Éditeur(s) : HAL CCSD BMJ Publishing Group
Résumé : International audience
BACKGROUND: Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been identified in families with autosomal dominant Parkinson's disease (ADPD), the most common of which is the p.G2019S substitution that has been found at varying frequencies worldwide. Because of the size of the LRRK2 gene, few studies have analysed the entire gene in large series of ADPD families. METHODS: We performed extensive mutation analyses of all 51 coding exons of the LRRK2 gene in index cases from 226 Parkinson's disease families compatible with autosomal dominant inheritance, mostly from France (n = 182) and North Africa (n = 14). RESULTS: We found 79 sequence variants, 29 of which were novel. Eight potentially or proven pathogenic mutations were found in 22 probands (9.7%). There were four novel amino acid substitutions that are potentially pathogenic (p.S52F, p.N363S, p.I810V, p.R1325Q) and two novel variants, p.H1216R and p.T1410M, that are probably not causative. The common p.G2019S mutation was identified in 13 probands (5.8%) including six from North Africa (43%). The known heterozygous p.R1441H and p.I1371V mutations were found in two probands each, and the p.E334K variant was identified in one single patient. Most potentially or proven pathogenic mutations were located in the functional domains of the Lrrk2 protein. CONCLUSION: This study leads us to conclude that LRRK2 mutations are a common cause of autosomal dominant Parkinson's disease in Europe and North Africa.
ISSN: 0022-2593

inserm-00529272
http://www.hal.inserm.fr/inserm-00529272
DOI : 10.1136/jmg.2008.062612
PUBMED : 19357115

Éditeur(s) : HAL CCSD Oxford University Press (OUP)
Résumé : International audience
BACKGROUND: Human immunodeficiency virus (HIV)-infected patients have decreased immune response to vaccines. Few data are available about pandemic flu vaccination in this population. METHODS: We conducted a multicenter, patient-blinded, randomized trial in a cohort of HIV-infected adults. Patients received 2 injections 21 days apart of a AS03(A)-adjuvanted H1N1v vaccine containing 3.75 μg hemagglutinin (HA) or a nonadjuvanted H1N1v vaccine containing 15 μg HA to assess hemagglutination inhibition (HI) response and safety. RESULTS: A total of 309 patients were randomized, and 306 were vaccinated. After the first vaccine dose, HI titers ≥1:40 were observed in 93.4% of the patients in the adjuvanted group (A group) (n = 155) and in 75.5% in the nonadjuvanted group (B group) (n = 151) (P < .001); seroconversion rates were 88.8% and 71.2%, and factor increases in geometric mean titers (GMT) of 21.9 and 15.1, respectively. After 2 injections, 98.6% of patients of the A group and 92.1% of the B group demonstrated HI titers ≥1:40 (P = .018); seroconversion rates were 96.5% and 87.1%, respectively, and factor increases in GMT were 45.5 and 21.2, respectively. The majority of adverse events were mild to moderate in severity; no impact on CD4+ cell count or viral load has been detected. CONCLUSIONS: In HIV-1-infected adults, the AS03(A)-adjuvanted H1N1v vaccine yielded a higher immune response than did the nonadjuvanted one, with no impact on HIV infection.
ISSN: 0022-1899

hal-00875299
https://hal.archives-ouvertes.fr/hal-00875299
DOI : 10.1093/infdis/jir211
PUBMED : 21628666

Éditeur(s) : HAL CCSD Lippincott, Williams & Wilkins
Résumé : International audience
OBJECTIVE: In immunocompromised patients, alternative schedules more immunogenic than the standard influenza vaccine regimen are necessary to enhance and prolong vaccine efficacy. We previously reported that the AS03A-adjuvanted 2009 A/H1N1v vaccine yielded a higher short-term immune response than the nonadjuvanted one in HIV-1-infected adults. This study reports the long-term persistence of the immune response. DESIGN AND METHODS: In a prospective, multicenter, randomized, patient-blinded trial, two doses of AS03A-adjuvanted H1N1v vaccine containing 3.75 μg haemagglutinin (n = 155; group A) or nonadjuvanted H1N1v vaccine containing 15 μg haemagglutinin (n = 151; group B), were administered 21 days apart. Haemagglutination inhibition and neutralizing antibodies were assessed 6 and 12 months after vaccination. RESULTS: In group A and B, the seroprotection rates were 83.7 and 59.4% at month 6, and 70.4 and 49.3 at month 12, respectively. In a multivariate analysis, persistence of seroprotection 12 months after vaccination was negatively associated with current smoking (odds ratio = 0.6, P = 0.03) and positively related with the AS03A-adjuvanted H1N1v vaccine (odds ratio = 2.7, P = 0.0002). CONCLUSION: In HIV-1-infected adults, two doses of adjuvanted influenza vaccine induce long-term persistence of immune response up to 1 year after vaccination.
ISSN: 0269-9370

hal-00875148
https://hal.archives-ouvertes.fr/hal-00875148
DOI : 10.1097/QAD.0b013e328359f27a
PUBMED : 23018437