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PubMed | Service de Parasitologie Mycologie., Unite dImmunologie, University of Burgundy, Unite de Parasitologie Mycologie and 3 more.
Type: Journal Article | Journal: Open forum infectious diseases | Year: 2016

Background. Early diagnosis and treatment are crucial in invasive fungal diseases (IFD). Serum (1-3)--d-glucan (BG) is believed to be an early IFD marker, but its diagnostic performance has been ambiguous, with insufficient data regarding sensitivity at the time of IFD diagnosis (TOD) and according to outcome. Whether its clinical utility is equivalent for all types of IFD remains unknown. Methods. We included 143 patients with proven or probable IFD (49 invasive candidiasis, 45 invasive aspergillosis [IA], and 49 rare IFD) and analyzed serum BG (Fungitell) at TOD and during treatment. Results. (1-3)--d-glucan was undetectable at TOD in 36% and 48% of patients with candidemia and IA, respectively; there was no correlation between negative BG results at TOD and patients characteristics, localization of infection, or prior antifungal use. Nevertheless, patients with candidemia due to Candida albicans were more likely to test positive for BG at TOD (odds ratio = 25.4, P = .01) than patients infected with other Candida species. In 70% of the patients with a follow-up, BG negativation occurred in >1 month for candidemia and >3 months for IA. A slower BG decrease in patients with candidemia was associated with deep-seated localizations (P = .04). Thirty-nine percent of patients with rare IFD had undetectable BG at TOD; nonetheless, all patients with chronic subcutaneous IFD tested positive at TOD. Conclusions. Undetectable serum BG does not rule out an early IFD, when the clinical suspicion is high. After IFD diagnostic, kinetics of serum BG are difficult to relate to clinical outcome.


PubMed | Groupe Hospitalier Saint Pierre, Lyon University Hospital Center, Limoges University Hospital Center, Service de Nephrologie Pediatrique and 11 more.
Type: | Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | Year: 2015

Data on anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis are scarce in children. The current study is aimed at describing the clinical features and outcomes of childhood-onset ANCA-associated vasculitis (AAV).We conducted a retrospective French multicentre study involving patients in whom AAV was diagnosed before the age of 18 years. Inclusion criteria were (i) granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) according to classification criteria of the European League Against Rheumatism/Paediatric Rheumatology European Society, and (ii) ANCA positivity. Patient and renal survival were analysed.Among 66 children included, 80% were female, 42% had GPA and 58% MPA including renal-limited vasculitis, 67% were pANCA+ and 33% cANCA+. The mean incidence of reported cases increased to 0.45 per million children/year in the period 2006-10. Median age at diagnosis was 11.5 years, and median time to diagnosis was 1 month. Initial symptoms included fever and fatigue (79%), skin lesions (41%), arthritis (42%), pulmonary (45%) and renal involvement (88%). Clinical features were similar between GPA and MPA with the exception of upper airway impairment (28%) specific of GPA. Ninety percent of the patients achieved remission after induction treatment. After a median follow-up of 5.2 years, 4 patients (6%) died, corresponding to a mortality rate of 1.2 per 100 person-years, and 22 patients (34%) developed end-stage renal disease (ESRD). Renal survival was 74, 70 and 59% at 1, 5 and 10 years, respectively. In a multivariable Cox regression model, baseline glomerular filtration rate, ethnic origin, histopathological classification and era of treatment were associated with the occurrence of ESRD. Relapse-free survival was 57% at 5 years and 34% at 10 years of follow-up. Patient and renal outcome did not significantly differ between GPA and MPA.Childhood-onset AAV is a rare disease characterized by female predominance, delayed diagnosis, frequent renal impairment and a high remission rate. Baseline GFR and new histopathological classification system are strong predictors of ESRD. Renal survival in childhood AAV has improved over time.


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 | Year: 2012

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.


Frange P.,Unite dImmunologie | De Latour R.P.,Service dHematologie Greffe | Arnaud C.,Center Hospitalier Intercommunal | Boddaert N.,Service de Radiologie Pediatrique | And 10 more authors.
Journal of Clinical Microbiology | Year: 2011

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.


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 | Year: 2014

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.


Frange P.,University of Paris Descartes | Briand N.,French Institute of Health and Medical Research | Veber F.,Unite dImmunologie | Moshous D.,Unite dImmunologie | And 8 more authors.
AIDS | Year: 2012

Objective: The risk of virologic failure and selection of resistant strains remains a challenge in HIV-1 perinatally infected children. HIV-1 coreceptor usage was determined in HAART-failing children followed in Necker Hospital (Paris, France) in order to estimate the proportion of these patients who may benefit from CCR5-antagonists therapy. Methods: HIV-1 coreceptor usage was determined with the SVMGeno2pheno10% algorithm in 51 children with virologic failure after a median treatment exposure of 7.8 years. Results: CXCR4-tropic strains were found in 31.4% of the patients. CXCR4 usage was associated with high HIV-1 DNA (P=0.01), old age (P=0.02), long ART cumulative exposure (P=0.006), and previous exposure to high number of different drugs (P=0.03) and ART combinations (P=0.03) in univariate analysis. Selection of resistant viruses and current exposure to a darunavir-based HAART tended to be more frequent in the CXCR4 group compared with the children infected with CCR5-tropic strains (P=0.06). In multivariate analysis, CXCR4 usage was exclusively correlated with HIV-1 DNA (P=0.03), which accurately reflects the cumulative exposure to viral replication over the whole duration of HIV infection. Conclusion: Two-thirds of HAART-failing children could benefit from CCR5 antagonists-based strategies, even in case of triple-class virologic failure. Such therapy should be discussed more appropriately at early stages of infection, when CCR5-tropic strains are most frequently isolated. However, before considering such strategies, further studies are needed to evaluate the efficacy and the tolerability of CCR5 antagonists in this pediatric population. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


PubMed | Limoges University Hospital Center, Unite dImmunologie, Institute Cancerologique Of La Loire, Hopital Trousseau and 6 more.
Type: Journal Article | Journal: Joint, bone, spine : revue du rhumatisme | Year: 2015

To assess the prognostic impact of clinical presentation in children with polyarteritis nodosa (PAN).Children diagnosed between 1986 and 2006 in a tertiary care pediatric rheumatology center were classified as cutaneous PAN (group 1), cutaneous PAN with significant extra-cutaneous features (group 2) or visceral childhood PAN (group 3).(1) clinical remission off-therapy at last follow-up, (2) requirement and length of glucocorticoid therapy, (3) presence of disease-related sequelae.Twenty-nine children were included. Sixteen met the Ankara criteria for PAN. Nine patients were qualified as group 1, 11 as group 2, and 9 as group 3. At last follow-up, 15 children were in clinical remission off-therapy: 4 from group 1 (44%), 4 from group 2 (36%) and 7 from group 3 (78%). Glucocorticoid therapy was required for 8 (89%), 7 (64%) and 7 (78%) patients from groups 1, 2 and 3, respectively. Seven children did not require any glucocorticoid therapy. Time-dependent probability of achieving glucocorticoid-free clinical remission was similar between the three groups. Three patients (one from each group) had digital ischemia leading to amputation. There were no significant between-group differences in outcome based on the three outcome measures addressed.Outcome was not strikingly predictable from initial presentation in children with PAN. The organ distribution-based distinction between cutaneous and visceral PAN had little prognostic power in this series.


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 | Year: 2014

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.


PubMed | Unite dimmunologie, Grenoble University Hospital Center and French Institute of Health and Medical Research
Type: Case Reports | Journal: Archives de pediatrie : organe officiel de la Societe francaise de pediatrie | Year: 2016

Malignant infantile osteopetrosis is a rare congenital disease characterized by a dysfunction of osteoclasts followed by an abnormal bone densification. We report the case of a 5-month-old infant in whom this disease was suspected because of the clinical (hepatosplenomegaly, gingival hypertrophy), hematological (pancytopenia and hypocalcemia), and radiological criteria (abnormal bone density, periosteal reaction). The genetic investigation confirmed the diagnosis. Compound heterozygous mutations in the CLCN7 gene were identified, including an as yet undescribed mutation. The second mutation had already been described as being responsible for severe and irreversible neurological damage in patients with osteopetrosis. Since this patient presented severely delayed development, he was not eligible for bone marrow transplantation.


PubMed | Aix - Marseille University, Unite dImmunologie and University of Paris Descartes
Type: Case Reports | Journal: The Journal of allergy and clinical immunology | Year: 2014

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 proteins precise function in human B-cell differentiation has not been completely specified.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.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 patients pre-BI cells showed very restricted usage of the IgV repertoire. Complementation of bone marrow progenitors from the patient with the BLNK gene and transplantation into NOD/SCID/cko mice allowed the complete restoration of B-cell differentiation and a normal usage of the IgV genes.

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