Host Genetics of Response to Hepatitis B Vaccine: A Systematic Review

Background. Hepatitis B virus (HBV) is an important cause of chronic viral disease worldwide and can be life threatening. While a safe and effective vaccine is widely available, 5 to 10% of healthy vaccinees fail to achieve a protective anti-hepatitis B surface antigen antibody (anti-HBs) titer (>10mIU/ml). A limited number of studies investigated host genetics of the response to HBV vaccine. To our knowledge, no comprehensive overview of genetic polymorphisms both within and outside the HLA system has been done so far. Aim. The aim of this study was to perform a systematic review of the literature of human genetics influencing immune response after hepatitis B vaccination. Methods. Literature searches using keywords were conducted in the electronic databases Medline, Embase and ISI Web of Science the cut-off date being March 2014. After selection of papers according to stringent inclusion criteria, relevant information was systematically collected from the remaining articles, including demographic data, number of patients, schedule and type of vaccine, phenotypes, genes and single nucleotide polymorphisms (SNPs) genotyping results and their association with immune response to hepatitis B vaccine. Results. The literature search produced a total of 1968 articles from which 46 studies were kept for further analyses. From these studies, data was extracted for 19 alleles from the human leukocyte antigen (HLA) region that were reported as significant at least twice. Among those alleles, 9 were firmly associated with vaccine response outcome (DQ2 [DQB1*02 and DQB1*0201], DR3 [DRB1*03 and DRB1*0301], DR7 [DRB1*07 and DRB1*0701], C4AQ0, DPB1*0401, DQ3, DQB1*06, DRB1*01 and DRB1*13 [DRB1*1301]). In addition, data was extracted for 55 different genes from which 13 extra-HLA genes had polymorphisms that were studied by different group of investigators or by the same group with a replication study. Among the 13 genes allowing comparison, 4 genes (IL-1B, IL-2, IL-4R and IL- 6) revealed no significant data, 6 genes (IL-4, IL-10, IL-12B, IL-13, TNFA, IFNG and TLR2) were explored with inconsistent results and 2 genes (CD3Z and ITGAL) yielded promising results as their association with vaccine response was confirmed by a replication approach. Furthermore, this review produced a list of 46 SNPs from 26 genes that were associated with immune response to vaccine only once, providing novel candidates to be tested in datasets from existing genome-wide association studies (GWAS). Conclusion. To the best of our knowledge, this is the first systematic review of immunogenetic studies of response to hepatitis B vaccine. While this work reassesses the role of several HLA alleles on vaccine response outcome, the associations with polymorphisms in genes outside the HLA region were rather inconsistent. Moreover, this work produced a list of 46 significant SNPs that were reported by a single group of investigators, opening up some interesting possibilities for further research

Cardiovascular risk assessment in people living with HIV compared to the general population

La prévention et le traitement des maladies cardiovasculaires (MCV) repose en partie sur la stratification des individus au moyen de scores de risque cardiovasculaire. Dans la pratique clinique, il est débattu de savoir quel score utiliser chez les personnes vivant avec le VIH (PVVIH), particulièrement exposés aux maladies chroniques sous l’ère des traitements antiviraux hautement efficaces. Nous avons évalué et comparé de manière prospective la performance des scores de risque cardiovasculaire chez les PVVIH et les personnes de la population générale. Nous avons également testé si l’ajout de variables spécifiques au VIH pouvait améliorer la performance des scores de risque développés pour la population générale. Le score européen Systematic COronary Risk Evaluation 2 (SCORE2), le score nord-américain Pooled Cohort Equations (PCE) et le score spécifique au HIV Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) ont été calculés chez des participants exempts de MCV entre 2003 et 2009. Au total, 6373 (âge moyen, 40,6 ans (déviation standard (DS), 9,9)) PVVIH de l’étude de cohorte suisse sur le VIH (SHCS) et 5403 (52,8 ans (DS, 10,7)) personnes de la cohorte CoLaus|PsyCoLaus ont été inclus dans l’analyse. Nous avons testé la discrimination et l’étalonnage, et calculé le Net Reclassification Improvement (NRI) après ajout de facteurs spécifiques au VIH aux scores développés pour la population générale. Respectivement 533 (8,4%) et 374 (6,9%) personnes ont développé une MCV durant des suivis moyens de 13,5 (DS, 4,1) ans dans la SHCS et de 9,9 (DS, 2,3) ans dans CoLaus|PsyCoLaus. Cela correspondait à des taux d’incidence ajustés selon l’âge de respectivement 12,9 et 7,5 pour 1000 personnes-année. Dans la SHCS, SCORE2, PCE et D:A:D présentaient des capacités discriminatives comparables (aire sous la courbe ROC (receiver operating characteristic) de 0,745 (intervalle de confiance (IC) à 95 %, IC, 0,723–0,767), 0,757 (IC à 95 %, 0,736–0,777) et 0,763 (IC à 95 %, 0,743–0,783)). L’ajout de variables spécifiques au VIH (nadir CD4 et exposition à l’abacavir) à SCORE2 et PCE a donné un NRI de respectivement -0,1 % (IC à 95 %, -1,24 à 1, P = 0,83) et de 2,7 % (IC à 95 %, 0,3 à 5,1, P = 0,03). En conclusion, les PVVIH présentent un taux deux fois plus élevé de MCV que les individus de la population générale. SCORE2 et PCE sont valides pour prédire les MCV chez les PVVIH, notamment en raison de leur ensemble de variables plus faciles à utiliser par rapport à des scores plus complexes intégrant des données spécifiques au VIH. L'ajout de facteurs spécifiques au VIH aux scores développés pour la population générale n'a pas entraîné d'amélioration cliniquement significative de leur performance

Network Inference using Sinusoidal Probing

The aim of this manuscript is to present a non-invasive method to recover the network structure of a dynamical system. We propose to use a controlled probing input and to measure the response of the network, in the spirit of what is done to determine oscillation modes in large electrical networks. For a large class of dynamical systems, we show that this approach is analytically tractable and we confirm our findings by numerical simulations of networks of Kuramoto oscillators. Our approach also allows us to determine the number of agents in the network by probing and measuring a single one of them.Comment: 5 pages, 4 figure