To determine the most effective method of producing the acellularized xenograft heart valve leaflets, we compared pathological findings of the xenograft heart valve leaflets produced by three methods; freeze-thawing, Triton and NaCl-SDS treatment and further analyzed the pattern of endothelial cells seeded onto them. Materials and methods Two pigs were sacrificed and three pulmonary valve leaflets were harvested from each animal. They were immediately stored in a tissue preservation solution and assigned in one of the three preparation methods for acellularization. Endothelial cells from the jugular vein of a goat were isolated and seeded onto the acellularized xenograft heart valve leaflets. Light and Electron microscopic analyses were performed. Result and conclusion H & E stain showed that cells were almost absent in the leaflet treated with NaCl-SDS, while cells were partly present in the leaflets treated, one with Triton and the other Freeze-thawing. Transmission microscopic analyses showed cell-free matrix with well preserved collagen architecture under the seeded endothelial cells in the leaflets treated with NaCl-SDS. In conclusion, the valve leaflets treated with NaCl-SDS among three representative methods of acellularization of tissues (freeze-thawing, Triton X-l00, and NaCl-SDS) showed the better results than the others in terms of the efficacy of decellularization and response to endothelial cell seeding.

Background To achieve a more reliable way of transplanting cardiomyocytes, we conducted an autologous cardiomyocyte transplantation using a biodegradable scaffold, instead of a syringe injection, as a vehicle for transporting cells in an ovine myocardial infarction model. Materials and Methods A myocardial infarction was created in sheep using sequential ligation of the homonymous artery and its diagonal branch. Autologous cardiomyocytes from the right ventricular infundibulum were cultured and seeded onto a biodegradable polymer scaffold. Three months after creating myocardial infarction, the two animals were re-anesthetized and cardiomyocyte-seeded scaffolds were implanted in the infarcted area. The animals were kept alive for a further month, and then sacrificed for postmortem heart examinations. Light microscopic analysis and an immunohistochemical study for myoglobin were performed. Results On postmortem gross examinations, the polymer scaffolds were visible in the background of well-demarcated thin-walled anteroseptal myocardial infarcts. Microscopic analysis showed abundant myoglobin-stained cells between the fiber strands of the polymer scaffolds. However, there is a possibility that some of these cells might have been giant cells reacting to foreign material. Conclusion The transplantation of cultured autologous cardiomyocytes into an infarct region using a biodegradable scaffold instead of syringe injection provides another promising option for cardiomyocyte transplantation, which warrants further study.

Background:Semaphorin 4D (SEMA4D) / CD100, known as a subfamily of axonal guidance proteins, has also been reported to act as an immunoregulator in several infectious and inflammatory diseases [1]. Sjögren’s syndrome (SS) is a systemic autoimmune disease that primarily affects the exocrine glands by infiltrated lymphocytes resulting in dryness of mouth and eyes. IL-17 was reported to impair the integrity of tight junction barrier and attenuate the expression of aquaporin 5 (AQP5), causing salivary gland dysfunction in SS [2].Objectives:This study was aimed to evaluate the role of SEMA4D in patients with SS and investigate the effect of SEMA4D on human salivary gland epithelial cell (SGEC) and T cell.Methods:Soluble SEMA4D levels in plasma were measured by enzyme-linked immunosorbent assay (ELISA) from patients with SS, non-SS sicca and healthy controls. Immortalized human SGECs, originated from acini (NS-SV-AC) and duct (NS-SV-DC), were used to evaluate the effects of SEMA4D. CD4+T cells from human peripheral blood were isolated to determine the secretion of cytokines in response to SEMA4D. IFN-γ and IL-17 were used to determine the effects on AQP5 expression of SGEC.Results:The levels of soluble SEMA4D in plasma were increased in patients with SS (median [interquartile range]: 1221.3 [393.5] pg/mL) compared to non-SS sicca (940.2 [355.1] pg/mL,p= 0.006) or healthy controls (909.5 [108.0] pg/mL,p <0.0001). The levels of soluble SEMA4D in plasma were correlated with the levels of several autoantibodies including anti-SSA (Spearman’s rho = 0.358,p= 0.006), anti-SSB (rho = 0.350,p= 0.007), and anti-muscarinic receptor 3 (M3R) Ab (rho = 0.495,p< 0.001), and also correlated with total IgG (rho = 0.431,p= 0.002). SEMA4D-stimulated SGECs showed decreased expression of tight junctions such as occludin and Zo-1. CD4+T cells secreted IFN-γ (p= 0.025), IL-17 (p= 0.028), and IL-21 (p= 0.007) with SEMA4D stimulation. IFN-γ and IL-17 decreased AQP5 expression in SGECs.Conclusion:SEMA4D contributed to decreased expression of tight junction in SGECs. SEMA4D induced production of IFN-γ and IL-17 in CD4+T cells and these cytokine decreased AQP5 expression in SGECs.References:[1]Worzfeld T, Offermanns S. Nat Rev Drug Discov. 2014;13(8):603-21.[2]Bhattarai KR, Junjappa R, Handigund M, Kim HR, Chae HJ. Autoimmun Rev. 2018;17(4):376-90.Disclosure of Interests:None declared

BackgroundHigh transmissibility and immune evasion of SARS-CoV-2 Omicron variant made it dominant variant worldwide since January 2022. Before Omicron era, several studies demonstrated that autoimmune inflammatory rheumatic disease (AIIRD) patients were vulnerable to COVID-19 infection compared to general population. However, there is a lack of epidemiologic data regarding COVID-19 outbreak in patients with AIIRD in Omicron era.ObjectivesTo identify incidence rate, hospitalization rate and potential risk factors for COVID-19 outcomes in AIIRD patients during Omicron outbreak.MethodsThis study was a prospective longitudinal study from January 1 to October 31, 2022. We included patients who visited rheumatology outpatient clinic in a nationwide, tertiary referral center in South Korea. Included patients were classified into two groups (AIIRD and non-AIIRD groups) based on underlying disease. Vaccination and infection history of COVID-19 were obtained through self-report via questionnaire and data from Korea Disease Control and Prevention Agency (KDCA). Main outcome of this study was an incidence of COVID-19 infection during the observation period. Clinical factors associated with the incidence of COVID-19 infection were investigated using Cox proportional hazard model. In the final multivariable model, clinical factors that showed a relevant association (P < 0.1) with the outcome in the univariable analysis were included as covariates.ResultsA total of 1,814 patients were analyzed (AIIRD group: 1,535, non-AIIRD group: 279). The COVID-19 incidence in AIIRD group (47.6%) was higher than that reported in general population of South Korea (43.9%) and this trend was prominent in those aged < 70 years. Longitudinal change in COVID-19 incidence during the observation period showed two peaks in March and August in both groups, which was the same trend with general population. There were 30 cases of hospitalization due to COVID-19 infection, with the rate was comparable between AIIRD and non-AIIRD groups (1.7% vs. 1.5%, P = 0.970). The incidence rate of COVID-19 in the AIIRD group was comparable to that in the non-AIIRD group (47.6% vs. 44.8%, P = 0.386). In the AIIRD group, COVID-19 infection occurred less frequently in patients with old age (≥70 years) and those receiving glucocorticoid treatment. Other clinical factors such as use of DMARDs and biologics, and underlying diseases were not associated with COVID-19 incidence in the multivariable analysis. Of note, at least one COVID-19 vaccination did not lower its incidence (unadjusted HR 1.06 [95% CI 0.82-1.38]). Although patients who received booster vaccination were less likely to be infected with COVID-19 (unadjusted HR 0.79 [0.68-0.92]), this protective effect was significant only in patient younger than 70 years (Figure 1).ConclusionDuring the Omicron outbreak in South Korea, incidence of COVID-19 infection in patients with AIIRD and non-AIIRD was comparable. Immunomodulatory agents and specific rheumatic diseases did not increase the COVID-19 incidence, and booster vaccination against COVID-19 decreased the infection only in patients younger than 70 years.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Background Patients with rheumatic diseases (RD) have underlying immune dysregulation and receive long-term immunosuppressive mediations which might negatively affect the outcome of a cancer in those patients. Conversely, autoimmune cells might help eliminate the cancer cells with a better outcome in RD patients. Objectives This study was aimed at systematically investigating effects of RD on the long term outcome of four most common cancers in a retrospective cohort study. Methods A total of 167 patients with RD and cancer and 501 age-, sex-, and cancer-matched controls without RD (1:3 ratio)who received their medical care at Seoul National University Hospital from 1992 to 2012 were included in this study. Survival curves were generated using the Kaplan-Meier plots and compared using log-ranks tests. Results The mean age of patients with RD was 57.2±11.5 years old. Female was dominant (75.0%). Rheumatoid arthritis was most common with 114 (68.4%) cases, followed by dermatomyositis/polymyositis (10.8%), systemic lupus erythematosus (10.8%), systemic sclerosis (10.2%). There were 42 (25.1%) gastric, 28 (16.8%) colon, 49 (29.3%) lung, and 48 (28.7%) breast cancers. One patient had 2 cancers. There was no significant difference in 5-year (90.0 % vs. 91.2%) and 10-year survival rates (84.3% vs. 85.0%, P=0.983) between the cancer patients with RD and the controls (Figure 1). In a subgroup analysis by cancer types, 5-year (100% vs. 92.2%) and 10-year cancer survival of gastric cancer were significantly better in the RD group as compared to the control group (100%, vs. 82.8%, P=0.026), whereas those of colon, lung, and breast cancer did not differ between them. Image/graph Conclusions This study clearly demonstrates that the cancer survival was not worse in patients with rheumatic diseases despite the additional presence of underlying defective immune system and concurrent use of immunosuppressive medications. Disclosure of Interest None Declared