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Le Touquet – Paris-Plage, France

Lagresle-Peyrou C.,French Institute of Health and Medical Research | Millili M.,Center Dimmunologie Of Marseille Luminy | Millili M.,French Institute of Health and Medical Research | Millili M.,French National Center for Scientific Research | And 14 more authors.
Journal of Allergy and Clinical Immunology

Background Expression of the pre-B-cell receptor (pre-BCR) by pre-BII cells constitutes a crucial checkpoint in B-cell differentiation. Mutations that affect the pre-B-cell receptor result in early B-cell differentiation blockades that lead to primary B-cell immunodeficiencies. BLNK adaptor protein has a key role in the pre-B-cell receptor signaling cascade, as illustrated by the abnormal B-cell development in the 4 patients with BLNK gene defects reported to date. However, the BLNK protein's precise function in human B-cell differentiation has not been completely specified. Methods B-cell development, including IgVH and Vk chain repertoires analysis, was studied in the bone marrow of a new case of BLNK deficiency in vitro and in vivo. Results Here, we report on a patient with agammaglobulinemia, with a total absence of circulating B cells. We detected a homozygous mutation in BLNK, which leads to the complete abrogation of BLNK protein expression. In the bone marrow, we identified a severe differentiation blockade at the pre-BI- to pre-BII-cell transition. IgVH gene rearrangements and selection of the IgH repertoire were normal, whereas the patient's pre-BI cells showed very restricted usage of the IgVκ repertoire. Complementation of bone marrow progenitors from the patient with the BLNK gene and transplantation into NOD/SCID/γcko mice allowed the complete restoration of B-cell differentiation and a normal usage of the IgVκ genes. © 2014 American Academy of Allergy, Asthma and Immunology. Source

Burgard M.,Laboratoire Of Virologie | Blanche S.,Unite Dimmunologie | Blanche S.,University of Paris Descartes | Jasseron C.,French Institute of Health and Medical Research | And 11 more authors.
Journal of Pediatrics

Objective: To compare performance of testing for human immunodeficiency virus (HIV)-1 DNA and HIV-1 RNA for diagnosis of HIV-1 infection in infants receiving preventive antiretroviral therapy. Study design: This substudy of the French multicenter prospective cohort of neonates born to HIV-infected mothers, included 1567 infants tested for HIV with polymerase chain reaction (PCR) in a single laboratory, receiving post-natal prophylaxis, not breastfed, and having simultaneous HIV-1 DNA and RNA results before 45 days. The performance of PCR was assessed in reference to the 6-month HIV-1 RNA result. Results: Specificity of both HIV-1 RNA and HIV-1 DNA PCR was 100% at all ages (except 99.8% for DNA at birth); sensitivity was 58% (RNA) and 55% (DNA) at birth, and 89% at 1 month, 100% at 3 months for both, and 100% at 6 months (DNA). Concordance between HIV-1 DNA and RNA results was 0.78 and 0.81 (Kappa) at birth and 1 month and 100% at 3 and 6 months. Type of maternal and neonatal prophylaxis had no effect on sensitivity, but influenced viral load. Conclusion: The performances of testing for HIV-1 DNA and RNA were similar with 100% sensitivity at 3 months. At 1 month during prophylaxis, 11% of infected children had negative PCR results. Copyright © 2012 Mosby Inc. All rights reserved. Source

Frange P.,Unite Dimmunologie | Frange P.,Laboratoire Of Virologie | Frange P.,University of Paris Descartes | Briand N.,French Institute of Health and Medical Research | And 11 more authors.
Pediatric Infectious Disease Journal

Background: Lopinavir/ritonavir (LPV/r) is now the protease inhibitor regimen of choice in the first-line antiretroviral therapy for children <6 years of age. Methods: We included all the human immunodeficiency virus (HIV) type 1-infected highly active antiretroviral therapy (HAART)-naive children who started an LPV/r-based regimen between 2000 and 2009 at the Necker Hospital (Paris, France). Virologic failure (VF) was defined as an HIV-RNA 50 copies/mL. Resistance genotypic test was performed in case of VF. Results: A total of 43 children were included at a median age of 4.8 years (1.8-8.0). Median level of HIV RNA and percentage of CD4 cell count was 5.5 log10 copies/mL (4.6-6) and 15% (8-27.5), respectively. HAART included LPV/r and 2 nucleoside reverse-transcriptase inhibitors, mainly lamivudine (3TC), zidovudine, and/or abacavir. The median follow-up period was 36 months (18-72). Less than 50 copies/mL of HIV RNA was observed in 46%, 67%, and 70% of the children at months 6, 9, and 12, respectively. In all, 20 children (46.5%) experienced a VF. The risk factors of primary VF were a young age and a low socioeconomic status. The genotypic resistance test, performed for 18 of 20 children with VF, revealed 1 LPV/r-resistant virus and protease inhibitor-related major mutations without LPV/r resistance in 2 other children. Of the 18 children with VF, 15 received a 3TC-based HAART: 12 of 15 (80%) harbored a 3TC-resistant virus. No virus resistant to zidovudine or abacavir was found. Conclusion: In all, 70% of HAART-naive children had virologic success at month 12. The selection of LPV-resistant strains was a rare event. A high rate of selection of 3TC-mutations strengthens the recommendation to prefer a first-line 3TC-sparing regimen, particularly for children with risk factors of poor adherence. © 2011 Lippincott Williams & Wilkins. Source

Frange P.,Unite Dimmunologie | Frange P.,University of Paris Descartes | Chaix M.-L.,University of Paris Descartes | Chaix M.-L.,Laboratoire Of Virologie | And 3 more authors.
Pediatric Infectious Disease Journal

We describe 48 cases of HIV-1-infected children newly diagnosed in 2006 to 2012 in France. Native French children were born to women whose HIV testing were mostly missed (13.6%), offered late (9.1%) or negative at start of pregnancy and not subsequently reoffered (54.5%). HIV testing of immigrant children were performed late after arrival, despite prompt access to healthcare structures. HIV testing strategies need to be improved. Copyright © 2013 by Lippincott Williams & Wilkins. Source

Frange P.,Unite Dimmunologie | De Latour R.P.,Service dHematologie greffe | Boddaert N.,Service de Radiologie Pediatrique | Oualha M.,Service de Reanimation Polyvalente Pediatrique | And 8 more authors.
Journal of Clinical Microbiology

We report two cases of adenoviral meningoencephalitis in children following allogeneic stem cell transplantation. These cases showed four similarities: isolated neurological involvement, infiltrating hyperintensities next to the third ventricle on the cerebral magnetic resonance image, the absence of concomitant detectable adenoviral viremia, and a severe clinical outcome. Copyright © 2011, American Society for Microbiology. All Rights Reserved. Source

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