Multiple myeloma is a plasma cell neoplasm residing in bone marrow. Despite advances in myeloma therapies, novel therapies are required to improve patient outcomes. CD47 is highly expressed on myeloma cells and a potential therapeutic candidate for myeloma therapies. Flow cytometric analysis of patient bone marrow cells revealed that myeloma cells overexpress CD47 when compared with non-myeloma cells in 73% of patients (27/37). CD47 expression protects cells from phagocytosis by transmitting an inhibitory signal to macrophages. Here we show that blocking CD47 with an anti-CD47 monoclonal antibody increased phagocytosis of myeloma cells in vitro. In xenotransplantation models, anti-CD47 antibodies inhibited the growth of RPMI 8226 myeloma cells and led to tumor regression (42/57 mice), implicating the eradication of myeloma-initiating cells. Moreover, anti-CD47 antibodies retarded the growth of patient myeloma cells and alleviated bone resorption in human bone-bearing mice. Irradiation of mice before myeloma cell xenotransplantation abolished the therapeutic efficacy of anti-CD47 antibodies delivered 2 weeks after radiation, and coincided with a reduction of myelomonocytic cells in spleen, bone marrow and liver. These results are consistent with the hypothesis that anti-CD47 blocking antibodies inhibit myeloma growth, in part, by increasing phagocytosis of myeloma cells.

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IntroductionHelicobacter pylori infection has been implicated in the pathogenesis of various gastrointestinal, hematologic, and systemic diseases. Association between Helicobacter pylori infection and nonalcoholic fatty liver disease (NAFLD) is poorly characterised. The aim of this study was to investigate the association between H. pylori positivity with cagA status and NAFLD in the large general population.MethodsThe Third National Health and Nutrition Examination Survey (NHANES) from 1988 to 1994 was utilised in this study. NAFLD was defined by ultrasonographic detection of hepatic steatosis without other known liver diseases. Antibodies to H. pylori and cagA of participants 20 years and older were measured in using ELISA.ResultsAmong total of 5,404 participants who had results of both ultrasonography and H. pylori serology, the prevalence of NAFLD was 31.9%. The prevalence of NAFLD was higher in H. pylori positive subjects (33.5±1.79%) than in negative subjects (26.1±1.65%, p < 0.001). Compared with cagA positive group, participants with negative cagA had higher prevalence of NAFLD (31.1±2.30% vs. 36.4±2.37%, p < 0.001). Overall participants with NAFLD had higher prevalence of H. pylori positivity in multivariable analysis (Odds ratio [OR]: 1.17; 95% confidence interval [CI]: 0.95–1.43) with marginal significance. With regard to presence of cagA protein, H. pylori and cagA positivity was not associated with NAFLD (OR: 1.05; 95% CI: 0.81–1.37) but, cagA negative H. pylori positivity was significantly associated with NAFLD in multivariable analysis (OR: 1.30; 95% CI: 1.01–1.67).ConclusionThe prevalence of NAFLD was higher in H. pylori positive subjects than in negative subjects. Especially, cagA negative H. pylori positivity was significantly associated with NAFLD, independent of other known factors in the general population.References1 Ong JP, Younossi ZM. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis 2007;11:1–16, vii.2 Kim D, Kim WR, Kim HJ, Therneau TM. Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology 2013;57:1357–65.3 Chung GE, Kim D, Kim W, et al. Non-alcoholic fatty liver disease across the spectrum of hypothyroidism. J Hepatol 2012;57:150–6.Disclosure of InterestNone Declared

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