Publications by authors named "Michiel Heron"

12 Publications

  • Page 1 of 1

The Usefulness of Two CXCL13 Assays on Cerebrospinal Fluid for the Diagnosis of Lyme Neuroborreliosis: a Retrospective Study in a Routine Clinical Setting.

J Clin Microbiol 2021 Aug 18;59(9):e0025521. Epub 2021 Aug 18.

Centre for Infectious Diseases Research, Diagnostics and Laboratory Surveillance, Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

Recent studies have shown elevated levels of the B-cell chemokine (C-X-C motif) ligand 13 (CXCL13) in the cerebrospinal fluid (CSF) of patients with early Lyme neuroborreliosis (LNB). In this retrospective study, we evaluated the diagnostic performance of the Quantikine CXCL13 enzyme-linked immunosorbent assay (ELISA) (R&D Systems, Inc., MN, USA) and the Bead CXCL13 assay (Mikrogen, Neuried, Germany) for the detection of CXCL13 in CSF. All consecutive patients from whom a CSF and a serum sample had been collected between August 2013 and June 2016 were eligible for inclusion. Patients suspected of LNB were classified as definite, possible, or non-LNB according to the guidelines of the European Federation of Neurological Societies (EFNS). Due to the limited number of LNB patients in the predefined study period, additional LNB patients were included from outside this period. In total, 156 patients (150 consecutive patients and 6 additional LNB patients) were included. Seven (4.5%) were classified as definite, eight (5.1%) as possible, and 141 (90.4%) as non-LNB patients. Receiver operating characteristic (ROC) curve analysis comparing definite-LNB patients with non-LNB patients showed a cutoff value of 85.9 pg/ml for the Quantikine CXCL13 ELISA and 252.2 pg/ml for the Bead CXCL13 assay. The corresponding sensitivity was 100% (95% confidence interval [CI], 100% to 100%) for both, and the corresponding specificities were 98.6% (95% CI, 96.5% to 100%) for the CXCL13 ELISA and 97.2% (95% CI, 93.6% to 100%) for the Bead CXCL13 assay. This study showed that CXCL13 in CSF can be of additional value for the diagnosis of LNB.
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http://dx.doi.org/10.1128/JCM.00255-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373006PMC
August 2021

The clinical relevance of IgM and IgA anti-pneumococcal polysaccharide ELISA assays in patients with suspected antibody deficiency.

Clin Exp Immunol 2021 Aug 1;205(2):213-221. Epub 2021 Jun 1.

Department of Tranzo, Tilburg University, Tilburg, the Netherlands.

Unlike immunoglobulin (Ig)G pneumococcal polysaccharide (PnPS)-antibodies, PnPS IgA and IgM-antibodies are not routinely determined for the assessment of immunocompetence. It is not yet known whether an isolated inability to mount a normal IgM or IgA-PnPS response should be considered a relevant primary antibody deficiency (PAD). We studied the clinical relevance of anti-PnPS IgM and IgA-assays in patients with suspected primary immunodeficiency in a large teaching hospital in 's-Hertogenbosch, the Netherlands. Serotype-specific-PnPS IgG assays were performed; subsequently, 23-valent-PnPS IgG assays (anti-PnPS IgG assays), and later anti-PnPS IgA and IgM assays, were performed in archived material (240 patients; 304 samples). Eleven of 65 pre- and six of 10 post-immunization samples from good responders to PnPS serotype-specific IgG testing had decreased anti-PnPS IgA and/or IgM titres. Of these, three pre- and no post-immunization samples were from patients previously classified as 'no PAD'. Determination of anti-PnPS IgA and IgM in addition to anti-PnPS IgG did not reduce the need for serotype-specific PnPS IgG testing to assess immunocompetence [receiver operating characteristic (ROC) analysis of post-immunization samples: anti-PnPS IgA + IgG area under the curve (AUC) = 0.80, 95% confidence interval (CI) = 0.63-0.97; anti-PnPS IgM + IgG AUC 0.80, 95% CI = 0.62-0.98; anti-PnPS IgA + IgG + IgM AUC = 0.71, 95% CI = 0.51-0.91; anti-PnPS IgG AUC = 0.93, 95% CI = 0.85-1.00]. Our data show that patients classified as having an intact antibody response based on measurement of serotype-specific PnPS IgG can still display impaired anti-PnPS IgM and IgA responses, and that the additional measurement of anti-PnPS IgA and IgM could not reduce the need for serotype-specific IgG testing. Future studies are needed to investigate the clinical relevance of potential 'specific IgA or IgM antibody deficiency' in patients with recurrent airway infections in whom no PAD could be diagnosed according to the current definitions.
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http://dx.doi.org/10.1111/cei.13605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274160PMC
August 2021

Frequencies and clinical associations of myositis-related antibodies in The Netherlands: A one-year survey of all Dutch patients.

J Transl Autoimmun 2019 Dec 23;2:100013. Epub 2019 Aug 23.

Sanquin Diagnostic Services, Amsterdam, the Netherlands.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of connective tissue diseases, collectively known as myositis. Diagnosis of IIM is challenging while timely recognition of an IIM is of utter importance considering treatment options and otherwise irreversible (severe) long-term clinical complications. With the EULAR/ACR classification criteria (2017) considerable advancement has been made in the diagnostic workup of IIM. While these criteria take into account clinical parameters as well as presence of one autoantibody, anti-Jo-1, several autoantibodies are associated with IIM and are currently evaluated to be incorporated into classification criteria. As individual antibodies occur at low frequency, the development of line blots allowing multiplex antibody analysis has improved laboratory diagnostics for IIM. The Euroline myositis line-blot assay (Euroimmun) allows screening and semi-quantitative measurement for 15 autoantibodies, . myositis specific antibodies (MSA) to SRP, EJ, OJ, Mi-2α, Mi-2β, TIF1-γ, MDA5, NXP2, SAE1, PL-12, PL-7, Jo-1 and myositis associated antibodies (MAA) to Ku, PM/Scl-75 and PM/Scl-100. To evaluate the clinical significance of detection and levels of these autoantibodies in the Netherlands, a retrospective analysis of all Dutch requests for extended myositis screening within a 1 year period was performed. A total of 187 IIM patients and 632 non-IIM patients were included. We conclude that frequencies of MSA and MAA observed in IIM patients in a routine diagnostic setting are comparable to cohort-based studies. Weak positive antibody levels show less diagnostic accuracy compared to positive antibody levels, except for anti-NXP2. Known associations between antibodies and skin involvement (anti-MDA5, anti-TIF1-γ), lung involvement (anti-Jo-1), and malignancy (anti-TIF1-γ) were confirmed in our IIM study population. The availability of multiplex antibody analyses will facilitate inclusion of additional autoantibodies in clinical myositis guidelines and help to accelerate diagnosing IMM with rare but specific antibodies.
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http://dx.doi.org/10.1016/j.jtauto.2019.100013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388388PMC
December 2019

Focusing on Good Responders to Pneumococcal Polysaccharide Vaccination in General Hospital Patients Suspected for Immunodeficiency. A Decision Tree Based on the 23-Valent Pneumococcal IgG Assay.

Front Immunol 2019 5;10:2496. Epub 2019 Nov 5.

Department of Tranzo, Tilburg University, Tilburg, Netherlands.

Recently, the 23-valent IgG-assay was suggested as screening assay to identify responders to pneumococcal polysaccharide (PnPS)-vaccination with the serotype-specific assay as a second-line test. However, in a low pre-test probability general hospital setting predicting responders could be more valuable to reduce the number of samples needing serotyping. Serotype-specific PnPS antibody-assays were performed for suspected immunodeficiency in two Dutch general hospitals (Jeroen Bosch Hospital, 's-Hertogenbosch; Elisabeth Tweesteden Hospital, Tilburg). 23-Valent PnPS antibody-assays were subsequently performed in archived material. Data were analyzed using receiver operating characteristic curves (AUC) and agreement indices (ICC). Sera of 284 patients (348 samples) were included; 23-valent IgG-titres and the corresponding sum of PnPS-serotype specific antibodies showed moderate correlation (ICC = 0.63). In 232 conjugated-pneumococcal-vaccine-naïve patients (270 samples), a random 23-valent IgG-titer could discriminate between samples with and without ≥7/11, ≥7/13, or ≥6/9 pneumococcal serotypes when both cut-off values 0.35 and 1.0 μg/ml were used (AUC 0.86 and 0.92, respectively). All patients with a pre-immunization-titer ≥38.2 μg/ml and/or post-immunization-titer ≥96.1 μg/ml and none with a post-immunization-titer ≤38.5 μg/ml exhibited a good response to PnPS vaccination. Using these breakpoints as screening test to predict responders, only 24% of patients would require further serotyping, as opposed to 68% if breakpoints to predict responders would have been used. In a low pre-test probability setting, the 23-valent IgG-assay proved to be a reliable screening test for good responders in conjugated-pneumococcal-vaccine-naïve patients, reducing the overall number of patient samples needing further serotyping, thus reducing overall costs of pneumococcal vaccination response assessment.
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http://dx.doi.org/10.3389/fimmu.2019.02496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848064PMC
November 2020

Deciphering the genotype and phenotype of hairy cell leukemia: clues for diagnosis and treatment.

Expert Rev Clin Immunol 2019 08 12;15(8):857-867. Epub 2019 Jul 12.

a Department of Sciences, University College Roosevelt , Middelburg , The Netherlands.

: Hairy cell leukemia (HCL) is a rare, indolent B-cell neoplasm. The classical variant of the disease is characterized by the V600E mutation, which is present in virtually all cases. How this mutation leads to the signs and symptoms of the disease is currently not known. : This review explores the genetic background of HCL, especially the V600E driver mutation, but passenger mutations and their effects are also included. The clinical significance of mutations in other cancer types is discussed, as well as - induced senescence. An overview of the major forms of treatment of HCL (cytostatic drugs, specific BRAF inhibitors, B cell-specific antibodies) is given. Finally, possible mechanisms of the monocytopenia and hairy morphology so typical of this disease are discussed. : Although being a rare disease, HCL and its pathogenesis can yield important information about -related cancer metabolism. Many aspects of the disease are still unclear, but with the right resources, this could change. This can lead to a more efficient and specific treatment, thus leading to decreased morbidity.
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http://dx.doi.org/10.1080/1744666X.2019.1641405DOI Listing
August 2019

The diagnostic value of component-resolved diagnostics in peanut allergy in children attending a Regional Paediatric Allergology Clinic.

BMC Pediatr 2016 06 2;16:74. Epub 2016 Jun 2.

Department of Paediatric Allergology, Reinier de Graaf Hospital, Delft, PO Box 5011, 2600, GA, The Netherlands.

Background: To date, diagnosing food allergies in children still presents a diagnostic dilemma, leading to uncertainty concerning the definite diagnosis of peanut allergy, as well as to the need for strict diets and the potential need for adrenalin auto-injectors. This uncertainty in particular is thought to contribute to a lower quality of life. In the diagnostic process double-blind food challenges are considered the gold standard, but they are time-consuming as well as potentially hazardous. Other diagnostic tests have been extensively studied and among these component-resolved diagnostics appeared to present a promising alternative: Ara h2, a peanut storage protein in previous studies showed to have a significant predictive value.

Methods: Sixty-two out of 72 children, with suspected peanut allergy were analyzed using serum specific IgE and/or skin prick tests and specific IgE to several components of peanut (Ara h 1, 2, 3, 6, 8, 9). Subsequently, double-blind food challenges were performed. The correlation between the various diagnostic tests and the overall outcome of the double-blind food challenges were studied, in particular the severity of the reaction and the eliciting dose.

Results: The double-blind provocation with peanut was positive in 33 children (53 %). There was no relationship between the eliciting dose and the severity of the reaction. A statistically significant relationship was found between the skin prick test, specific IgE directed to peanut, Ara h 1, Ara h 2 or Ara h 6, and the outcome of the food challenge test, in terms of positive or negative (P < .001). However, we did not find any relationship between sensitisation to peanut extract or the different allergen components and the severity of the reaction or the eliciting dose. There was no correlation between IgE directed to Ara h 3, Ara h 8, Ara h 9 and the clinical outcome of the food challenge.

Conclusions: This study shows that component-resolved diagnostics is not superior to specific IgE to peanut extract or to skin prick testing. At present, it cannot replace double-blind placebo-controlled food challenges for determination of the eliciting dose or the severity of the peanut allergy in our patient group.
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http://dx.doi.org/10.1186/s12887-016-0609-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891901PMC
June 2016

Translating the MDS flow cytometric score into clinical practice.

Cytometry B Clin Cytom 2015 May-Jun;88(3):207-9. Epub 2014 Dec 10.

Medical Laboratories, Department of Immunology, Reinier de Graaf Groep, Delft, The Netherlands.

Myelodysplastic syndromes (MDS) are classified by the WHO as myeloid neoplasms, and are characterized by cytopenia and dysplasia in one or more myeloid cell lines. Recently, a flow cytometric score (FCM-score) was published capable of discriminating low-grade MDS from non-clonal cytopenias (Della Porta et al., 2012). We tested the applicability of the FCM-score in a patient population from a large peripheral teaching hospital in The Netherlands. The evaluation of the proposed FCM score in low-grade MDS showed a high sensitivity and specificity, and clinically significant positive and negative likelihood ratios. The use of CD10 and CD19 positivity to identify progenitor B-cell blasts provided a specific and precize method to separate progenitor B-cell blasts from myeloid blasts within the CD34+/low CD45+ population and may be more convenient compared to the published method using low SSC and CD45 expression. This study confirms the value of utilizing the FCM-score in our patient population.
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http://dx.doi.org/10.1002/cyto.b.21208DOI Listing
January 2016

Serum and BALF YKL-40 levels are predictors of survival in idiopathic pulmonary fibrosis.

Respir Med 2011 Jan;105(1):106-13

Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands.

Background: The chitinase-like protein YKL-40 is a serum biomarker in diseases with fibrosis, inflammation and tissue remodelling. Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that is hallmarked by these processes. The aim of this study was to investigate the potential of YKL-40 as a prognostic biomarker for survival in IPF patients.

Methods: Serum and bronchoalveolar lavage fluid (BALF) levels of YKL-40 at the time of diagnosis and a promoter polymorphism in CHI3L1, the gene encoding YKL-40, were determined in 85 IPF patients and 126 controls. The relationship between YKL-40 levels and clinical parameters was evaluated. Kaplan-Meier and Cox regression analyses were used to examine the association between YKL-40 levels and survival.

Results: Serum and BALF YKL-40 levels were significantly higher in patients than in healthy controls (p < 0.001). The - 329 A/G polymorphism had a significant influence on BALF YKL-40 levels and the influence on serum YKL-40 levels showed a trend towards significance in IPF patients. IPF patients with high (> 79 ng/ml) serum or high BALF YKL-40 (> 17 ng/ml) levels had significantly shorter survival than those with low YKL-40 levels in serum or BALF. In patients with both low serum and low BALF YKL-40 levels no IPF related mortality was observed. Cox regression modelling showed that there were no confounding factors.

Conclusions: The - 329 polymorphism was associated with serum and BALF YKL-40 levels in IPF patients. High serum and BALF YKL-40 levels are associated with poor survival in IPF patients and could be useful prognostic markers for survival in IPF.
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http://dx.doi.org/10.1016/j.rmed.2010.09.012DOI Listing
January 2011

Increased expression of CD16, CD69, and very late antigen-1 on blood monocytes in active sarcoidosis.

Chest 2008 Nov 18;134(5):1001-1008. Epub 2008 Jul 18.

Center for Interstitial Lung Diseases, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands.

Background: Different types of immune cells are involved in the formation of granulomas, a hallmark of pulmonary sarcoidosis. Proinflammatory monocytes are activated circulating monocytes thought to be related to the initial events of granuloma formation. We tested the hypothesis that peripheral blood monocytes in patients with active pulmonary sarcoidosis have an activated phenotype and, secondly, that measuring this activation status can provide a new tool for monitoring disease activity.

Methods: Blood was collected of 23 steroid-naive patients presenting with pulmonary sarcoidosis and 10 healthy control subjects. Expression of CD16 (Fc-gamma type III receptor), CD69 (a general activation marker of cells of the hematopoietic lineage), and the integrin very late antigen (VLA)-1 (on interaction with extracellular matrix compounds mediates cell adhesion) was measured by flow cytometry.

Results: Percentages of monocytes expressing CD16, CD69, and VLA-1 in patients vs control subjects were 56.2 +/- 4.1% vs 12.2 +/- 2.4% (p < 0.0001), 87.3 +/- 2.1% vs 8.6 +/- 3.3% (p < 0.0001), and 66.5 +/- 3.6% vs 11.2 +/- 2.3% (p < 0.0001), respectively. Moreover, the CD69+VLA-1+ monocyte subset, abundantly present at disease presentation, was found to decrease to normal levels during follow-up with disease remission.

Conclusions: Peripheral blood monocytes from patients with pulmonary sarcoidosis show a highly activated phenotype. Phenotyping circulating monocytes might be a promising tool for monitoring sarcoidosis disease activity but needs further investigation.
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http://dx.doi.org/10.1378/chest.08-0443DOI Listing
November 2008

Evaluation of CD103 as a cellular marker for the diagnosis of pulmonary sarcoidosis.

Clin Immunol 2008 Mar 8;126(3):338-44. Epub 2008 Jan 8.

Center for Interstitial Lung Diseases, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, The Netherlands.

A high CD4(+)/CD8(+) ratio in bronchoalveolar lavage fluid is indicative for the diagnosis pulmonary sarcoidosis but this ratio only does not fully discriminate pulmonary sarcoidosis from other interstitial lung diseases. Recently, the integrin CD103 has been implicated in the diagnostic evaluation of sarcoidosis. CD103 is expressed on intraepithelial lymphocytes in mucosal areas, including bronchi, and is possibly involved in the retention of lymphocytes to the mucosa. The Dutch BAL working party initiated an investigation to evaluate the diagnostic value of relative number of CD103 expressing CD4(+) T-lymphocytes in the BAL fluid of patients with a variety of interstitial lung diseases. The expression of CD103 was examined on bronchoalveolar lavage cells from 119 patients including 56 patients with pulmonary sarcoidosis. We redefined criteria for alveolar CD4(+) T-cell lymphocytosis and for the relative enumeration of CD103 expressing CD4(+) T-lymphocytes in the BAL fluid. Our data demonstrate that the combined use of the CD103(+)CD4(+)/CD4(+) ratio (<0.2) and the BAL CD4(+)/CD8(+) ratio (>3) or the relative alveolitis CD4(+)/CD8(+) BAL/PB ratio (>2) provides a specific tool for discriminating sarcoidosis, also without a clear CD4(+) alveolitis, from other interstitial lung diseases.
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http://dx.doi.org/10.1016/j.clim.2007.11.005DOI Listing
March 2008

Invariant natural killer T cells in obstructive pulmonary diseases.

N Engl J Med 2007 Jul;357(2):194; author reply 194-5

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July 2007
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