Valérie Guérin

Assistance Publique – Hôpitaux de Paris, Lutetia Parisorum, Île-de-France, France

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Publications (13)36.31 Total impact

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    ABSTRACT: BACKGROUND: We report a 7-year-old boy with high-degree steroid-dependent idiopathic nephrotic syndrome (SDNS) who went into remission with rituximab (RTX) maintenance therapy. CASE-DIAGNOSIS/TREATMENT: Four months after this patient received his first RTX infusion, there was a progressive and sustained decrease of immunoglobulin (Ig)G and IgM levels. Thirteen months after the initiation of RTX therapy he was in sustained remission without any steroid or oral immunosuppressive therapy; however, B cell depletion was still present. At this time he developed a fulminant myocarditis due to enterovirus. Despite aggressive treatment and the administration of intravenous polyvalent immunoglobulins there was no clinical improvement. He successfully underwent heart transplant surgery. CONCLUSIONS: We conclude that B cell depletion with RTX is efficacious in the treatment of paediatric SDNS but that it may be associated with severe infectious complications. Therefore, we recommend a close monitoring of Ig levels in children who have received RTX therapy and a supplementation with intravenous Ig as soon as the Ig levels fall below the lower limit of the normal range.
    Pediatric Nephrology 05/2013; 28(9). DOI:10.1007/s00467-013-2485-9 · 2.88 Impact Factor
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    ABSTRACT: Rituximab (RTX) is a new treatment strategy in high-degree steroid-dependent idiopathic nephrotic syndrome (SDNS) in childhood. Thirty patients (nine girls) with SDNS with steroid side effects and previously treated with immunosuppressive drugs, mostly calcineurin inhibitors, were treated with RTX and included in this non-controlled single-centre study. Patient age at first RTX infusion was 12.9 ± 0.7 years. Our aim was to evaluate disease outcome after a minimum CD19 depletion period of 15 months obtained by repeated RTX infusion. Minimum follow-up after initial CD19 depletion was 24 months. During the RTX treatment period, seven patients had nephrotic syndrome relapses, six among them at the time of an intermittent CD19 recovery and one patient relapsed under CD19 depletion. The risk for these patients to relapse after the RTX treatment period was higher than in those without intermittent relapses. After definitive CD19 recovery over a follow-up of 17.4 ± 1.9 months, 19 patients (63%) did not relapse and 11 (37%) relapsed 4.3 ± 1 months after defininitive CD19 recovery. Among these 11 patients, 6 already had intermittent relapses during the RTX treatment period. Steroid and immunosuppressive treatment could be discontinued in all patients during CD19 depletion and was re-introduced in two after CD19 recovery. Fourteen patients had mostly benign and transitory side effects, which did not require RTX discontinuation. In conclusion, RTX treatment with a 15-month CD19 depletion period induced long-term remission after definitive CD 19 recovery in almost two-thirds the of patients without oral immunosuppressive drugs.
    Nephrology Dialysis Transplantation 08/2011; 27(3):1083-9. DOI:10.1093/ndt/gfr405 · 3.49 Impact Factor
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    ABSTRACT: Age-related changes in memory CD4 T cells (CD4) are poorly known. To address this issue, CD4 proliferative and cytokine responses to an anti-CD3 monoclonal (CD3), to cytomegalovirus (CMV), and to adenovirus (AdV) were assessed in 57 children (age, 0.07-17.16 y) and 17 adults. Results showed i) accumulation of memory CD4 with aging, with 2-3 times more central-memory T cell (TCM; CD45RA/CD62L) than effector-memory T cell (TEM; CD45RA/62L) CD4 at any age. ii) In children older than 2 y, CMV-specific CD4-secreting IFNγ alone predominated over CD4-secreting IL2 + IFNγ and a continuous increase, with aging, in IFNγ responses to the virus was observed. In contrast, in AdV infection, CD4-secreting IL2 + IFNγ predominated and IFNγ responses to the virus reached adult levels from 3 y of age. iii) In children aged 0-2 y, lower total IFNγ responses to CMV (p < 0.02), AdV (p = 0.05), and CD3 (p < 0.01) and lower IFNγ + IL2-responses (p = 0.1, p < 0.02, p < 0.05, respectively) contrasted with no decrease in CD4-secreting IFNγ alone. Defective proliferative responses to AdV (p = 0.03) were also observed. In conclusion, the development of memory CD4 differed in acute AdV and persistent CMV infections. Young age seemed to depress mostly polyfunctional (IL2 + IFNγ secreting) CD4 in both infections.
    Pediatric Research 11/2010; 69(2):106-11. DOI:10.1203/PDR.0b013e318204e469 · 2.84 Impact Factor
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    ABSTRACT: Les infections à adénovirus sont redoutées en allogreffe de CSH pédiatrique. Mieux comprendre et mieux suivre la restauration de l’immunité spécifique anti-AdV est essentiel. Matériel et Méthodes Suivi prospectif clinico-biologique pendant 12 mois de 40 patients pédiatriques allogreffés après conditionnement myéloablatif. Suivi hebdomadaire de la PCR AdV dans le sang durant au moins 3 moi, suivi de la reconstitution T-CD4+ spécifique en CMF et par TTL. Comparaison à 34 enfants et 31 adultes sains. Résultats 38/40 patients n’ont présenté ni virémie ni infection à AdV. 32/38 (84 %) ont eu une reconstitution immunitaire anti-AdV caractérisée notamment par des taux de T-CD4+ sécréteurs d’IFNg en moins de 6 mois comparables aux témoins: 1,5 cellules/microl [0,05-8,2] chez les greffés vs 1,2 cell/ microl [0,56-2,4]. 2/40 patients ont développé une infection digestive sévère à AdV à J73 et J75 post greffe, respectivement. Aucun n’avait de reconstitution anti-AdV. Les enfants sains ont un profil similaire aux adultes tant en terme de prolifération que de pourcentages de T-CD4+ sécréteurs d’IFNg. Ces CD4+ sont essentiellement des T-CD4+ polyfonctionnels sécréteurs d’IFNg et d’IL2. Conclusion la confirmation de ces résultats devrait permettre de mieux identifier les patients à risque.
    Archives de Pédiatrie 06/2010; 17(6):4-4. DOI:10.1016/S0929-693X(10)70230-X · 0.41 Impact Factor
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    ABSTRACT: Although most patients with idiopathic nephrotic syndrome (NS) respond to steroid treatment, development of steroid dependency may require a long-term multidrug therapy including steroid and calcineurin inhibitor. Rituximab was shown to allow a reduction of the doses of steroid and immunosuppressive drugs in those patients. In the present series, 22 patients with steroid-sensitive, but steroid-dependent nephrotic syndrome were treated with rituximab. Rituximab reduced B cell count down to an undetectable level in all patients. A second treatment was necessary in 18 patients in order to maintain B cell depletion for up to 18 months. B cell depletion lasted 4.9 to 26 months (mean 17.2 months). At last follow-up, 9 patients were in remission without oral steroid or calcineurin inhibitor, although B cell count had recovered for 2.9 to 17 months (mean 9.5 months). A remission under ongoing B cell depletion was observed in 10 other patients in the absence of oral steroid or calcineurin inhibitor. Rituximab failed in 2 patients and 1 refused any additional treatment, despite B cell recovery and relapse. Toxicity of rituximab was limited to reversible cytokine shock in 2 patients and reversible neutropenia in 1 patient. No severe infection was observed.
    Pediatric Nephrology 03/2010; 25(6):1109-15. DOI:10.1007/s00467-010-1465-6 · 2.88 Impact Factor
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    ABSTRACT: CD4(+) T-cell functions that best correlate with CMV control were evaluated by studying the relationship between CMV infection and CMV-specific immune recovery as determined by proliferation assay and intracytoplasmic-IFNgamma assay. A total of 30 children (mean age: 8.30 years) who received an allogeneic hematopoietic SCT (HSCT) were included. In total, 13 recipients were seronegative before HSCT. None developed CMV infection or CMV-specific immunity. A total of 17 recipients were seropositive: (i) four patients spontaneously controlled CMV. The median of CMV-specific IFNgamma-secreting CD4 T cells was 9.13/microl at month 3 in these four patients and three of the four patients evidenced optimal proliferative responses since month 1; (ii) in 10 patients who received anti-CMV chemotherapy because of prolonged viremia, lower (P=0.016) IFNgamma responses (0.39/microl), together with delayed and/or depressed proliferative responses, were observed; (iii) finally, one patient with early CMV-associated disease had undetectable proliferative and IFNgamma responses until month 3. In conclusion, both intense IFNgamma responses and early proliferative responses seem to be associated with optimal CMV control.
    Bone marrow transplantation 08/2009; 45(3):442-9. DOI:10.1038/bmt.2009.179 · 3.47 Impact Factor
  • Transplantation 12/2008; 86(9):1322-3. DOI:10.1097/TP.0b013e318188ac0c · 3.78 Impact Factor
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    ABSTRACT: The mechanisms responsible for the increased susceptibility of fetuses to cytomegalovirus (CMV) were studied by comparing CD8(+) T cell responses to the virus in susceptible fetuses to those in their comparatively more resistant mothers. Included in the study were 16 transmitter mothers who underwent seroconversion during the first trimester of pregnancy as well as their fetuses, who were positive for CMV in amniotic fluid by polymerase chain reaction at 17-19 weeks of gestation. Fetal and maternal blood samples were collected between the 22nd and 39th week of gestation. Cytotoxic T lymphocytes (CTLs) that had activated (HLA-DR(+)), effector/memory (CD28(-)), and memory (CD18(high)) phenotypes; that stained with the HLA-A2/pp65 or the HLA-B7/pp65 multimer; and that secreted interferon (IFN)- gamma were enumerated by flow cytometry. Viral loads were determined simultaneously. The results showed (1) similar levels of activated, effector/memory, and memory CTLs in fetuses and mothers but a smaller pp65-specific CTL pool in fetuses (median, 0.015% vs. 0.99%; P=.003); (2) similar percentages of CTLs secreting IFN- gamma after stimulation with ionomycin/phorbol myristate acetate in fetuses and mothers but lower percentages of CTLs secreting IFN- gamma after stimulation with a CD3 monoclonal antibody in fetuses (median, 1% vs. 14%; P=.01); and (3) higher viral loads (mean, 17,290 vs. <250 genome equivalents/mL) in fetuses. Impaired viral clearance might be related to a defective expansion of the pp65-specific CTL pool and/or to the immaturity of IFN- gamma -secreting cells in fetuses.
    The Journal of Infectious Diseases 11/2007; 196(7):1033-43. DOI:10.1086/521196 · 5.78 Impact Factor
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    ABSTRACT: The distribution of human leukocyte antigen (HLA)-DRB1-DQA1-DQB1 haplotypes was analyzed separately in two distinct French ethnic groups with type I diabetes (T1D), i.e. French North African migrants (n= 64, mean age at diagnosis = 8.25 years) and ancient French natives (n= 60, mean age at diagnosis = 7.42 years). HLA associations were determined by calculating odds ratios (ORs) between patients and two ethnic-matched control populations. Results show highly similar ORs for the conservative DRB1*0301-DQA1*0501-DQB1*0201 haplotype of susceptibility (OR: 3.22 and 3.93 in migrants and natives, respectively) and the DRB1*1501-DQA1*0102-DQB1*0602 haplotype of resistance (OR: 0.05 and 0.03, respectively). In contrast, among the more variable DRB1*04-DQB1*0302 haplotypes of susceptibility, the DRB1*0402 (OR: 3.10 and 32.84) and 0405 (OR: 5.90 and 16.25, respectively) were associated with T1D in migrants and natives, whereas an increase of DRB1*0401, a rare allele in migrants, was significant in natives only. Also, among the DRB1*11-DQA1*0505-DQB1*0301 haplotypes of resistance, the OR observed for DRB1*1104-DQA1*0505-DQB1*0301, common in migrants, was lower (OR: 0.08) than for DRB1*1101-DQA1*0505-DQB1*0301 (OR: 0.32), common in natives. How DRB1*11 subtypes might affect differently the risk conferred by DQA1*0505-DQB1*0301 will be discussed.
    Tissue Antigens 10/2007; 70(3):214-8. DOI:10.1111/j.1399-0039.2007.00878.x · 2.35 Impact Factor
  • European Journal of Paediatric Neurology 07/2007; 11(4):247-248. DOI:10.1016/j.ejpn.2007.03.004 · 1.93 Impact Factor
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    ABSTRACT: Subacute sclerosing panencephalitis (SSPE) is a progressive, fatal neurological disorder of childhood and early adolescence. It is caused by a persistent measles virus infection of the brain without any available treatment to date. The physiopathology of the disease is largely unknown. Considering the potential role of humoral immunity in the pathogenesis of SSPE, one patient was given compassionate anti-CD20 antibodies. However, disease progression under treatment led to reconsider B cell involvement in this pathology. Nevertheless, we observed that carbamazepine was useful in improving life quality in our patient, and should be considered as a first-line drug. To date, measles vaccination remains the only solution to SSPE.
    European Journal of Paediatric Neurology 02/2007; 11(1):43-5. DOI:10.1016/j.ejpn.2006.10.005 · 1.93 Impact Factor
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    ABSTRACT: Human leukocyte antigen (HLA) haplotypes (n = 187) were genotyped and assigned by the mode of inheritance in migrant families from North Africa who reside in the Paris, France, area. The distribution of alleles and haplotypes in that population was compared with the one obtained in a control population of ancient French natives residing in the same area (248 independent haplotypes also assigned by the mode of inheritance were studied). The results in migrants reveal the following: (1) a higher diversity in the distribution of HLA-A and -DRB1 alleles; (2) lower frequencies of alleles common in our region, such as A*0201 B*1501, B*4001, and DRB1*0401 and increased frequencies of minor subtypes, such as A*3002 and DRB1*0402; and (3) distinct distributions of B/Cw, DRB1/DQB1 or B/Cw/DRB1/DQB1 haplotypes. The results also revealed that the four most frequent five-allele haplotypes in controls i.e., HLA-A*0101/B*0801/Cw*0701/DRB1*0301/DQB1*0201; A*0301/B*0702/Cw*0702/DRB1*1501/DQB1*0602 (both of Indo-Celtic origin); A*2902/B*4403/Cw*1601/DRB1*0701/DQB1*0202 (frequent in Western-Europeans); and A*0201/B*1501/Cw*0304/DRB1*0401/DQB1*0302, represent 10.5% of the total haplotypes in controls but 1.6% in North Africans. Conversely, 9 five-allele haplotypes in multiple copy in North Africans (among which A*3002/B*1801/Cw*0501/DRB1*0301/DQB1*0201 of Paleo-North African origin and A*0201/B*0702/Cw*0702/DRB1*1501/DQB1*0602 of ancient European and Paleo-North African origin) represent 9.6% of the total haplotypes in North Africans but 2.4% in controls. These results thus suggest a low degree of admixture between the two populations.
    Human Immunology 08/2006; 67(7):540-50. DOI:10.1016/j.humimm.2005.10.017 · 2.28 Impact Factor
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    ABSTRACT: In this study we have identified frequent human leukocyte antigen (HLA)-A, -B, -C,-DRB1, and -DQB1 alleles, frequent HLA-B/C, HLA-DRB1/DQB1 two-allele associations, and the most common HLA-A/B/C/DRB1/DQB1 five-locus haplotypes in a population residing in the Paris, France, area. The study was carried out in 356 families of children awaiting hematopoietic stem-cell transplantation (HSCT), with the selection criterion that haplotypes could be assigned with certainty to both the patient and at least one parent. Parental haplotypes were HLA-A, -B serologically typed, and HLA-C, -DRB1, -DQB1 broadly typed by polymerase chain reaction-sequence-specific oligonucleotide probe. The alleles of the most frequent haplotypes were subsequently defined at a high-resolution level by polymerase chain reaction-sequence-specific primer. The results on the distribution of common alleles and common allele associations demonstrated similarities with the previously published data in Caucasian populations, as expected from the geographic origin of the studied population. More importantly, this study provides the largest listing of common B/C and DRB1/DQB1 associations and of common five-allele haplotypes defined with certainty in a Caucasian population to date. These results can be used to help estimate the likelihood of finding a suitable donor in unrelated HSCT and to delineate search strategies for potential donors.
    Human Immunology 07/2005; 66(6):721-31. DOI:10.1016/j.humimm.2005.02.007 · 2.28 Impact Factor