Taco W Kuijpers

University of Amsterdam, Amsterdamo, North Holland, Netherlands

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Publications (224)1351.75 Total impact

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    ABSTRACT: Globally approximately 60 cases of C1q deficiency have been described with a high prevalence of Systemic Lupus Erythematosus (SLE). So far treatment has been guided by the clinical presentation rather than the underlying C1q deficiency. Recently, it was shown that C1q production can be restored by allogeneic hematopoietic stem cell transplantation. Current literature lacks information on disease progression and quality of life of C1q deficient persons which is of major importance to guide clinicians taking care of patients with this rare disease.
  • PLoS ONE 06/2015; 10(6):e0127178. DOI:10.1371/journal.pone.0127178 · 3.53 Impact Factor
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    ABSTRACT: Subtle structural and functional neuroretinal changes have been described in human immunodeficiency virus (HIV)-infected adults without retinitis treated with combination antiretroviral therapy (cART). However, studies on this subject in HIV-infected children are scarce. This study aimed to assess the presence of (neuro)retinal functional and structural differences between a group of perinatally HIV-infected children on cART and age-, sex-, ethnicity-, and socioeconomically matched healthy controls. All participants underwent an extensive ophthalmological examination, including functional tests as well as optical coherence tomography, to measure individual retinal layer thicknesses. Multivariable mixed linear regression models were used to assess possible associations between HIV status (and other HIV-related parameters) and ocular parameters, while accounting for the inclusion of both eyes and several known confounders. Thirty-three HIV-infected children (median age 13.7 years [interquartile range (IQR), 12.2-15.8], median CD4+ T-cell count 760 cells/mm3, 82% with an undetectable HIV viral load [VL]), and 36 controls (median age 12.1 years [IQR, 11.5-15.8]) were included. Contrast sensitivity (CS) was significantly lower in the HIV-infected group (1.74 vs. 1.76 logCS; P = 0.006). The patients had a significantly thinner foveal thickness (-11.2 μm, P = 0.012), which was associated with a higher peak HIV VL (-10.3 μm per log copy/mL, P = 0.016). In this study, we found a decrease in foveal thickness in HIV-infected children, which was associated with a higher peak VL. Longitudinal studies are warranted to confirm our findings and to determine the course and clinical consequences of these foveal changes.
    Investigative ophthalmology & visual science 06/2015; 56(6):3945-54. DOI:10.1167/iovs.15-16855 · 3.66 Impact Factor
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    ABSTRACT: To determine whether clinical, laboratory or Magnetic Resonance Imaging (MRI) measures differentiate Juvenile Idiopathic Arthritis (JIA) from other forms of active childhood arthritis. We prospectively collected data of 80 treatment-naïve patients clinically suspected of JIA with active non-infectious arthritis of (at least) one knee for <12 months duration. Upon presentation patients underwent clinical and laboratory assessments and contrast-enhanced MRI. MRI was not used as a diagnostic criterion. Forty-four (55 %) patients were clinically diagnosed with JIA, whereas in 36 (45 %) patients the diagnosis of JIA was discarded on clinical or laboratory findings. MRI-based synovitis was present in 27 (61.4 %) JIA patients and in 7 (19.4 %) non-JIA patients (P < 0.001). Five factors (male gender, physician's global assessment of overall disease activity, joints with limited range of motion, HLA-B27, MRI-based synovitis) were associated with the onset of JIA. In multivariate analysis MRI-based synovitis proved to be independently associated with JIA (OR 6.58, 95 % CI 2.36-18.33). In patients with MRI-based synovitis, the RR of having JIA was 3.16 (95 % CI 1.6-6.4). The presence of MRI-based synovitis is associated with the clinical onset of JIA. Physical examination could be supported by MRI, particularly to contribute in the early differentiation of different forms of non-infectious childhood arthritis. • Juvenile Idiopathic Arthritis (JIA) is a diagnosis of exclusion. • Differentiating JIA and other forms of childhood arthritis can be difficult. • MRI-techniques have substantially improved evaluation of joint abnormalities in JIA patients. • MRI-based synovitis is significantly associated with the clinical onset of JIA. • MRI could support physical examination in the early differentiation of childhood arthritis.
    European Radiology 05/2015; DOI:10.1007/s00330-015-3752-x · 4.34 Impact Factor
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    ABSTRACT: A 4-year-old Turkish girl of consanguineous parents was hospitalized for the evaluation of headaches and recurrent febrile episodes of unknown origin. Her medical history was unremarkable except for a few episodes of uncomplicated oral thrush. Meningitis was diagnosed and Candida albicans was the only pathogen identified by PCR and culture. Despite systemic antifungal multidrug therapy a prolonged course of 16 months of therapy was necessary to clear C. albicans from the cerebrospinal fluid (CSF). Molecular genetic analysis revealed a homozygous caspase recruitment domain 9 (CARD9) mutation (Q295X), which was reported to predispose to chronic mucocutaneous candidiasis. Immunologic workup excluded predisposing B- and T-cell defects. In addition, T cells producing IL-17 were repeatedly measured within the normal range. Analyses of neutrophils demonstrated normal NADPH oxidase activity in response to various stimuli including S. aureus and C. albicans. Additional neutrophilic functional testing, however, showed a decreased cytotoxicity to non-opsonized C. albicans, indicating an impaired killing mechanism against Candida spp. independent from the production of reactive oxygen species by the NADPH oxidase system. Since this defect was only demonstrated in the absence of opsonins, it might especially predispose to chronic C. albicans infections in the central nervous system (CNS) where opsonin concentrations are usually low. We therefore, that an additional neutrophil dependent defect CARD9 deficiency predisposes not only to chronic mucocutaneous candidiasis, but also to invasive chronic Candida infections, especially of the CNS.
    Plastic and Reconstructive Surgery 04/2015; DOI:10.1097/INF.0000000000000736 · 3.33 Impact Factor
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    ABSTRACT: Severe combined immune deficiency (SCID) is a fatal primary immunodeficiency usually presenting in the first months of life with (opportunistic) infections, diarrhea, and failure to thrive. Hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are curative treatment options. The objective of the study was to assess the morbidity, mortality, and diagnostic and therapeutic delay in children with SCID in the Netherlands in the last 15 years. These data may help to judge whether SCID should be considered to be included in our national neonatal screening program. In the period 1998-2013, 43 SCID patients were diagnosed in the Netherlands, 11 of whom were atypical SCID (presentation beyond the first year). The median interval between the first symptom and diagnosis was 2 months (range 0-1173 months). The total mortality was 42 %. In total, 32 patients were treated with HSCT of whom 8 were deceased. Nine patients died due to severe infectious complications before curative treatment could be initiated. Because of a high mortality of patients with SCID before HSCT could be initiated, only a national newborn screening program and pre-emptive HSCT or GT will be able to improve survival of these patients. "What is known" • SCID is a fatal disease if a curative hematopoietic stem cell transplantation cannot be performed in time. • Newborn screening for SCID enables early diagnosis in the asymptomatic phase. "What is new" • Nine out of 43 SCID patients in the Netherlands died due to severe infectious complications before curative treatment could be initiated. • Only newborn screening and pre-emptive curative therapy will improve survival of children with SCID in the Netherlands.
    European Journal of Pediatrics 04/2015; DOI:10.1007/s00431-015-2518-4 · 1.98 Impact Factor
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    ABSTRACT: Aicardi-Goutières syndrome (AGS) is a monogenic inflammatory encephalopathy caused by mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, or MDA5. Mutations in those genes affect normal RNA/DNA intracellular metabolism and detection, triggering an autoimmune response with an increase in cerebral IFN-α production by astrocytes. Microangiopathy and vascular disease also contribute to the neuropathology in AGS. In this study, we report that AGS gene silencing of TREX1, SAMHD1, RNASEH2A, and ADAR1 by short hairpin RNAs in human neural stem cell-derived astrocytes, human primary astrocytes, and brain-derived endothelial cells leads to an antiviral status of these cells compared with nontarget short hairpin RNA-treated cells. We observed a distinct activation of the IFN-stimulated gene signature with a substantial increase in the release of proinflammatory cytokines (IL-6) and chemokines (CXCL10 and CCL5). A differential impact of AGS gene silencing was noted; silencing TREX1 gave rise to the most dramatic in both cell types. Our findings fit well with the observation that patients carrying mutations in TREX1 experience an earlier onset and fatal outcome. We provide in the present study, to our knowledge for the first time, insight into how astrocytic and endothelial activation of antiviral status may differentially lead to cerebral pathology, suggesting a rational link between proinflammatory mediators and disease severity in AGS. Copyright © 2015 by The American Association of Immunologists, Inc.
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    ABSTRACT: The lectin pathway (LP) of complement has a protective function against invading pathogens. Recent studies have also shown that the LP plays an important role in ischemia/reperfusion (I/R)-injury. MBL-associated serine protease (MASP)-2 appears to be crucial in this process. The serpin C1-inhibitor is the major inhibitor of MASP-2. In addition, aprotinin, a Kunitz-type inhibitor, was shown to inhibit MASP-2 activity in vitro. In this study we investigated whether the Kunitz-type inhibitor tissue factor pathway inhibitor (TFPI) is also able to inhibit MASP-2. Ex vivo LP was induced and detected by C4-deposition on mannan-coated plates. The MASP-2 activity was measured in a fluid-phase chromogenic assay. rTFPI in the absence or presence of specific monoclonal antibodies was used to investigate which TFPI-domains contribute to MASP-2 inhibition. Here, we identify TFPI as a novel selective inhibitor of MASP-2, without affecting MASP-1 or the classical pathway proteases C1s and C1r. Kunitz-2 domain of TFPI is required for the inhibition of MASP-2. Considering the role of MASP-2 in complement-mediated I/R-injury, the inhibition of this protease by TFPI could be an interesting therapeutic approach to limit the tissue damage in conditions such as cerebral stroke, myocardial infarction or solid organ transplantation.This article is protected by copyright. All rights reserved
    European Journal of Immunology 02/2015; 45(2). DOI:10.1002/eji.201445070 · 4.52 Impact Factor
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    ABSTRACT: Mutations in DOCK8 result in autosomal recessive Hyper-IgE syndrome with combined immunodeficiency (CID). However, the natural course of disease, long-term prognosis, and optimal therapeutic management have not yet been clearly defined. In an international retrospective survey of patients with DOCK8 mutations, focused on clinical presentation and therapeutic measures, a total of 136 patients with a median follow-up of 11.3 years (1.3-47.7) spanning 1693 patient years, were enrolled. Eczema, recurrent respiratory tract infections, allergies, abscesses, viral infections and mucocutaneous candidiasis were the most frequent clinical manifestations. Overall survival probability in this cohort [censored for hematopoietic stem cell transplantation (HSCT)] was 87 % at 10, 47 % at 20, and 33 % at 30 years of age, respectively. Event free survival was 44, 18 and 4 % at the same time points if events were defined as death, life-threatening infections, malignancy or cerebral complications such as CNS vasculitis or stroke. Malignancy was diagnosed in 23/136 (17 %) patients (11 hematological and 9 epithelial cancers, 5 other malignancies) at a median age of 12 years. Eight of these patients died from cancer. Severe, life-threatening infections were observed in 79/136 (58 %); severe non-infectious cerebral events occurred in 14/136 (10 %). Therapeutic measures included antiviral and antibacterial prophylaxis, immunoglobulin replacement and HSCT. This study provides a comprehensive evaluation of the clinical phenotype of DOCK8 deficiency in the largest cohort reported so far and demonstrates the severity of the disease with relatively poor prognosis. Early HSCT should be strongly considered as a potential curative measure.
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    ABSTRACT: Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates.
    Frontiers in Immunology 01/2015; 6:11. DOI:10.3389/fimmu.2015.00011
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    ABSTRACT: Background: Despite the declined incidence of severe neurological complications such as HIV‐encephalopathy, HIV‐infection in children is still associated with a range of cognitive problems. Studies comparing HIV‐infected children to socioeconomically (SES)‐matched controls are lacking, while most HIV‐infected children in industrialized countries are immigrants with a relatively low SES. Methods: This cross‐sectional study included perinatally HIV‐infected children and controls matched for age, gender, ethnicity and SES, who completed a neuropsychological assessment (NPA) evaluating intelligence, information processing speed, attention, memory, executive‐ and visual‐motor functioning. Multivariate normative comparison (MNC) was used to assess the prevalence of cognitive impairment in the HIV‐infected group. Multivariable regression analyses were performed to identify HIV‐ and cART‐related factors associated with cognitive performance. Results: In total, 35 perinatally HIV‐infected (median age: 13.8 years, median CD4+ T‐cells: 770*106/L, 83% with an undetectable HIV VL) and 37 healthy children (median age: 12.1 years) were included. HIV‐infected children scored lower than the healthy controls on all cognitive domains (e.g. intelligence quotient (IQ): 76 [SD 15.7] and 87.5 [SD 13.6] for HIV‐infected versus healthy children; P=0.002). Cognitive impairment was found in 6 HIV‐infected children (17%). The CDC clinical category at HIV diagnosis was inversely associated with verbal IQ (CDC C: coefficient ‐22.98, P=0.010). Conclusion: Our results show that cognitive performance of HIV‐infected children is poor as compared to SES‐matched healthy controls. Gaining insight in these cognitive deficits is essential as subtle impairments may progress to more pronounced complications, that will influence future intellectual performance, job opportunities and community participation of HIV‐infected children.
    Clinical Infectious Diseases 12/2014; DOI:10.1093/cid/ciu1144 · 9.42 Impact Factor
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    ABSTRACT: The consumption of immunoglobulins (Ig) is increasing due to better recognition of antibody deficiencies, an aging population, and new indications. This review aims to examine the various dosing regimens and research developments in the established and in some of the relevant off-label indications in Europe. The background to the current regulatory settings in Europe is provided as a backdrop for the latest developments in primary and secondary immunodeficiencies and in immunomodulatory indications. In these heterogeneous areas, clinical trials encompassing different routes of administration, varying intervals, and infusion rates are paving the way toward more individualized therapy regimens. In primary antibody deficiencies, adjustments in dosing and intervals will depend on the clinical presentation, effective IgG trough levels and IgG metabolism. Ideally, individual pharmacokinetic profiles in conjunction with the clinical phenotype could lead to highly tailored treatment. In practice, incremental dosage increases are necessary to titrate the optimal dose for more severely ill patients. Higher intravenous doses in these patients also have beneficial immunomodulatory effects beyond mere IgG replacement. Better understanding of the pharmacokinetics of Ig therapy is leading to a move away from simplistic "per kg" dosing. Defective antibody production is common in many secondary immunodeficiencies irrespective of whether the causative factor was lymphoid malignancies (established indications), certain autoimmune disorders, immunosuppressive agents, or biologics. This antibody failure, as shown by test immunization, may be amenable to treatment with replacement Ig therapy. In certain immunomodulatory settings [e.g., idiopathic thrombocytopenic purpura (ITP)], selection of patients for Ig therapy may be enhanced by relevant biomarkers in order to exclude non-responders and thus obtain higher response rates. In this review, the developments in dosing of therapeutic immunoglobulins have been limited to high and some medium priority indications such as ITP, Kawasaki' disease, Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, myasthenia gravis, multifocal motor neuropathy, fetal alloimmune thrombocytopenia, fetal hemolytic anemia, and dermatological diseases.
    Frontiers in Immunology 12/2014; 5:629. DOI:10.3389/fimmu.2014.00629
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    ABSTRACT: REVIEW ARTICLE published: 12December2014 doi: 10.3389/fimmu.2014.00629 Isdosingoftherapeuticimmunoglobulinsoptimal?Areviewofathree-decadelongdebateinEurope JacquelineKerr 1, IsabellaQuinti 2, MarthaEibl 3, HelenChapel 4, PeterJ.Späth5,W.A.CarrockSewell 6, AbdulgabarSalama7, IvoN.vanSchaik 8,TacoW.Kuijpers9 and Hans-HartmutPeter 10* 1 Section Poly-andMonoclonalAntibodies,PaulEhrlichInstitut,Langen,Germany 2 Department ofMolecularMedicine,SapienzaUniversityofRome,Rome,Italy 3 ImmunologischeTagesklinik,Vienna,Austria 4 NuffieldDepartmentofMedicine,UniversityofOxford,Oxford,UK 5 InstituteofPharmacology,UniversityofBern,Bern,Switzerland 6 Hull YorkMedicalSchool,UniversityofLincoln,Lincoln,UK 7 ZentrumfürTransfusionsmedizinu.Zelltherapie,Charité,Berlin,Germany 8 Department ofNeurology,AcademicMedicalCenter(AMC),UniversityofAmsterdam,Amsterdam,Netherlands 9 Department ofPediatricHematology,ImmunologyandInfectiousdisease,AcademicMedicalCenter(AMC),UniversityofAmsterdam,Amsterdam,Netherlands 10 CentrumfürchronischeImmunodeficienz(CCI),UniversityMedicalCentre,UniversityofFreiburg,FreiburgimBreisgau,Germany Editedby: Albert Farrugia,UniversityofWestern Australia,Australia Reviewedby: Antonio Condino-Neto,Universityof São Paulo,Brazil Alessandro Plebani,Universityof Brescia, Italy *Correspondence: Hans-Hartmut Peter,Centrumfür chronischeImmundefizienz(CCI), Engesserstr.4,D-79108Freiburgim Breisgau, Germany e-mail: hans-hartmut.peter@ uniklinik-freiburg.de Theconsumptionofimmunoglobulins(Ig)isincreasingduetobetterrecognitionofantibodydeficiencies,anagingpopulation,andnewindications.Thisreviewaimstoexaminethevariousdosingregimensandresearchdevelopmentsintheestablishedandinsomeoftherelevantoff-labelindicationsinEurope.ThebackgroundtothecurrentregulatorysettingsinEuropeisprovidedasabackdropforthelatestdevelopmentsinprimaryandsecondaryimmunodefiienciesandinimmunomodulatoryindications.Intheseheterogeneousareas,clinicaltrialsencompassingdifferentroutesofadministration,varyingintervals,andinfusionratesarepavingthewaytowardmoreindividualizedtherapyregimens.Inprimaryantibodydeficiencies,adjustmentsindosingandintervalswilldependontheclinicalpresentation,effectiveIgGtroughlevelsandIgGmetabolism.Ideally,individualpharmacokineticpro-filesinconjunctionwiththeclinicalphenotypecouldleadtohighlytailoredtreatment.Inpractice,incrementaldosageincreasesarenecessarytotitratetheoptimaldoseformoreseverelyillpatients.Higherintravenousdosesinthesepatientsalsohavebenefi-cialimmunomodulatoryeffectsbeyondmereIgGreplacement.BetterunderstandingofthepharmacokineticsofIgtherapyisleadingtoamoveawayfromsimplistic“perkg”dosing.Defectiveantibodyproductioniscommoninmanysecondaryimmunodeficien-ciesirrespectiveofwhetherthecausativefactorwaslymphoidmalignancies(establishedindications),certainautoimmunedisorders,immunosuppressiveagents,orbiologics.Thisantibodyfailure,asshownbytestimmunization,maybeamenabletotreatmentwithreplacementIgtherapy.Incertainimmunomodulatorysettings[e.g.,idiopathicthrombo-cytopenicpurpura(ITP)],selectionofpatientsforIgtherapymaybeenhancedbyrelevantbiomarkersinordertoexcludenon-respondersandthusobtainhigherresponserates.Inthisreview,thedevelopmentsindosingoftherapeuticimmunoglobulinshavebeenlimitedtohighandsomemediumpriorityindicationssuchasITP,Kawasaki’disease,Guillain–Barrésyndrome,chronicinflammatorydemyelinatingpolyradiculoneuropathy,myastheniagravis,multifocalmotorneuropathy,fetalalloimmunethrombocytopenia,fetalhemolyticanemia,anddermatologicaldiseases. Keywords:IVIG,SCIG,replacementtherapy,immunomodulation,dosing INTRODUCTION Indicationsforintravenous(IVIG)andsubcutaneous(SCIG) immunoglobulin(Ig)therapiesaresteadilyincreasingandthe annualdemandhastripledinthelast15yearsreachingaworld- wideconsumptionof~130metrictonsin2012(1). Shortagesin supplyhaveoccurredinthepastandcostpressureonhealthsys- temsworldwideisgrowingTheincreaseddemandfortherapeutic Ighasbeenmetbyincreasingthenumberofplasmadonorsand byintroducingnewhigh-yieldfractionationprocedures,which in somecaseshavebeenaccompaniedbyincreasesinratesof hemolyticanemia. ReportsinvolvingalternativedosesgiveninbothIgreplace- mentandimmunomodulatoryindicationsarequestioningcur- rentpractice.These,togetherwithemergingbiomarkersassociated withIg-responderandnon-responderstatus,inviteclosescrutiny ofindicationsfor,andmethodsofadministering,IVIGandSCIG use inthefuture.TraditionaldosingofIghasreliedheavily ona“perkgofbodyweight”calculation,whichhasnowbeen www.frontiersin.org December 2014|Volume5|Article629| 1
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    ABSTRACT: BACKGROUND:: Immigrant HIV-infected adults in industrialized countries show a poorer clinical and virological outcome compared to native patients. We aimed to investigate potential differences in clinical, immunological and virological outcome in Dutch HIV-infected children born in the Netherlands (NL) versus born in Sub-Saharan Africa (SSA) in a national cohort-analysis. METHODS:: We included all HIV-infected children registered between 1996 and 2013. Descriptive statistics, mixed-effects models and Cox proportional hazard models were used to investigate differences between groups. RESULTS:: In total, 319 HIV-infected children were registered. The majority of these children were born in SSA (n=148, 47%) or NL (n=113, 36%) and most were black (n=158, 61%). Children born in NL were diagnosed at a median age of 1.2 years and initiated combination antiretroviral therapy (cART) at a median age of 2.6 years, compared to 3.7 and 5.3 years respectively for children born in SSA (HIV-diagnosis: P<0.001; cART initiation: P<0.001). Despite a lower initial CD4 T-cell Z-score in children born in SSA, their immunological reconstitution was similar to children from NL. Virological suppression was achieved in the majority of all cART-treated children (NL:96%, SSA:94%). There was no difference in the occurrence or timing of virological failure. CONCLUSIONS:: The majority of immigrant HIV-infected children living in NL were born in SSA. Children born in SSA were diagnosed and initiated cART at an older age than children born in NL. Despite initial differences in CD4 T-cell counts and HIV viral load, the long-term immunological and virological response to cART was similar in both groups.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 11/2014; Nov(2). DOI:10.1097/QAI.0000000000000431 · 4.39 Impact Factor
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    ABSTRACT: Group B streptococcus is the most common cause of neonatal infections. We studied the clinical and molecular epidemiology of invasive group B streptococcus infection in children younger than 3 months in the Netherlands over 25 years. We assessed the effect of the Dutch guidelines, introduced in 1999, for prevention of group B streptococcus, consisting of intravenous antibiotic prophylaxis during labour in cases of premature labour, prolonged rupture of membranes, or fever during delivery. We did this nationwide surveillance study with data from 1987 to 2011, from the Netherlands Reference Laboratory for Bacterial Meningitis. We included data for patients aged 3 months or younger with positive blood culture or cerebrospinal fluid culture for group B streptococcus and Escherichia coli infection. Early onset was defined as less than 7 days after birth and late onset was defined as 7 or more days after birth. We did multilocus sequence typing of a random subset of group B streptococcus samples to assess changes in sequence type (Mann-Kendall trend test) and the distribution of clonal complexes (χ(2) and Fisher exact test) before the introduction of prevention guidelines (1987-99) and afterwards (2000-11). We compared incidences and the distribution of clonal complexes before and after the introduction of guidelines. Most cases of group B streptococcus had early onset (696/1075; 65%). The incidence of invasive group B streptococcus infection increased from 0·20 per 1000 livebirths in 1987, to 0·32 per 1000 livebirths in 2011 (p<0·0001). The incidence of early-onset disease increased from 0·11 per 1000 livebirths to 0·19 per 1000 livebirths (p<0·0001). The incidence of invasive Escherichia coli infection was 0·05 in 1987, and 0·16 in 2011 (p=0·17). Early-onset group B streptococcus infection caused by isolates belonging to clonal complex 17 was more common in the post-implementation period than in the pre-implementation period (p=0·002). The introduction of prevention guidelines for invasive group B streptococcus disease in 1999 did not reduce the incidence of disease in neonates. The guidelines should be reassessed and alternative approaches to prevent infant invasive group B streptococcus disease should be sought. National Institute of Public Health and the Environment, the European Union's seventh framework programme, Netherlands Organization for Health Research and Development, Academic Medical Center, and the European Research Council. Copyright © 2014 Elsevier Ltd. All rights reserved.
    The Lancet Infectious Diseases 11/2014; 14(11):1083-9. DOI:10.1016/S1473-3099(14)70919-3 · 19.45 Impact Factor
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    ABSTRACT: In immune thrombocytopenia (ITP) and warm autoimmune hemolytic anemia (wAIHA), circulating IgG-opsonized blood cells are cleared from the circulation by macrophages. Administration of intravenous immunoglobulin (IVIg) can prevent uptake, but the exact working mechanism is not known. The prevailing theory from murine studies, which states that Fc-sialylated IgG alters the balance between activating and inhibitory Fc-gamma receptors (FcγRs) by inducing upregulation of the inhibitory FcγRIIb on effector macrophages, is currently debated. We studied phagocytosis of IgG-opsonized blood cells in a human system, assessing the effect of IVIg and blocking anti-FcγR F(ab')2 fragments on uptake by monocyte-derived macrophages (both M1 and M2 macrophages). Phagocytosis was remarkably sensitive to administration of IVIg but unexpectedly, recombinant Fc-sialylated IgG or sialic acid-enriched IVIg were equally active as unsialylated IgG fractions in mediating this inhibition - independent of FcγRIIb expression. Instead, IVIg inhibited phagocytosis by direct blockade of FcγRs. IgG fractions enriched for IgG-dimers with enhanced avidity for FcγRs showed increased inhibition compared to monomeric IgG fractions. Together, our data demonstrate that inhibition of IgG-mediated phagocytosis in human macrophages by IVIg is dependent on the capacity to directly bind FcγRs but independent of FcγRIIb or sialylation of the Fc fragment in the human setting.
    Blood 10/2014; 124(25). DOI:10.1182/blood-2014-05-576835 · 10.43 Impact Factor
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    ABSTRACT: Absolute numbers of lymphocytes are decreased in uninfected infants born to HIV-1-infected women (HIV-1-exposed). Although the exact mechanism is unknown, fetal exposure to maternal HIV-1-infection could prime the immune system and affect T cell trafficking. We compared the expression of chemokine receptors on cord blood CD4(+) T cells from HIV-1-exposed children and healthy controls. At baseline CD4(+) T cells had a largely naïve phenotype. However, stimulation with cytokines resulted in an upregulation of inflammatory response-related chemokine receptors on CD4(+) T cells, with HIV-1-exposed infants having a significantly higher frequency of CD4(+) T cells expressing, in particularly Th2 associated chemokine receptors (CCR3 p < 0.01, CCR8 p = 0.03). Numbers of naive CCR7(+) CD4(+) T cells were reduced (p = 0.01) in HIV-1-exposed infants. We further assessed whether the inflammatory phenotype was associated with susceptibility to HIV-1 and detected higher levels of p24 upon in in vitro infection of stimulated CD4(+) T cells of HIV-1-exposed infants. In summary, fetal exposure to HIV-1 primes the immune system in the infant leading to an enhanced immune activation and altered T cell homing, with potential ramifications regarding T cell responses and the acquisition of HIV-1 as an infant.
    Scientific Reports 10/2014; 4:6690. DOI:10.1038/srep06690 · 5.58 Impact Factor
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    ABSTRACT: Uptake of oxLDL and foam cell formation by macrophages is one of the first steps in the development of atherosclerosis. Recently, PKCδ has been implicated as a regulator of oxLDL uptake and foam cell formation via down-regulation of PKCβ and scavenger receptors CD36 and SR-A expression. Here we describe studies in which we have re-evaluated the role of PKCδ in oxLDL uptake and foam cell formation.
    Cardiovascular Research 09/2014; DOI:10.1093/cvr/cvu213 · 5.81 Impact Factor
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    ABSTRACT: To assess the sequence and type of active joints in a cohort of newly diagnosed juvenile idiopathic arthritis (JIA) patients with full access to current treatment at first visit and during a follow-up period of 5-years, in order to identify an index joint/group of joints for magnetic resonance imaging in JIA. Patient charts of all consecutive newly diagnosed JIA patients with a follow-up duration of at least 5 years were analyzed. Patients were derived from two tertiary pediatric rheumatology centers. Patient characteristics and data concerning the presence of joints with arthritis and the use of medication were recorded. Findings from 95 JIA patients [39 (41 %) oligoarticular and 56 (59 %) polyarticular] were analyzed. At first visit, distribution of active joints among patients was as follows: knee (n = 70, 74 %), ankle (n = 55, 58 %), elbow (n = 23, 24 %), wrist (n = 23, 24 %), metacarpophalangeal (MCP) (n = 20, 21 %), proximal interphalangeal (PIP) (n = 13, 14 %), hip (n = 6, 6 %), shoulder (n = 5, 5 %), and distal interphalangeal (DIP) (n = 4, 4 %) joints. After a follow-up period of 5 years, the cumulative percentage of patients with specific joint involvement changed into: knee (n = 88, 93 %), ankle (n = 79, 83 %), elbow (n = 43, 45 %), wrist (n = 38, 40 %), MCP (n = 36, 38 %), PIP (n = 29, 31 %), shoulder (n = 20, 21 %), hip (n = 17, 19 %), and DIP (n = 9, 10 %) joints. Despite changes in treatment strategies over the years, the knee remains the most commonly involved joint at onset and during follow-up in JIA, followed by the ankle, elbow, and wrist. For the evaluation of outcome with MRI, the knee appears the most appropriate joint in JIA.
    Rheumatology International 08/2014; DOI:10.1007/s00296-014-3108-x · 1.63 Impact Factor
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    ABSTRACT: Background A chronic illness, such as Juvenile Idiopathic Arthritis (JIA), has an impact on the whole family, especially on parents caring for the ill child. Therefore the aim of this study is to evaluate parental Health Related Quality of Life (HRQOL) and parental perceptions of child vulnerability (PPCV) and associated variables in parents of a child with JIA. Methods Parents of all JIA patients (0–18 years) in Amsterdam, the Netherlands, were eligible. HRQOL was measured using the TNO-AZL Questionnaire (TAAQOL) and PPCV using the Child Vulnerability Scale (CVS). The HRQOL of parents of a child with JIA was compared to a norm population, and differences between parents of a child with JIA and active arthritis versus parents of a child with JIA without active arthritis were analyzed (ANOVA). For PPCV, parents of a child with JIA were compared to a norm population, including healthy and chronically ill children (Chi2, Mann-Whitney U test). Variables associated with PPCV were identified by logistic regression analyses. Results 155 parents (87.5% mothers) completed online questionnaires. JIA parents showed worse HRQOL than parents of healthy children on one out of twelve domains: fine motor HRQOL (p < .001). Parents of children with active arthritis showed worse HRQOL regarding daily activities (p < .05), cognitive functioning (p < .01) and depressive emotions (p < .05) compared to parents of children without active arthritis. Parents of children with JIA perceived their child as more vulnerable than parents of a healthy child (p < .001) and parents of a chronically ill child (p < .001). Parents of children with active arthritis reported higher levels of PPCV (p < .05) than parents of children without active arthritis. A higher degree of functional disability (p < .01) and shorter disease duration (p < .05) were associated with higher levels of PPCV. Conclusion The HRQOL of JIA parents was comparable to the HRQOL of parents of a healthy child. JIA parents of a child with active arthritis showed worse HRQOL than parents of a child without active arthritis. Parents perceived their child with JIA as vulnerable.
    Pediatric Rheumatology 08/2014; 12:34. DOI:10.1186/1546-0096-12-34 · 1.62 Impact Factor

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  • 1991–2015
    • University of Amsterdam
      • • Faculty of Medicine AMC
      • • Department of Paediatrics
      • • Central Laboratory of the Netherlands Red Cross Blood Transfusion Service
      Amsterdamo, North Holland, Netherlands
  • 2003–2014
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 2001–2014
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Academic Medical Center
      • • Department of Paediatrics
      Amsterdamo, North Holland, Netherlands
  • 2006–2013
    • VU University Amsterdam
      • Department of Clinical Chemistry
      Amsterdamo, North Holland, Netherlands
  • 2012
    • University of Freiburg
      • Faculty of Biology
      Freiburg, Baden-Württemberg, Germany
  • 2010–2011
    • Genome Institute of Singapore
      Tumasik, Singapore
    • Sanquin Blood Supply Foundation
      • Phagocyte Laboratory
      Amsterdamo, North Holland, Netherlands
  • 1991–2006
    • Hong Kong Red Cross Blood Transfusion Service
      Hong Kong, Hong Kong