Antoine van Kampen

Antoine van Kampen
Academisch Medisch Centrum Universiteit van Amsterdam | AMC · Department of Clinical Epidemiology and Biostatistics

Prof. dr.

About

260
Publications
24,311
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5,450
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Additional affiliations
January 2006 - December 2011
January 2002 - December 2012
University of Amsterdam

Publications

Publications (260)
Article
Full-text available
Delineating the origins and properties of antibodies elicited by SARS-CoV-2 infection and vaccination is critical for understanding their benefits and potential shortcomings. Therefore, we investigate the SARS-CoV-2 spike (S)-reactive B cell repertoire in unexposed individuals by flow cytometry and single-cell sequencing. We show that ∼82% of SARS-...
Article
Full-text available
A major goal of current HIV-1 vaccine design efforts is to induce broadly neutralizing antibodies (bNAbs). The VH1-2-derived bNAb IOMA directed to the CD4-binding site of the HIV-1 envelope glycoprotein is of interest because, unlike the better-known VH1-2-derived VRC01-class bNAbs, it does not require a rare short light chain complementarity-deter...
Article
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Background In patients with rheumatoid arthritis (RA) different joints were shown to share the same dominant T-cell clones, suggesting shared characteristics of the inflammatory process and indicating that strategies to selectively target the antigen receptor might be feasible. Since T- and B-lymphocytes closely interact in adaptive responses, we a...
Preprint
Sequencing of B cell and T cell immune receptor repertoires helps us to understand the adaptive immune response, although it only provides information about the clonotypes and their frequencies. Generally, additional time-consuming or expensive experiments are required to further characterize the identified (dominant) clones by measuring, for examp...
Article
A significant proportion of multiple sclerosis (MS) patients treated with interferon beta-1a (Rebif™) develop anti-drug antibodies (ADA) with a negative impact on treatment efficacy. We hypothesized that high-throughput B-cell receptor (BCR) repertoire analysis could be used to predict and monitor ADA development. To study this we analyzed 228 peri...
Article
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Affinity maturation is an evolutionary process by which the affinity of antibodies (Abs) against specific antigens (Ags) increases through rounds of B-cell proliferation, somatic hypermutation, and positive selection in germinal centres (GC). The positive selection of B cells depends on affinity, but the underlying mechanisms of affinity discrimina...
Article
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Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin’s lymphoma. It is a germinal center (GC)–derived, aggressive, and heterogeneous disease. Several transcription factors and signaling pathways that play a central role in the progression of the GC reaction and B-cell differentiation have been shown to play an oncogenic role in d...
Article
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Retinal degeneration is a common feature in peroxisomal disorders leading to blindness. Peroxisomes are present in the different cell types of the retina; however, their precise contribution to retinal integrity is still unclear. We previously showed that mice lacking the central peroxisomal β-oxidation enzyme, multifunctional protein 2 (MFP2), dev...
Article
Full-text available
Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, affecting approximately 1% of the general population. To alleviate symptoms and ameliorate joint damage, chronic use of immunosuppressives is needed. However, these treatments are only partially effective and may lead to unwanted side effects. Therefore,...
Article
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Memory B cells and antibody-secreting plasma cells are generated within germinal centers during affinity maturation in which B-cell proliferation, selection, differentiation, and self-renewal play important roles. The mechanisms behind memory B cell and plasma cell differentiation in germinal centers are not well understood. However, it has been su...
Article
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Circadian misalignment, as seen in shift work, is associated with an increased risk to develop type 2 diabetes. In an experimental setting, we recently showed that a rapid day-night shift for 3 consecutive nights leads to misalignment of the core molecular clock, induction of the PPAR pathway, and insulin resistance in skeletal muscle of young, hea...
Article
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Comprehensive metabolomic and lipidomic mass spectrometry methods are in increasing demand; for instance, in research related to nutrition and aging. The nematode Caenorhabditis elegans is a key model organism in these fields, owing to the large repository of available C. elegans mutants and their convenient natural lifespan. Here, we describe a ro...
Article
Full-text available
High-throughput T-cell receptor repertoire sequencing constitutes a powerful tool to study T cell responses at the clonal level. However, it does not give information on the functional phenotype of the responding clones and lacks a statistical framework for quantitative evaluation. To overcome this, we combined datasets from different experiments,...
Article
Full-text available
Patients lacking multifunctional protein 2 (MFP2), the central enzyme of the peroxisomal β-oxidation pathway, develop retinopathy. This pathway is involved in the metabolism of very long chain (VLCFAs) and polyunsaturated (PUFAs) fatty acids, which are enriched in the photoreceptor outer segments (POS). The molecular mechanisms underlying the retin...
Article
Full-text available
Germinal centers play a key role in the adaptive immune system since they are able to produce memory B cells and plasma cells that produce high affinity antibodies for an effective immune protection. The mechanisms underlying cell-fate decisions are not well understood but asymmetric division of antigen, B-cell receptor affinity, interactions betwe...
Article
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ACBD5 deficiency is a novel peroxisome disorder with a largely uncharacterized pathology. ACBD5 was recently identified in a tethering complex mediating membrane contacts between peroxisomes and the endoplasmic reticulum (ER). An ACBD5-deficient mouse was analyzed to correlate ACBD5 tethering functions with the disease phenotype. ACBD5-deficient mi...
Article
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Abstract: Breast cancer is one of the leading causes of death for women worldwide. Patients whose tumors express Estrogen Receptor α account for around 70% of cases and are mostly treated with targeted endocrine therapy. However, depending on the degree of severity of the disease at diagnosis, 10 to 40% of these tumors eventually relapse due to res...
Article
Full-text available
Background: Estrogen receptor (ER) positive breast cancer is often effectively treated with drugs that inhibit ER signaling, i.e., tamoxifen (TAM) and aromatase inhibitors (AIs). However, 30% of ER+ breast cancer patients develop resistance to therapy leading to tumour recurrence. Changes in the methylation profile have been implicated as one of t...
Preprint
Full-text available
Comprehensive metabolomic and lipidomic mass spectrometry methods are in increasing demand, for instance in research related to nutrition and aging. The nematode C. elegans is a key model organism in these fields, due to the large repository of available C. elegans mutants and their convenient natural lifespan. Here, we describe a robust and sensit...
Preprint
Full-text available
Breast cancer is one of the leading causes of death for women worldwide. Patients whose tumors express Estrogen Receptor α (ERα) account for around 70% of cases and are mostly treated with targeted endocrine therapy. However, 40% of these tumors eventually relapse due to resistance development and further treatment of these patients is highly ineff...
Article
Full-text available
Sjögren‐Larsson syndrome (SLS) is a rare neurometabolic syndrome caused by deficient fatty aldehyde dehydrogenase. Patients exhibit intellectual disability, spastic paraplegia and ichthyosis. The accumulation of fatty alcohols and fatty aldehydes has been demonstrated in plasma and skin but never in brain. Brain magnetic resonance imaging and spect...
Article
Full-text available
X-linked adrenoleukodystrophy (ALD) is a peroxisomal metabolic disorder with a highly complex clinical presentation. ALD is caused by mutations in the ABCD1 gene, and is characterized by the accumulation of very long-chain fatty acids in plasma and tissues. Disease-causing mutations are ‘loss of function’ mutations, with no prognostic value with re...
Preprint
Full-text available
X-linked adrenoleukodystrophy (ALD) is a peroxisomal metabolic disorder with a highly complex clinical presentation. ALD is caused by mutations in the ABCD1 gene, and is characterized by the accumulation of very long-chain fatty acids in plasma and tissues. Disease-causing mutations are ′loss of function′ mutations, with no prognostic value with re...
Preprint
Full-text available
Background: Estrogen receptor (ER) positive breast cancer is often effectively treated with drugs that inhibit ER signaling, i.e., tamoxifen (TAM) and aromatase inhibitors (AIs). However, 30% of ER+ breast cancer patients develop resistance to therapy leading to tumour recurrence. Changes in the methylation profile have been implicated as one of th...
Article
Slowing down translation in either the cytosol or the mitochondria is a conserved longevity mechanism. Here, we found a non-interventional natural correlation of mitochondrial and cytosolic ribosomal proteins (RPs) in mouse population genetics, suggesting a translational balance. Inhibiting mitochondrial translation in C. elegans through mrps-5 RNA...
Preprint
Full-text available
Background: Estrogen receptor (ER) positive breast cancer is often effectively treated with drugs that inhibit ER signaling, i.e., tamoxifen (TAM) and aromatase inhibitors (AIs). However, about 30% of ER+ breast cancer patients develop resistance to therapy leading to tumour recurrence. Changes in the methylation profile have been implicated as one...
Article
Full-text available
CTP:phosphoethanolamine cytidylyltransferase (ET), encoded by PCYT2, is the rate-limiting enzyme for phosphatidylethanolamine synthesis via the CDP-ethanolamine pathway. Phosphatidylethanolamine is one of the most abundant membrane lipids and is particularly enriched in the brain. We identified five individuals with biallelic PCYT2 variants clinica...
Article
Full-text available
Many autoimmune diseases are hallmarked by autoreactive B and plasma cell responses that are directly or indirectly involved in disease pathogenesis. These B-cell responses show large variability between diseases, both in terms of the secreted autoantibody repertoire and the dynamics and characteristics of the underlying B-cell responses. Hence, di...
Article
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Objective To gain more insight into the dynamics of lymphocyte depletion and develop new predictors of clinical response to rituximab in rheumatoid arthritis (RA). Methods RNA-based next-generation sequencing was used to analyse the B cell receptor (BCR) repertoire in peripheral blood and synovial tissue samples collected from 24 seropositive pati...
Article
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Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association sign...
Article
Preoperative biliary drainage (PBD) is used routinely in the evaluation of patients with potentially resectable perihilar cholangiocarcinoma to relieve cholestasis and improve the liver's resilience to surgery. Little preclinical or translatational data are, however, currently available to guide the use of PBD in this patient group. The effect of P...
Article
Genetic and immunological evidence clearly points to a role for T cells in the pathogenesis of rheumatoid arthritis (RA). Selective targeting of such disease-associated T cell clones might be highly effective while having few side effects. However, such selective targeting may only be feasible if the same T cell clones dominate the immune response...
Conference Paper
Background Rituximab (RTX) induces more than 98% depletion of the CD20 +B cells in blood after a single injection, yet 35% to 50% of RA treated patients show a poor response to the therapy¹. Despite the identification of many different biomarkers, mostly in the B cell compartment², adequate prediction of response to RTX treatment is still quite cha...
Conference Paper
Full-text available
Background Sjögren’s syndrome (SS) is the autoimmune disease with the highest risk of lymphoma development. SS patients develop most frequently MALT lymphoma and to a lesser extent diffuse large B-cell lymphoma (DLBCL). Previously, we have shown that at least 40% of salivary gland MALT lymphomas express groups of near identical (also called stereot...
Conference Paper
Background A phase characterised by the presence of specific autoantibodies and arthralgia’s in the absence of clinically evident synovial inflammation often precedes the onset of rheumatoid arthritis (RA). However, only a subset of these RA-risk individuals will develop active disease in the short term¹. Recent findings show that dominant B-cell r...
Article
Full-text available
Peroxisomes are ubiquitous cell organelles that play an important role in lipid metabolism. Accordingly, peroxisomal disorders, including the peroxisome biogenesis disorders and peroxisomal single-enzyme deficiencies, are associated with aberrant lipid metabolism. Lipidomics is an emerging tool for diagnosis, disease-monitoring, identifying lipid b...
Article
Full-text available
Purpose To identify the protein profiles in vitreous associated with retinal fibrosis, angiogenesis, and neurite formation in epiretinal fibrovascular membranes (FVMs) in patients with proliferative diabetic retinopathy (PDR). Methods Vitreous samples of 5 non-diabetic control patients with vitreous debris and 7 patients with PDR membranes were sc...
Article
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Use of some HIV-1 nucleoside reverse transcriptase inhibitors (NRTI) is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitochondrial dysfunction after chronic exposure to specific NRTIs has predominantly been assigned to mitochondrial polymerase-γ inhibition by NRTIs. Howeve...
Data
Protein concentrations in vitreous of control and PDR patients in independent study group. Protein concentrations were determined by Quantibody arrays in patients with macular hole (CON) and patients with proliferative diabetic retinopathy (PDR) that underwent vitreoretinal surgery. (PDF)
Data
Significantly modulated human vitreous proteins. Proteins in vitreous detected by the RayBio® L‐Series 507 Biotin Label‐based Antibody Array that were significantly modulated in a subset of PDR patients (n = 7) relative to non‐diabetic controls (n = 5). (PDF)
Data
Ang2 protein is increased in vitreous of PDR patients with FVMs. In an independent study group protein levels of Ang2, as detected by Quantibody arrays, were log10 transformed to obtain a normal distribution. Differences between groups were analyzed by a Student's t-test. CON, non-diabetic control patients; PDR–FVM, PDR patients without FVMs; PDR +...
Data
NRTIs pre-exposure protected against subsequent paraquat exposure. 4mM paraquat (PQ) survival assay of NRTI exposed animals. Statistics were calculated by two sided student’s t-test assuming unequal variance, compared to the control of that same time point (72h of PQ exposure). (TIF)
Data
Supplementation of NAC does not affect movement. The number of sigmoidal body bends per worm per minute can be used as a proxy for fitness. Anti-oxidant concentration = 100μM. Statistics were calculated by two sided student’s t-test assuming unequal variance compared to control of that same time point. n.s. = not significant. (DOCX)
Data
Primer details. Gene nomenclature, Gen bank accession code, primer sequences, and size and predicted Tm of the amplified products. (PDF)
Data
H2O2 and paraquat do not influence OCR. Immediate OCR rates after injection of H2O2 and paraquat (PQ) do not change. The lack of these pro-oxidants to have an immediate effect on OCR supports the observations that they do not directly inhibit MRC complex function at the concentrations used in this study [53,54]. (TIF)
Data
NAC does not alter ATP levels. ATP levels did not change upon exposure to 500μM NAC. In vivo ATP levels measured after 2 minutes of exposure. (TIF)
Data
AZT portrays a biphasic dose response in C. elegans. In accordance with mitohormetic events triggered by inhibited MRC function and an increase in ROS, 200μM AZT caused significant lifespan extension in C. elegans. An increase in AZT concentration above 200μM steadily decreased life span in L4 animals, indicating that NRTIs cause a biphasic dose re...
Data
NRTIs likely did not cause lifespan extension through caloric restriction. In C. elegans, caloric restriction during development or adulthood can cause lifespan extension by increasing mitochondrial activity and prompting the expression of genes involved in stress resistance and longevity [95]. Although pharyngeal pumping is not a direct measure of...
Data
NAC decreased mtDNA replication associated with development. NAC reduced the normal mtDNA copy number increase during 1h exposure. 100μM NAC decrease mtDNA copy number compared to control nematodes after 1h exposure (dark grey vs 1h control). mtDNA copy number increases during nematode development and therefore rises (control 0h vs control 1h). Err...
Data
Sodium azide and potassium cyanide reduced ATP production. Complex IV inhibitors, sodium azide (NaN3) and potassium cyanide (KCn), reduced ATP production. 1mM NaN3 and 50mM KCn reduced in vivo ATP levels measured after 2 minutes of exposure. Statistics were calculated with a two-way ANOVA with replication, compared to the control. * = P<0.05, *** =...
Article
Full-text available
Peroxisomes play an important role in a variety of metabolic pathways, including the α- and β-oxidation of fatty acids, and the biosynthesis of ether phospholipids. Single peroxisomal enzyme deficiencies (PEDs) are a group of peroxisomal disorders in which either a peroxisomal matrix enzyme or a peroxisomal membrane transporter protein is deficient...