| 1. |
- Iorio Di, C T, et al.
(författare)
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Cross-border flow of health information: is 'privacy by design' enough? Privacy performance assessment in EUBIROD.
- 2013
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Ingår i: European Journal of Public Health. - : Oxford University Press (OUP). - 1101-1262 .- 1464-360X. ; 23:2, s. 247-53
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Tidskriftsartikel (refereegranskat)abstract
- Background: The EUBIROD project aims to perform a cross-border flow of diabetes information across 19 European countries using the BIRO information system, which embeds privacy principles and data protection mechanisms in its architecture (privacy by design). A specific task of EUBIROD was to investigate the variability in the implementation of the EU Data Protection Directive (DPD) across participating centres. Methods: Compliance with privacy requirements was assessed by means of a specific questionnaire administered to all participating diabetes registers. Items included relevant issues e.g. patient consent, accountability of data custodian, communication (openness) and complaint procedures (challenging compliance), authority to disclose, accuracy, access and use of personal information, and anonymization. The identification of an ad hoc scoring system and statistical software allowed an overall quali-quantitative analysis and independent evaluation of questionnaire responses, automated through a dedicated IT platform (‘privacy performance assessment’). Results: A total of 18 diabetes registers from different countries completed the survey. Over 50% of the registers recorded a maximum score for accountability, openness, anonymization and challenging compliance. Low average values were found for disclosure and disposition, access, consent, use of personal information and accuracy. A high heterogeneity was found for anonymization, consent, accuracy and access. Conclusions: The novel method of privacy performance assessment realized in EUBIROD may improve the respect of privacy in each data source, reduce overall variability in the implementation of privacy principles and favour a sound and legitimate cross-border exchange of high quality data across Europe.
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| 2. |
- Kis, Loránd L., et al.
(författare)
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The STAT6 signaling pathway activated by the cytokines IL-4 and IL-13 induces expression of the Epstein-Barr virus-encoded protein LMP-1 in absence of EBNA-2 : implications for the type II EBV latent gene expression in Hodgkin lymphoma
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 117:1, s. 165-174
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Tidskriftsartikel (refereegranskat)abstract
- In line with the B-lymphotropic nature of EBV, the virus is present in several types of B cell lymphomas. EBV expresses a different set of latent genes in the associated tumors, such as EBNA-1 and LMPs (type II latency) in the classical Hodgkin lymphomas (cHL). We have previously reported that exposure of the in vitro EBV-converted, HL-derived cell line KMH2-EBV to CD40-ligand and IL-4 induced the expression of LMP-1. Here we show that exposure to IL-4 or IL-13 alone induced LMP-1 in the absence of EBNA-2. The induction of LMP-1 by IL-4 and IL-13 was mediated by the signal transducer STAT6 and a newly defined high-affinity STAT6-binding site in the LMP-1 promoter. IL-4 induced LMP-1 also in Burkitt lymphoma-derived lines and in tonsillar B cells infected with the EBNA-2-deficient EBV strain P3HR-1. Furthermore, co-culture of EBV-carrying BL cells with activated CD4(+) T cells resulted in the induction of LMP-1 in the absence of EBNA-2. As the Hodgkin/Reed-Sternberg are known to secrete IL-13, to have constitutively activated STAT6, and to be closely surrounded by CD4+ T cells, these mechanisms may be involved in the expression of LMP-1 in the EBV-positive cHLs.
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| 3. |
- Rasul, Abu E., et al.
(författare)
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Simultaneous detection of the two main proliferation driving EBV encoded proteins, EBNA-2 and LMP-1 in single B cells
- 2012
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Ingår i: JIM - Journal of Immunological Methods. - : Elsevier BV. - 0022-1759 .- 1872-7905. ; 385:1-2, s. 60-70
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Tidskriftsartikel (refereegranskat)abstract
- Epstein Barr virus (EBV) is carried by almost all adults, mostly without clinical manifestations. Latent virus infection of B lymphocytes induces activation and proliferation that can be demonstrated in vitro. In healthy individuals, generation of EBV induced malignant proliferation is avoided by continuous immunological surveillance. The proliferation inducing set of the virally encoded genes is expressed exclusively in B cells in a defined differentiation window. It comprises nine EBV encoded nuclear proteins, EBNA 1-6, and three cell membrane associated proteins, LMP-1,2A and 2B, designated as latency Type III. Outside this window the expression of the viral genes is limited. Healthy carriers harbor a low number of B lymphocytes in which the viral genome is either silent or expresses one virally encoded protein, EBNA-1, latency Type I. In addition, EBV genome carrying B cells can lack either EBNA-2 or LMP-1, latency Type IIa or Type IIb respectively. These cells have no inherent proliferation capacity. Detection of both EBNA-2 and LMP-1 can identify B cells with growth potential. We devised therefore a method for their simultaneous detection in cytospin deposited cell populations. Simultaneous detection of EBNA-2 and LMP-1 was reported earlier in tissues derived from infectious mononucleosis (IM), postransplantation lymphoproliferative disorders (PTLD) and from humanized mice infected with EBV. We show for the first time the occurrence of Type IIa and Type IIb cells in cord blood lymphocyte populations infected with EBV in vitro. Further, we confirm the variation of EBNA-2 and LMP-1 expression in several Type III lines and that they vary independently in individual cells. We visualize that in Type III LCL, induced for plasmacytoid differentiation by IL-21 treatment, EBV protein expression changes to Type ha (EBNA-2 negative LMP-1 positive). We also show that when the proliferation of EBV infected cord blood lymphocyte culture is inhibited by the immunomodulator, PSK the majority of the cells express latency Type IIa pattern. These results show that by modifying the differentiation state, the proliferating EBV positive B cells can be curbed. Type IIa expression is a characteristic for EBV positive Reed-Sternberg (R/S) cells in EBV positive Hodgkin's lymphomas. For survival and proliferation, the R/S cells require the contribution of the in vivo microenvironment Consequently, Type IIa lines could not be established from Hodgkin's lymphoma in vitro. We propose that these experimental cultures can be exploited for study of the Type IIa cells.
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| 4. |
- Saghafian-Hedengren, Shanie, et al.
(författare)
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Epstein-Barr Virus Coinfection in Children Boosts Cytomegalovirus-Induced Differentiation of Natural Killer Cells
- 2013
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Ingår i: Journal of Virology. - 0022-538X .- 1098-5514. ; 87:24, s. 13446-13455
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Tidskriftsartikel (refereegranskat)abstract
- During childhood, infections with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) can occur in close temporal proximity. Active, as well as latent, CMV infection is associated with enlarged subsets of differentiated natural killer (NK) and cytotoxic T cells. How EBV infection may influence CMV-driven immune differentiation is not known. We found that EBV coinfection selectively influenced the NK cell compartment of CMV-seropositive (CMV+) children. Coinfected children had significantly higher proportions of peripheral-blood NKG2C(+) NK cells than CMV+ EBV- children. Ex vivo NK cell degranulation after target cell stimulation and plasma IL-15 levels were significantly higher in CMV+ children. EBV coinfection was related to the highest levels of plasma interleukin-15 (IL-15) and IL-12p70. Remarkably, in vitro EBV infection of peripheral blood mononuclear cells (PBMC) from EBV- CMV+ children increased NKG2C(+) NK cell proportions. A similar tendency was seen in cocultures of PBMC with EBV+ lymphoblastoid B-cell lines (LCL) and IL-15. After K562 challenge, NKG2C(+) NK cells excelled in regard to degranulation and production of gamma interferon, regardless of whether there was previous coculture with LCL. Taken together, our data suggest that dual latency with these herpesviruses during childhood could contribute to an in vivo environment supporting differentiation and maintenance of distinct NK cell populations. This viral imprint may affect subsequent immune responses through altered distributions of effector cells.
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| 5. |
- Salmon, Daniel, et al.
(författare)
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Type I interferons directly down-regulate BCL-6 in primary and transformed germinal center B cells : Differential regulation in B cell lines derived from endemic or sporadic Burkitt's lymphoma
- 2012
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Ingår i: Cytokine. - : Elsevier BV. - 1043-4666 .- 1096-0023. ; 57:3, s. 360-371
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Tidskriftsartikel (refereegranskat)abstract
- Type I interferons (IFN) exert multiple effects on both the innate and adaptive immune system in addition to their antiviral and antiproliferative activities. Little is known, however about the direct effects of type IFNs on germinal center (GC) B cells, the central components of adaptive B cell responses. We used Burkitt's lymphoma (BL) lines, as a model system of normal human GC B cells, to examine the effect of type I IFNs on the expression of BCL-6, the major regulator of the GC reaction. We show that type I IFNs, but not IFN gamma, IL-2 and TNF alpha rapidly down-regulate BCL-6 protein and mRNA expression, in cell lines derived from endemic, but not from sporadic BL. IFN alpha-induced down-regulation is specific for BCL-6, independent of Epstein-Barr virus and is not accompanied by IRF-4 up-regulation. IFN alpha-induced BCL-6 mRNA down-regulation does not require de novo protein synthesis and is specifically inhibited by piceatannol. The proteasome inhibitor mG132 non-specifically prevents, while inhibitors of alternate type I IFN signaling pathways do not inhibit IFNa-induced BCL-6 protein downregulation. We validate our results with showing that IFN alpha rapidly down-regulates BCL-6 mRNA in purified mouse normal GC B cells. Our results identify type I IFNs as the first group of cytokines that can down-regulate BCL-6 expression directly in GC B cells.
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| 6. |
- Sohlberg, Ebba, et al.
(författare)
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Cytomegalovirus-Seropositive Children Show Inhibition of In Vitro EBV Infection That Is Associated with CD8(+)CD57(+) T Cell Enrichment and IFN-gamma
- 2013
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 191:11, s. 5669-5676
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Tidskriftsartikel (refereegranskat)abstract
- EBV, a human herpesvirus, is commonly acquired during childhood and persists latently in B cells. EBV seropositivity has been connected to immunomodulatory effects such as altered T and NK cell functional responses as well as protection against early IgE sensitization; however, owing to the asymptomatic presentation during childhood little is known regarding the infection process in children of different ages. In this study, we used mononuclear cells from cord blood and from 2- and 5-y-old EBV-naive children for in vitro EBV infection. We show that the degree of EBV-induced B cell activation and expansion differs between age groups and in particular in relationship to IFN-gamma production capacity. EBV infection induced redistribution between B cell subsets with enrichment of IgD(+)CD27(+) cells (commonly referred to as non-switched memory) in infected cord blood cell cultures, and of IgD(-)CD27(+) cells (switched memory) in cell cultures from older children. We also related results to serostatus to CMV, a persistent herpesvirus that can affect differentiation status of T and NK cells. As compared with CMV- children, the EBV-induced enrichment of IgD(-)CD27(+) B cells was significantly reduced in infected cell cultures from CMV+ children. This effect was associated with high levels of IFN-gamma and frequencies of highly mature CD8(+)CD57(+) T cells in CMV+ children. Our results demonstrate that both a child's age and serostatus to CMV will have an impact on EBV-induced B cell activation and expansion, and they point to the ability of viruses with immunomodulatory functions, such as CMV, to affect immune responses within the host system.
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