RASF and regulates B cell activation; (2)exerts immunoregulatory effects in the RA synovium/SCID chimeric model and in collagen induced arthritis (CIA). Methods: mRNA and protein expression of SLPI in RASF/RADF (dermal) stimulated with/without TLR2/TLR3/TLR4 ligands was assessed by QT-PCR and ELISA. RASF were treated with/without recombinant SLPI to study: (1)BAFF expression; (2)AID expression and class-switching in co-culture with IgD+ B cells. BAFF expression and antibody production were examined in rSLPI-treated RA/SCID mice. Severity of arthritis, anti-CII antibodies, and joint histopathology were studied in rSLPI-treated CIA mice. Results: Stimulation of RASF with TLR3-ligands led to a 15-fold induction of SLPI mRNA. SLPI protein was time-dependently released from TLR3-stimulated RASF, but not RADF. SLPI restrained the production of BAFF, AID and IgA/G/M in TLR3-treated RASF and co-cultures, respectively. SLPI reduced BAFF expression and IgG/IgM production in RA/SCID mice while severity of arthritis, cartilage damage and anti-CII-IgG2a were reduced in SLPI-treated CIA. Conclusions: RASF release high levels of SLPI constitutively and upon TLR3 stimulation. SLPI directly modulates BAFF and B cell activation in vitro/in vivo and reduces joint inflammation in CIA, highlighting a novel endogenous anti-inflammatory pathway with therapeutic potential in RA. 071 RENAL INVOLVEMENT MORE FREQUENT AND MAY BE LINKED TO POORER SURVIVAL AMONG FILIPINO MALES WITH SLE M.A.C. Saquing1, S. Tupas1, S.V. Navarra1 1Medicine Section of Rheumatology, University of Santo Tomas, Metro Manila, Philippines Objective: To compare the organ involvement and survival of Filipino males vs. females with systemic lupus erythematosus (SLE). Methods: Retrospective study describing the survival rate of Filipino male lupus patients seen at the Rheumatology Clinics of the University of Santo Tomas (UST) Hospital, Manila, Philippines. Of the 1470 patients entered in the UST Lupus Database from 1998 - 2012, 95 (6.46%) were males. Age at SLE diagnosis, median survival rate , and causes of mortality were described. Results: Average age at diagnosis of males was 27.33 ± 12.6 years. Average disease duration was 63 ± 57 months vs. females at 99 ± 75.66 months. In males, renal involvement (58% vs 41% , p<0.0008) and hematologic manifestations (55% vs 42% , p< 0.0139) were more common, whereas arthritis (58% vs 71%, p= 0.0152) and photosensitivity (38% vs 52% p= 0.0150) were significantly less frequent. Median survival rate of males was 4 years vs 7 years for females. Of the 22 male (23%) who died , the average disease duration was 48 + 46 with renal failure (27%) and infection (27%) as the primary causes of death. Conclusion: Renal and hematologic manifestations were more common in males than females, whereas the more symptomatic musculoskeletal and cutaneous ie photosensitivity manifestations were more common in females * reinforcing the need for earlier detection and aggressive management of renal involvement especially in males with SLE. Poorer survival also appeared to be linked with renal involvement in this group of Filipino male SLE patients. 072 NATURAL KILLER AND NATURAL KILL T CELL DYSFUNCTION IN ADULT-ONSET STILL'S DISEASE Y.W. Park1, Y.N. Cho1, T.J. Kim1, H.M. Jin1, H.J. Jung1, J.Y. Kim1, M.J. Kim1, S.J. Kee2 1Rheumatology, Chonnam National University Hospital, Gwangju, Korea 2Laboratory Medicine, Chonnam National University Hospital, Gwangju, Korea Aims. To examine the levels and functions of natural killer (NK) and natural killer T (NKT) cells, investigate relationships between NK and NKT cells, and determine the clinical relevance of NKT cell levels in patients with adult-onset Still's disease (AOSD). Methods. Patients with active untreated AOSD (n=20) and age- and sex-matched healthy controls (n=20) were studied. NK and NKT cell levels were measured by flow cytometry. Peripheral blood mononulclear cells were cultured in vitro with α-galactosylceramide (α-GalCer). NK cytotoxicity against K562 cells and proliferation indices of NKT cells were estimated by flow cytometry. Results. Percentages and absolute numbers of NKT cells were significantly lower in the peripheral blood of AOSD patients than in that of healthy controls. Proliferative responses of NKT cells to α-GalCer were also lower in patients, and this was found to be due to proinflammatory cytokines and NKT cell apoptosis. In addition, NK cytotoxicity was found to be significantly lower in patients than in healthy controls, but NK cell levels were comparable in the two groups. Notably, this NKT cell deficiency was found to be correlated with NK cell dysfunction and to reflect active disease status. Furthemore, α-GalCer-medicated NK cytotoxicity, showeing the interaction between NK and NKT cells, was signficantly lower in AOSD patients than in healthy controls. Conclusions. These findings demonstrate that NK and NKT cell functions are defective in AOSD patients and suggest that these abnormalities contribute to innate immune dysfunction in AOSD 073 LOW SERUM LEVEL OF 25-HYDROXYVITAMIN D3 IN NEWLY ONSET SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: INTRINSIC ABNORMALITY? X. Zhang1, O. Jin1, Q. Wei1, H. Huang1, C. Hou1, Z. Lin1, Z. Liao1, D. Lin1, Q. Li1, J. Gu1 1Rheumatology, The Affiliated Third Hospital of Sun Yat-san University Rheumatology, Guangzhou, China OBJECTIVES: Vitamin D deficiency has been found in patients with SLE, however, whether this deficiency is due to SLE intrinsic abnormality or a result of some other reasons (such as avoidance of sunshine, photoprotection, renal insufficiency and the use of medications including glucocorticoids and HCQ) are still not clear. We aim to investigate the serum 25(OH)D levels on newly diagnosed SLE patients, further more, we want to evaluate the relationship between 25(OH)D level and the bone degradation marker (amino-terminal cross-linked telopeptide of type I collagen, ICTP) and SLE disease activity index (SLEDAI). METHODS: SLE patients were divided into 3 groups: (1) newly onset SLE (2) avtive SLE (3) stable SLE. Age and sex matched healthy donor were recruited. Both group 2 and 3 patients were given Vitamin D and Calcium to avoid GIOP. Serum levels of 25(OH)D and ICTP were measure by ELISA. RESULTS: (1) The level of 25-vitamin D in newly on-set SLE patients (32.75±3.20 nmol/L) was significantly lower than active (60.50±7.21 nmol/L) or stable (59.23±5.06 nmol/L) SLE patients and healthy donors (60.97±4.89 nmol/L) (P<0.05, respectively), while there were no differences between active, stable SLE patients and the healthy donors. No correlation was found between the level of 25-vitamin D and ICTP, or level of 25-vitamin D and SLEDAI, in healthy donors, newly on-set, active and stable SLE patients respectively. (2) The level of ICTP in newly on-set SLE patients (13.05±3.00 ug/L) and active SLE (9.23±2.59 ug/L) was significantly higher than stable SLE patients (5.13±1.14 ug/L, p=0.009). The levels of ICTP were respectively correlated with SLEDAI (newly on-set SLE: (r=0.70, p=0.016), active SLE: (r=0.83, p=0.001) and stable SLE: (r=0.59, p=0.005)). CONCLUSIONS: 1. The low level of 25-vitamin D in newly on-set SLE patients suggests that this may be an intrinsic abnormality, whose regulation to immune system is insufficient, which may contribute to the pathogenesis of SLE. After treat with Vitamin D and Calcium, both active or stable SLE reached normal 25-vitamin D level. 2. The level of ICTP in newly on-set SLE patients and active SLE patient was significantly higher than stable SLE patients, and was correlated with SLEDAI,suggesting that the inflammation of SLE may influence the bone degradation. 074 MATERNAL AND FETAL OUTCOMES OF LUPUS PREGNANCIES AMONG FILIPINO PATIENTS IN A TERTIARY HOSPITAL C. Tan1, L.R.L. Lizardo1, S.V. Navarra1 1Rheumatology, University of Santo Tomas Hospital, Manila, Philippines Background and Objective: Pregnancy poses a relevant management challenge in systemic lupus erythematosus (SLE), a disease which usually affects women of child-bearing age. Maternal and fetal outcomes were retrospectively reviewed in this study. Design: SLE patients who became pregnant after diagnosis were included. Results: There were 85 patients with 184 pregnancies occurring during the course of the disease. The mean age in years at SLE diagnosis was 26.19 while the mean age in years at pregnancy was 28.74. Majority delivered via cesarean section (54.7%) with 92.3% of infants having a normal birth weight. Pre-pregnancy co-morbidities include chronic hypertension (6.5%), Tuberculosis (TB) (2.7%) and Lupus Nephritis (LN) (9.2%). During pregnancy, maternal complications were gestational diabetes (GDM) (0.54%), pre-eclampsia (8.2%), varicella-zoster (VZV) infection (1.6%) and hyperthyroidism (0.54%). Post-pregnancy complications include pericardial effusion (0.54%), pericarditis (0.54%), dilated cardiomyopathy (0.54%), post partum depression (0.54%), and hypertension (0.54%). Among the pregnancy outcomes, term deliveries were recorded in 97 (82.9%) patients while 20 (17.1%) had preterm deliveries. There were 67 (36.4%) nonviable pregnancies manifested as miscarriages (83.6%), blighted ovum (8.9%) and intrauterine fetal demise (IUFD) (7.5%). Congenital diseases noted after delivery include congenital heart block (1.7%), meningocoele (0.86%), thyroid abnormality (0.86%), G6PD (0.86%), neonatal lupus (0.86%) and autism (0.86%). Conclusion: Although successful pregnancy outcomes are possible for SLE patients, miscarriages, preterm deliveries, blighted ovum and IUFD remain a concern, requiring close monitoring and effective multi-specialty team approach. Funding: Lupus-Inspired Advocacy Project of Rheumatology Educational Trust Foundation Inc. 075 RECOMBINANT DOMAIN V OF BETA2-GLYCOPROTEIN I INHIBITS THE FORMATION OF ATHEROGENIC OXLDL/BETA2-GLYCOPROTEIN I COMPLEXES Q.P. Liu1, Y. Chi1, J.D. Li1, R.J. Wang1, E. Matsuura2 1College of Life Science and Technology, Dalian University, Dalian, China 2Department of Cell Chemistry, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan Background: Oxidized low-density lipoproteins (oxLDL) interact with beta2-glycoprotein I (β2-GPI) to form oxLDL/β2-GPI complexes implicated as autoantigens that promote the development of atherothrombotic vascular complications in patients with antiphospholipid syndrome (APS). The region of β2-GPI responsible for the binding with oxLDL has been located in the same phospholipid-binding region of domain V (DV). Anti-oxLDL/β2-GPI antibodies enhance the in vitro macrophage uptake of oxLDL that explains the accelerated progression of autoimmune-mediated atherothrombosis. We hypothesized that DV of β2-GPI may competitively inhibit the formation of circulating oxLDL/β2-GPI complexes. Download 1.13 Mb. Share with your friends:
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