Distribution and phenotype of rotavirus-specific B cells induced during the antigen-driven primary response to 2/6 virus-like particles administered by the intrarectal and the intranasal routes.

Selection of mucosal sites is an important step in mucosal vaccine development. The intrarectal (IR) route represents an alternative to the oral route of immunization; nevertheless, immune responses induced by this route are not well defined. Here, we studied the early primary B cell response (induction, homing, and phenotype) induced by IR immunization with rotavirus (RV)-2/6 virus-like particles (VLP). Using flow cytometry, we traced RV-specific B cells in different lymphoid tissues and analyzed the expression of alpha4beta7 and CCR9, which are important receptors for homing to the gut, as well as CD5, a marker expressed by B1-a cells, which are a major source of natural antibodies. We observed a massive, specific B cell response in rectal follicles, lumbar, and mesenteric lymph nodes but not in Peyer's patches or cervical lymph nodes. A minority of cells expressed alpha4beta7, suggesting a probable lack of migration to the gut, whereas CCR9 and CD5 were expressed by 30-50% and 30-75% of specific B cells, respectively. Then, we compared the intranasal route of immunization and observed similar B cell frequency and phenotype but in respiratory lymphoid tissues. These results confirm the high compartmentalization of B cell responses within the mucosal system. They show that CCR9 expression, conversely to alpha4beta7, is not restricted to B cells induced in the gut. Finally, an important part of the RV-specific B cell response induced at the mucosal level during the primary response to VLP is most likely a result of B1-a cells.

Predictive factors of transarterial chemoembolisation toxicity in unresectable hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolisation (TACE) is an effective treatment for unresectable hepatocellular carcinoma (HCC), but can cause severe toxicity. AIM: To identify predictive factors of severe TACE-related toxicity in patients with unresectable HCC. METHODS: All HCC patients who underwent TACE at the Dijon University Hospital between 2008 and 2011 were included in this retrospective study. Severe TACE-related toxicity was defined as the occurrence of any adverse event grade ≥ 4, or any adverse event that caused a prolongation of hospitalisation of >8 days, or any additional hospitalisation within 1 month after TACE. Factors predicting toxicity were identified using a logistic regression model. The robustness of the final model was confirmed using bootstrapping (500 replications). RESULTS: 124 patients were included, median age was 67 years and 90% were male; 22 patients (18%) experienced severe TACE-related toxicity. Factors that independently predicted severe TACE-related toxicity in multivariate analysis were total tumour size (OR, 1.15 cm(-1); 95%CI, 1.04-1.26; p=0.01), and high serum AST levels (OR, 1.10 per 10 IU/l; 95%CI, 1.01-1.21; p=0.04). The results were confirmed by bootstrapping. CONCLUSIONS: Total tumour size and high serum AST levels were predictive factors of severe TACE-related toxicity in this hospital-based series of patients with unresectable HCC.