Objectives: Recurrent aphthous stomatitis (RAS) is a complex genetic disorder that can be triggered by several envi- ronmental factors including anxiety. The serotonin transporter gene (SLC6A4) which encodes the serotonin transporter (5-HTT) is linked to stress and regulates serotonin signaling. Furthermore, polymorphisms in SLC6A4 have been associated with a pro-in- flammatory state. The aim of this study was to investigate if there is an association between RAS and functional polymorphisms in the SLC6A4 gene. Methods: A case-control association study including 100 Jordanian RAS patients and 150 age- gender- and ethnically- matched controls was conducted. One 44 bp insertion/deletion polymorphism (5-HTTLPR) in the promoter region (rs4795541) and 4 SNPs were genotyped; rs28914828, rs1042173, rs25531 and rs28914834. Genotyping was conducted using PCR for (5- HTTLPR) and PCR-RFLP technique for all other SNPs. Asso- ciation was assessed by logistic regression analysis. Estimation of haplotype frequencies was carried out using the EH program. Results: The rs28914828, rs28914834 and rs25531 markers were not polymorphic in the Jordanian population. No significant difference in the genotype or allele distribution be- tween cases and controls was observed for rs1042173 and rs4795541. The logistic regression analysis after correcting for age, gender, smoking status, anxiety and depression revealed no significant change in the odds of having any of the genotypes for rs1042173 or rs4795541. However, the 5-HTTLPR LL genotype reduces the likelihood of having RAS by 37%. Linkage disequilibrium (LD) analysis revealed a weak LD between the 2 markers (D`¼ 0.33, P¼ 0.0002); therefore, no haplotypes were constructed. Conclusions: This is the first study to investigate the association of the SLC6A4 gene with RAS. Results from this study population indicate a lack of association with RAS. Confirmatory studies in other populations with larger sample may be warranted. BLEEDING COMPLICATIONS IN PATIENTS WITH LIVER DISEASE J. HELENIUS-HIETALA, F. ÅBERG, J.H. MEURMAN, H. ISONIEMI. HELSINKI UNIVERSITY CEN- TRAL HOSPITAL, HELSINKI, FINLAND. Objectives: Oral surgery is challenging in patients with end-stage liver disease due to coagulopathy. Platelets (PLT), fresh frozen plasma (FFP), and tranexamic acid are commonly given pre-operatively to prevent bleeding. We investigated the risk and prevalence of bleeding after tooth extraction from liver disease patients with the hypothesis that bleeding associates with platelet count and INR values. Methods: This open descriptive study included 133 adult chronic liver disease patients from Helsinki University Central Hospital, Finland, who required tooth extractions during 2000- 2006. Bleeding risk was analyzed in subgroups by platelet counts and INR level. The effect of pre-treatment administration of PLT (8-16IU), FFP (2-4IU), or tranexamic acid (1-3g PO or IV) was also tested in separate logistic regression analyses adjusted for platelet and INR levels. Results: The median number of teeth extracted was 4 (range 1-20). Ten patients (7.5%) showed post-extraction bleeding complications that needed hospital treatment; 9 had liver cirrhosis. Compared with non-bleeding patients, those with bleeding had higher median liver disease (MELD) scores (18 vs.13), INR levels (1.6 vs.1.4) and lower platelet counts (85 vs.101xE9/l), respectively (all ns.) Rates of bleeding correlated with the degree of coagulopathy but 3 patients showed bleeding despite platelet count>100xE9/l and INR<2.0. Pre-extraction administration of PLT, FFP, or tranexamic acid was paradoxically associated with increased risk of bleeding complications (OR¼4.2, 95% CI: 0.9-19.8, ns; OR¼2.8, 95% CI: 0.6-13.9, ns; OR¼7.7, 95% CI: 1.8-32.5, P ¼ 0.006; respectively). Conclusions: Tooth extractions were safely performed in most liver disease patients studied. Low platelet count and high INR level were associated with bleeding, but prophylactic transfusions to correct these abnormalities did not ensure adequate hemostasis. Prophylactic transfusions should therefore be individually evaluated, and close post-operative follow-up is warranted in this patient group. EPITOPE-DEPENDENT PATHOGENICITY OF ANTI- BODIES TARGETING A MAJOR PEMPHIGOID AUTO- ANTIGEN, BP180 M. WADA, W. NISHIE, H. UJIIE, K. IZUMI, H. IWATA, K. NATSUGA, H. SHIMIZU, Y. KITAGAWA. HOKKAIDO UNIVERSITY, SAPPORO, HOK- KAIDO, JAPAN. Objectives: Bullous pemphigoid (BP) is a major auto- immune blistering skin disorder, in which autoantibodies (autoAbs) target a hemidesmosomal transmembrane, BP180. In BP, pathogenic roles of autoAbs directing the juxtamembranous extracellular non-collagenous 16th A (NC16A) domain of BP180 have been elucidated. AutoAbs directing C-terminal regions of BP180 are thought to induce mucosal lesions including mucous membrane pemphigoid; however, the role of Abs targeting non- NC16A regions including C-terminal domain remains uncertain. The aim of this study is to address the pathogenic roles of the Abs targeting non-NC16A regions of BP180. Methods: We produced mouse IgG1 monoclonal anti- bodies (mAbs) directing the C-terminal portion (mAb C17-C1) and NC16A domain (mAb TS39-3), and compared mAb C17-C1 with mAb TS39-3. mAb C17-C1, mAb TS39-3 and normal mouse IgG1 as a control were injected intraperitoneally into neonatal human BP180-expressing transgenic (BP180-human- ized) mice and skin detachment was evaluated. Cultured normal human epidermal keratinocytes (NHEKs) were treated with mAbs C17-C1 and TS39-3 to disclose dynamics of immune complexes (ICs) on the cell surface of NHEKs. Results: Passive transfer of mAb TS39-3 directing the NC16A domain, but not mAb C17-C1 targeting the C-terminal region of human BP180, induces dermal-epidermal separation in neonatal BP180-humanized mice. Interestingly, the mAb C17-C1 strongly binds with the dermal-epidermal junctions of recipient mice skin. In NHEKs, mAb TS39-3 internalizes ICs into cyto- plasm via macropinocytosis after binding with BP180 on the cell surface, which is associated with reduction of BP180 expression. In contrast, mAb C17-C1 fails to reduce BP180, although the mAb binds with BP180 on the cell surface. Conclusions: This study shows that pathogenicity of Abs directing BP180 can be epitope-dependent, which is associated with internalization of ICs on the cell surface of basal keratino- cytes via macropinocytosis-mediated endocytosis. IL-17A AND IL-17F POLYMORPHISMS IN RHEUMA- TOID ARTHRITIS AND SJO ¨ GREN’S SYNDROME L.A. GUEIROS, C. CARVALHO, I.H. SILVA, A. BARKOKEBAS, A. DUARTE, A. CARVALHO, J.C. LEÃO. UNIVERSIDADE FEDERAL DE PERNAMBUCO, RECIFE, PERNAMBUCO, BRAZIL. ORAL MEDICINE OOOO e142 Abstracts September 2015