10 results on '"Laar, Jan A. M."'
Search Results
2. Leukocyte toll-like receptor expression in pathergy positive and negative Behçet's disease patients.
- Author
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van der Houwen TB, Dik WA, Goeijenbier M, Hayat M, Nagtzaam NMA, van Hagen M, and van Laar JAM
- Subjects
- Adult, B-Lymphocytes metabolism, Behcet Syndrome pathology, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes metabolism, Case-Control Studies, Female, Flow Cytometry, Humans, Male, Middle Aged, Toll-Like Receptor 1 metabolism, Toll-Like Receptor 2 metabolism, Toll-Like Receptor 4 metabolism, Young Adult, Behcet Syndrome metabolism, Toll-Like Receptors metabolism
- Abstract
Objectives: To investigate whether the auto-inflammatory nature and the pathergic reaction in Behçet's disease (BD) are driven by a disturbed toll-like receptor (TLR) response., Methods: We compared both TLR expression by flow-cytometry and TLR response by stimulation assay in 18 BD patients (both pathergy positive and pathergy negative) with 15 healthy controls., Results: Expression of TLR1 and 2 was significantly elevated in B-lymphocytes of BD patients compared with healthy controls. TLR1, 2 and 4 were significantly more highly expressed in both CD4+ and CD8+ T-lymphocytes of BD patients. Granulocytes of BD patients displayed significantly higher expression of TLR1, 2, 4 and 6. TLR2, 4 and 5 expression was significantly increased on classical monocytes of BD patients. Intermediate monocytes of BD patients showed an increase in expression of TLR2. Furthermore, TLR2 and 5 were significantly more highly expressed in non-classical monocytes of BD patients. In pathergy positive patients, TLR5 was even more highly expressed compared with pathergy negative patients on B- and T-lymphocytes and granulocytes. Furthermore, TLR2 and 5 showed an elevated TNF-α response to stimulation with their cognate ligands., Conclusion: Immune cells of BD patients overexpress TLR1, 2, 4, 5 and 6. Furthermore, after stimulation of TLR2 and 5, BD patients demonstrate a more potent TNF-α response. Although this is a small cohort, in the pathergy positive patients, TLR5 expression is even further augmented, suggesting that a microbial (flagellin) or damage (HMGB1) associated signal may trigger the exaggerated immune response that is characteristic for the pathergy phenomenon in BD. In conclusion, these results point to an exaggerated TLR response in the auto-inflammatory nature of BD., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
- Published
- 2020
- Full Text
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3. MxA is a clinically applicable biomarker for type I interferon activation in systemic lupus erythematosus and systemic sclerosis.
- Author
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Huijser E, van Helden-Meeuwsen CG, Groot N, Bodewes ILA, Wahadat MJ, Schreurs MWJ, van Daele PLA, Dalm VASH, van Laar JAM, van Hagen PM, Waris M, Kamphuis S, and Versnel MA
- Subjects
- Biomarkers blood, Case-Control Studies, Humans, Interferon Type I immunology, Lupus Erythematosus, Systemic immunology, Myxovirus Resistance Proteins blood, Scleroderma, Systemic immunology
- Published
- 2019
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4. Can epidemiological studies uncover the origin of Behçet's disease?
- Author
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van Laar JAM
- Subjects
- Humans, Behcet Syndrome, Epidemiologic Studies
- Published
- 2018
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5. To distinguish IgG4-related disease from seronegative granulomatosis with polyangiitis.
- Author
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Karim AF, Verdijk RM, Nagtegaal AP, Bansie R, Paridaens D, van Hagen PM, and van Laar JAM
- Subjects
- Aged, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Granulomatosis with Polyangiitis diagnosis, Immunoglobulin G blood, Immunoproliferative Disorders diagnosis
- Published
- 2017
- Full Text
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6. Chronic signs of memory B cell activation in patients with Behçet's disease are partially restored by anti-tumour necrosis factor treatment.
- Author
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van der Houwen TB, van Hagen PM, Timmermans WM, Bartol SJ, Lam KH, Kappen JH, van Zelm MC, and van Laar JA
- Subjects
- Adalimumab therapeutic use, Adult, Aged, Antirheumatic Agents therapeutic use, B-Lymphocyte Subsets metabolism, B-Lymphocytes metabolism, Behcet Syndrome complications, Behcet Syndrome drug therapy, Behcet Syndrome metabolism, Case-Control Studies, Female, Flow Cytometry, Humans, Immunoglobulin A immunology, Immunoglobulin Class Switching, Immunoglobulin D immunology, Immunoglobulin G immunology, Immunoglobulin M immunology, Immunohistochemistry, Male, Middle Aged, Somatic Hypermutation, Immunoglobulin, Tumor Necrosis Factor Receptor Superfamily, Member 7 metabolism, Tumor Necrosis Factor-alpha antagonists & inhibitors, Ulcer etiology, Ulcer metabolism, Young Adult, B-Lymphocyte Subsets immunology, B-Lymphocytes immunology, Behcet Syndrome immunology, Immunologic Memory immunology, Ulcer immunology
- Abstract
Objectives: Behçet's disease (BD), an auto-inflammatory vasculitis with oro-genital ulcerations, skin lesions and uveitis, is regarded as T cell mediated. A successful trial with rituximab suggests an additive role for B cells in the pathogenesis. Therefore, we studied B cell abnormalities in BD patients and the effect of TNF-blocking therapy., Methods: B cells in blood (n = 36) and tissue (n = 6) of BD patients were analysed with flow cytometry and/or immunohistochemistry and compared with healthy controls (n = 22). BD current activity form (BDCAF) in relation to B cell somatic hypermutations (SHMs) and immunoglobulin class-switching were studied., Results: Thirty-six patients (17 males) were included, mean age 44 years, average disease duration 10 years and mean BDCAF 2.7. Blood B cell numbers were significantly lower in patients than in controls (P = 0.0061), mostly due to decreased CD27
+ memory B cells expressing IgM (P = 0.0001), IgG (P = 0.0002) and IgA (P = 0.0038) B cell subsets. CD27+ IgA+ B cells showed the highest magnitude of decrease in active disease, measured with BDCAF (P = 0.02). CD27+ IgM+ IgD+ B cells were impaired in replication history (P = 0.0133) and selection of SHM, whereas IgA+ B cells carried elevated SHM levels (P = 0.04) and lower IgA2 subclass usage (P = 0.0004) than controls. Immunohistochemistry revealed B cells in tissue of active mucosal ulcers. In adalimumab-treated patients, blood B cells were similar to controls., Conclusion: We show significant deviations in the memory B cell compartment, related to disease activity and therapeutic efficacy. Pronounced molecular impairments were seen in the fast-responding IgM+ -memory and the mucosal IgA+ -memory B cells. Because of the demonstrated abundance of B cells in affected tissue, we hypothesize relocation of memory B cells to the site of inflammation could account for the deviations found in blood of BD patients. These peripheral B cells are easily accessible as a marker to monitor therapeutic efficacy., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)- Published
- 2017
- Full Text
- View/download PDF
7. Suggested Relationship Between Hemophagocytic Lymphohistiocytosis and Bartonella henselae.
- Author
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Rokx C, van Laar JA, and Rijnders BJ
- Subjects
- Antibodies, Bacterial, Humans, Polymerase Chain Reaction, Bartonella henselae genetics, Lymphohistiocytosis, Hemophagocytic
- Published
- 2016
- Full Text
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8. Prevalence of distal renal tubular acidosis in primary Sjögren's syndrome.
- Author
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Both T, Hoorn EJ, Zietse R, van Laar JA, Dalm VA, Brkic Z, Versnel MA, van Hagen PM, and van Daele PL
- Subjects
- Acidosis, Renal Tubular immunology, Aged, Ammonium Chloride, Antibodies, Antinuclear blood, Cohort Studies, Cross-Sectional Studies, Female, Fludrocortisone, Furosemide, Humans, Hydrogen-Ion Concentration, Male, Mass Screening methods, Middle Aged, Prevalence, Acidosis, Renal Tubular diagnosis, Acidosis, Renal Tubular epidemiology, Sjogren's Syndrome complications
- Abstract
Objectives: Our objectives were to analyse the prevalence of distal renal tubular acidosis (dRTA) in primary SS (pSS) and to compare a novel urinary acidification test with furosemide and fludrocortisone (FF) with the gold standard ammonium chloride (NH4Cl) to detect dRTA., Methods: Urinary acidification was assessed in 57 pSS patients using NH4Cl and FF. A urinary acidification defect was defined as an inability to reach a urinary pH of <5.3 after NH4Cl., Results: The prevalence of complete dRTA (urinary acidification defect with acidosis) was 5% (3/57). All three patients had positive SSA/Ro and SSB/La autoantibodies and impaired kidney function. The prevalence of incomplete dRTA (urinary acidification defect without acidosis) was 25% (14/57). Compared with patients without dRTA, patients with incomplete dRTA had significantly lower venous pH and serum bicarbonate and higher urinary pH. SSB/La antibodies were more prevalent in the dRTA groups (P < 0.05). Compared with NH4Cl, the positive and negative predictive values of FF were 46% and 82%, respectively. Vomiting occurred more often during the urinary acidification test with NH4Cl than with FF (9 vs 0, P < 0.05)., Conclusion: Incomplete dRTA is common in pSS and causes mild acidaemia and higher urinary pH, which may contribute to bone demineralization and kidney stone formation. FF cannot replace NH4Cl in testing urinary acidification in pSS, but may be considered as a screening tool, given its reasonable negative predictive value and better tolerability., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2015
- Full Text
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9. Utility of contrast-enhanced ultrasound for the assessment of the carotid artery wall in patients with Takayasu or giant cell arteritis.
- Author
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Schinkel AF, van den Oord SC, van der Steen AF, van Laar JA, and Sijbrands EJ
- Subjects
- Adult, Aged, Carotid Arteries pathology, Carotid Intima-Media Thickness, Contrast Media, Female, Giant Cell Arteritis pathology, Humans, Male, Middle Aged, Pilot Projects, Prospective Studies, Takayasu Arteritis pathology, Carotid Arteries diagnostic imaging, Giant Cell Arteritis diagnostic imaging, Takayasu Arteritis diagnostic imaging
- Abstract
Aims: Carotid contrast-enhanced ultrasound (CEUS) was recently proposed for the evaluation of large-vessel vasculitides (LVV), particularly to assess vascularization within the vessel wall. The aim of this pilot study was to evaluate the potential of carotid colour Doppler ultrasound (CDUS) and CEUS in patients with LVV., Methods and Results: This prospective study included seven patients (mean age 48 ± 14 years, all females) with established LVV (Takayasu arteritis or giant cell arteritis). All patients underwent CDUS and CEUS (14 carotid arteries). Intima-media thickness, lumen diameter, Doppler velocities, vessel wall thickening, and lesion thickness were assessed. CEUS was used to improve visualization of the lumen-to-vessel wall border, and to visualize carotid wall vascularization. Four (57%) patients [7 (50%) carotid arteries] exhibited lesions, and the average lesion thickness was 2.0 ± 0.5 mm. According to the Doppler peak systolic velocity, 5 (35%) carotid arteries had a <50% stenosis, 1 (7%) had a 50-70% stenosis, and 1 (7%) had a ≥70% stenosis. The contrast agent improved the image quality and the definition of the lumen-to-vascular wall border. Carotid wall vascularization was observed in 5 (71%) patients [9 (64%) carotid arteries]. Five (36%) carotid arteries had mild-to-moderate vascularization, and 4 (29%) had severe wall vascularization., Conclusion: Carotid CDUS allows the assessment of anatomical features of LVV, including vessel wall thickening and degree of stenosis. Carotid CEUS improves the visualization of the lumen border, and allows dynamic assessment of carotid wall vascularization, which is a potential marker of disease activity in patients with LVV.
- Published
- 2014
- Full Text
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10. Low prevalence of NOD2 SNPs in Behçet's disease suggests protective association in Caucasians.
- Author
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Kappen JH, Wallace GR, Stolk L, Rivadeneira F, Uitterlinden AG, van Daele PL, Laman JD, Kuijpers RW, Baarsma GS, Stanford MR, Fortune F, Madanat W, van Hagen PM, and van Laar JA
- Subjects
- Aged, Behcet Syndrome prevention & control, Cohort Studies, Gene Frequency, Genetic Predisposition to Disease, Genotype, Heterozygote, Humans, Middle Aged, White People genetics, Behcet Syndrome genetics, Nod2 Signaling Adaptor Protein genetics, Polymorphism, Single Nucleotide
- Abstract
Objective: It has been shown previously that three nucleotide-binding oligomerization domain containing 2 (NOD2) variants (Arg702Trp, Gly908Arg and Lue1007fs) are associated with Crohn's disease (CD), a disorder clinically resembling Behçet's disease (BD). We studied the frequency of these variants in BD patients., Methods: DNA samples of 200 BD patients [59 Caucasians, 139 Middle Easterns (MEs) of Arab descent and 2 Asians] and 520 healthy controls (444 Caucasians and 76 MEs) were genotyped using a Taqman assay., Results: Both the Arg702Trp and Leu1007fs (frameshift) variants were significantly less frequently present among BD patients compared with healthy controls (0.5 vs 5.8%; P < 1.10(-5) and 0.0 vs 1.8%; P < 0.007, respectively). In the Caucasian subpopulation, Arg702Trp was significantly less frequent in the BD group as compared with the controls (P = 0.04); whereas in the ME subpopulation, a trend was observed (P < 0.06)., Conclusions: Of the three CD-associated single nucleotide polymorphisms, one of the variant NOD2 alleles, was found to be present significantly less in Caucasian BD patients.
- Published
- 2009
- Full Text
- View/download PDF
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