Publications by authors named "Annemarie van de Geer"

8 Publications

  • Page 1 of 1

Biomarkers to predict infection and infection-related complications during chemotherapy-induced neutropenia in acute myeloid leukaemia: a pilot study.

Br J Haematol 2021 Apr 8. Epub 2021 Apr 8.

Department of Blood Cell Research, Division Research and Landsteiner Laboratory of Amsterdam UMC, Sanquin Blood Supply, Amsterdam, the Netherlands.

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http://dx.doi.org/10.1111/bjh.17422DOI Listing
April 2021

Biomarkers for the Discrimination of Acute Kawasaki Disease From Infections in Childhood.

Front Pediatr 2020 22;8:355. Epub 2020 Jul 22.

Sanquin Research and Landsteiner Laboratory, Department of Blood Cell Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.

Kawasaki disease (KD) is a vasculitis of early childhood mimicking several infectious diseases. Differentiation between KD and infectious diseases is essential as KD's most important complication-the development of coronary artery aneurysms (CAA)-can be largely avoided by timely treatment with intravenous immunoglobulins (IVIG). Currently, KD diagnosis is only based on clinical criteria. The aim of this study was to evaluate whether routine C-reactive protein (CRP) and additional inflammatory parameters myeloid-related protein 8/14 (MRP8/14 or S100A8/9) and human neutrophil-derived elastase (HNE) could distinguish KD from infectious diseases. The cross-sectional study included KD patients and children with proven infections as well as febrile controls. Patients were recruited between July 2006 and December 2018 in Europe and USA. MRP8/14, CRP, and HNE were assessed for their discriminatory ability by multiple logistic regression analysis with backward selection and receiver operator characteristic (ROC) curves. In the discovery cohort, the combination of MRP8/14+CRP discriminated KD patients ( = 48) from patients with infection ( = 105), with area under the ROC curve (AUC) of 0.88. The HNE values did not improve discrimination. The first validation cohort confirmed the predictive value of MRP8/14+CRP to discriminate acute KD patients ( = 26) from those with infections ( = 150), with an AUC of 0.78. The second validation cohort of acute KD patients ( = 25) and febrile controls ( = 50) showed an AUC of 0.72, which improved to 0.84 when HNE was included. When used in combination, the plasma markers MRP8/14, CRP, and HNE may assist in the discrimination of KD from both proven and suspected infection.
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http://dx.doi.org/10.3389/fped.2020.00355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388698PMC
July 2020

MRP8/14 and neutrophil elastase for predicting treatment response and occurrence of flare in patients with juvenile idiopathic arthritis.

Rheumatology (Oxford) 2020 09;59(9):2392-2401

Department of Paediatric Immunology, Rheumatology and Infectious Disease, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam.

Objective: To study two neutrophil activation markers, myeloid-related protein (MRP) 8/14 and neutrophil elastase (NE), for their ability to predict treatment response and flare in patients with JIA.

Methods: Using samples from two cohorts (I and II), we determined MRP8/14 and NE levels of 32 (I) and 81 (II) patients with new-onset, DMARD-naïve arthritis and compared patients who responded to treatment (defined as fulfilling ≥ adjusted ACRpedi50 response and/or inactive disease) with non-responders (defined as fulfilling < adjusted ACRpedi50 response and/or active disease) at 6 and 12 months. Secondly, we compared biomarker levels of 54 (I) and 34 (II) patients with clinically inactive disease who did or did not suffer from a flare of arthritis after 6 or 12 months. Receiver operating characteristic analyses were carried out to study the predictive value of MRP8/14 and NE for treatment response and flare.

Results: For both cohorts, baseline MRP8/14 and NE levels for patients who did or did not respond to treatment were not different. Also, MRP8/14 and NE levels were not different in patients who did or did not flare. Receiver operating characteristic analysis of MRP8/14 and NE demonstrated areas under the curve <0.7 in both cohorts.

Conclusion: In our cohorts, MRP8/14 and NE could not predict treatment response. Also, when patients had inactive disease, neither marker could predict flares.
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http://dx.doi.org/10.1093/rheumatology/kez590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449815PMC
September 2020

Inherited p40phox deficiency differs from classic chronic granulomatous disease.

J Clin Invest 2018 08 6;128(9):3957-3975. Epub 2018 Aug 6.

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.

Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another. When overexpressed in NB4 neutrophil-like cells and EBV-transformed B cells in vitro, the mutant alleles were found to be LOF, with the exception of the p.R58C and c.120_134del alleles, which were hypomorphic. Particle-induced NADPH oxidase activity was severely impaired in the patients' neutrophils, whereas PMA-induced dihydrorhodamine-1,2,3 (DHR) oxidation, which is widely used as a diagnostic test for chronic granulomatous disease (CGD), was normal or mildly impaired in the patients. Moreover, the NADPH oxidase activity of EBV-transformed B cells was also severely impaired, whereas that of mononuclear phagocytes was normal. Finally, the killing of Candida albicans and Aspergillus fumigatus hyphae by neutrophils was conserved in these patients, unlike in patients with CGD. The patients suffer from hyperinflammation and peripheral infections, but they do not have any of the invasive bacterial or fungal infections seen in CGD. Inherited p40phox deficiency underlies a distinctive condition, resembling a mild, atypical form of CGD.
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http://dx.doi.org/10.1172/JCI97116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118590PMC
August 2018

Increased circulating interleukin-8 in patients with resistance to thyroid hormone receptor α.

Endocr Connect 2017 Nov;6(8):731-740

Department of Endocrinology and MetabolismAcademic Medical Center, Amsterdam, The Netherlands

Innate immune cells have recently been identified as novel thyroid hormone (TH) target cells in which intracellular TH levels appear to play an important functional role. The possible involvement of TH receptor alpha (TRα), which is the predominant TR in these cells, has not been studied to date. Studies in TRα mice suggest a role for this receptor in innate immune function. The aim of this study was to determine whether TRα affects the human innate immune response. We assessed circulating interleukin-8 concentrations in a cohort of 8 patients with resistance to TH due to a mutation of TRα (RTHα) and compared these results to healthy controls. In addition, we measured neutrophil and macrophage function in one of these RTHα patients (mutation D211G). Circulating interleukin-8 levels were elevated in 7 out of 8 RTHα patients compared to controls. These patients harbor different mutations, suggesting that this is a general feature of the syndrome of RTHα. Neutrophil spontaneous apoptosis, bacterial killing, NAPDH oxidase activity and chemotaxis were unaltered in cells derived from the RTHαD211G patient. RTHα macrophage phagocytosis and cytokine induction after LPS treatment were similar to results from control cells. The D211G mutation did not result in clinically relevant impairment of neutrophil or pro-inflammatory macrophage function. As elevated circulating IL-8 is also observed in hyperthyroidism, this observation could be due to the high-normal to high levels of circulating T found in patients with RTHα.
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http://dx.doi.org/10.1530/EC-17-0213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5670275PMC
November 2017

How neutrophils kill fungi.

Immunol Rev 2016 09;273(1):299-311

Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Neutrophils play a critical role in the prevention of invasive fungal infections. Whereas mouse studies have demonstrated the role of various neutrophil pathogen recognition receptors (PRRs), signal transduction pathways, and cytotoxicity in the murine antifungal immune response, much less is known about the killing of fungi by human neutrophils. Recently, novel primary immunodeficiencies have been identified in patients with a susceptibility to fungal infections. These human 'knock-out' neutrophils expand our knowledge to understand the role of PRRs and signaling in human fungal killing. From the studies with these patients it is becoming clear that neutrophils employ fundamentally distinct mechanisms to kill Candida albicans or Aspergillus fumigatus.
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http://dx.doi.org/10.1111/imr.12454DOI Listing
September 2016

Proinflammatory cytokine response toward fungi but not bacteria in chronic granulomatous disease.

J Allergy Clin Immunol 2016 09 5;138(3):928-930.e4. Epub 2016 May 5.

Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Pediatric Hematology, Immunology and Infectious Diseases, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

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http://dx.doi.org/10.1016/j.jaci.2016.03.035DOI Listing
September 2016

Impaired killing of Candida albicans by granulocytes mobilized for transfusion purposes: a role for granule components.

Haematologica 2016 05 22;101(5):587-96. Epub 2016 Jan 22.

Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Granulocyte transfusions are used to treat neutropenic patients with life-threatening bacterial or fungal infections that do not respond to anti-microbial drugs. Donor neutrophils that have been mobilized with granulocyte-colony stimulating factor (G-CSF) and dexamethasone are functional in terms of antibacterial activity, but less is known about their fungal killing capacity. We investigated the neutrophil-mediated cytotoxic response against C. albicans and A. fumigatus in detail. Whereas G-CSF/dexamethasone-mobilized neutrophils appeared less mature as compared to neutrophils from untreated controls, these cells exhibited normal ROS production by the NADPH oxidase system and an unaltered granule mobilization capacity upon stimulation. G-CSF/dexamethasone-mobilized neutrophils efficiently inhibited A. fumigatus germination and killed Aspergillus and Candida hyphae, but the killing of C. albicans yeasts was distinctly impaired. Following normal Candida phagocytosis, analysis by mass spectrometry of purified phagosomes after fusion with granules demonstrated that major constituents of the antimicrobial granule components, including major basic protein (MBP), were reduced. Purified MBP showed candidacidal activity, and neutrophil-like Crisp-Cas9 NB4-KO-MBP differentiated into phagocytes were impaired in Candida killing. Together, these findings indicate that G-CSF/dexamethasone-mobilized neutrophils for transfusion purposes have a selectively impaired capacity to kill Candida yeasts, as a consequence of an altered neutrophil granular content.
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http://dx.doi.org/10.3324/haematol.2015.136630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004374PMC
May 2016