Publications by authors named "Heidi Lemmers"

16 Publications

  • Page 1 of 1

Seasonal and Nonseasonal Longitudinal Variation of Immune Function.

J Immunol 2021 07 14;207(2):696-708. Epub 2021 Jul 14.

Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Gelderland, the Netherlands;

Different components of the immune response show large variability between individuals, but they also vary within the same individual because of host and environmental factors. In this study, we report an extensive analysis of the immune characteristics of 56 individuals over four timepoints in 1 single year as part of the Human Functional Genomics Project. We characterized 102 cell subsets using flow cytometry; quantified production of eight cytokines and two chemokines in response to 20 metabolic, bacterial, fungal, and viral stimuli; and measured circulating markers of inflammation. Taking advantage of the longitudinal sampling, both seasonal and nonseasonal sources of variability were studied. The circulating markers of inflammation IL-18, IL-18 binding protein, and resistin displayed clear seasonal variability, whereas the strongest effect was observed for α-1 antitrypsin. Cytokine production capacity also showed strong seasonal changes, especially after stimulation with the influenza virus, , and Furthermore, we observed moderate seasonality effects on immune cell counts, especially in several CD4/CD8 T cell subpopulations. Age of the volunteers was an important factor influencing IFN-γ and IL-22 production, which matched the strong impact of age on several T cell subsets. Finally, on average, genetics accounted for almost 50% of the interindividual variance not already explained by age, sex, and body mass index, although this varies strongly for different parameters. In conclusion, seasonality is an important environmental factor that influences immune responses, in addition to specific genetic and nongenetic host factors, and this may well explain the seasonal variation in the incidence and severity of immune-mediated diseases.
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http://dx.doi.org/10.4049/jimmunol.2000133DOI Listing
July 2021

induction of trained immunity in adherent human monocytes.

STAR Protoc 2021 Mar 24;2(1):100365. Epub 2021 Feb 24.

Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, 6500HB Nijmegen, the Netherlands.

A growing number of studies show that innate immune cells can undergo functional reprogramming, facilitating a faster and enhanced response to heterologous secondary stimuli. This concept has been termed "trained immunity." We outline here a protocol to recapitulate this using adherent monocytes from consecutive isolation of peripheral blood mononuclear cells. The induction of trained immunity and the associated functional reprogramming of monocytes is described in detail using β-glucan (from ) and Bacillus Calmette-Guérin as examples. For complete details on the use and execution of this protocol, please refer to Repnik et al. (2003) and Bekkering et al. (2016).
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http://dx.doi.org/10.1016/j.xpro.2021.100365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921712PMC
March 2021

Thyrotrophin and thyroxine support immune homeostasis in humans.

Immunology 2021 06 7;163(2):155-168. Epub 2021 Feb 7.

Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, The Netherlands.

The endocrine and the immune systems interact by sharing receptors for hormones and cytokines, cross-control and feedback mechanisms. To date, no comprehensive study has assessed the impact of thyroid hormones on immune homeostasis. By studying immune phenotype (cell populations, antibody concentrations, circulating cytokines, adipokines and acute-phase proteins, monocyte-platelet interactions and cytokine production capacity) in two large independent cohorts of healthy volunteers of Western European descent from the Human Functional Genomics Project (500FG and 300BCG cohorts), we identified a crucial role of the thyroid hormone thyroxin (T4) and thyroid-stimulating hormone (TSH) on the homeostasis of lymphocyte populations. TSH concentrations were strongly associated with multiple populations of both effector and regulatory T cells, whereas B-cell populations were significantly associated with free T4 (fT4). In contrast, fT4 and TSH had little impact on myeloid cell populations and cytokine production capacity. Mendelian randomization further supported the role of fT4 for lymphocyte homeostasis. Subsequently, using a genomics approach, we identified genetic variants that influence both fT4 and TSH concentrations and immune responses, and gene set enrichment pathway analysis showed enrichment of fT4-affected gene expression in B-cell function pathways, including the CD40 pathway, further supporting the importance of fT4 in the regulation of B-cell function. In conclusion, we show that thyroid function controls the homeostasis of the lymphoid cell compartment. These findings improve our understanding of the immune responses and open the door for exploring and understanding the role of thyroid hormones in the lymphocyte function during disease.
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http://dx.doi.org/10.1111/imm.13306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114202PMC
June 2021

Circadian rhythm influences induction of trained immunity by BCG vaccination.

J Clin Invest 2020 10;130(10):5603-5617

Radboud Center for Infectious Diseases and Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands.

BACKGROUNDThe antituberculosis vaccine bacillus Calmette-Guérin (BCG) reduces overall infant mortality. Induction of innate immune memory, also termed trained immunity, contributes toward protection against heterologous infections. Since immune cells display oscillations in numbers and function throughout the day, we investigated the effect of BCG administration time on the induction of trained immunity.METHODSEighteen volunteers were vaccinated with BCG at 6 pm and compared with 36 age- and sex-matched volunteers vaccinated between 8 am and 9 am. Peripheral blood mononuclear cells were stimulated with Staphylococcus aureus and Mycobacterium tuberculosis before, as well as 2 weeks and 3 months after, BCG vaccination. Cytokine production was measured to assess the induction of trained immunity and adaptive responses, respectively. Additionally, the influence of vaccination time on induction of trained immunity was studied in an independent cohort of 302 individuals vaccinated between 8 am and 12 pm with BCG.RESULTSCompared with evening vaccination, morning vaccination elicited both a stronger trained immunity and adaptive immune phenotype. In a large cohort of 302 volunteers, early morning vaccination resulted in a superior cytokine production capacity compared with later morning. A cellular, rather than soluble, substrate of the circadian effect of BCG vaccination was demonstrated by the enhanced capacity to induce trained immunity in vitro in morning- compared with evening-isolated monocytes.CONCLUSIONSBCG vaccination in the morning induces stronger trained immunity and adaptive responses compared with evening vaccination. Future studies should take vaccine administration time into account when studying specific and nonspecific effects of vaccines; early morning should be the preferred moment of BCG administration.FUNDINGThe Netherlands Organization for Scientific Research, the European Research Council, and the Danish National Research Foundation.
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http://dx.doi.org/10.1172/JCI133934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641012PMC
October 2020

BCG vaccination in humans inhibits systemic inflammation in a sex-dependent manner.

J Clin Invest 2020 10;130(10):5591-5602

Radboud Center for Infectious Diseases and.

BACKGROUNDInduction of innate immune memory, also termed trained immunity, by the antituberculosis vaccine bacillus Calmette-Guérin (BCG) contributes to protection against heterologous infections. However, the overall impact of BCG vaccination on the inflammatory status of an individual is not known; while induction of trained immunity may suggest increased inflammation, BCG vaccination has been epidemiologically associated with a reduced incidence of inflammatory and allergic diseases.METHODSWe investigated the impact of BCG (BCG-Bulgaria, InterVax) vaccination on systemic inflammation in a cohort of 303 healthy volunteers, as well as the effect of the inflammatory status on the response to vaccination. A targeted proteome platform was used to measure circulating inflammatory proteins before and after BCG vaccination, while ex vivo Mycobacterium tuberculosis- and Staphylococcus aureus-induced cytokine responses in peripheral blood mononuclear cells were used to assess trained immunity.RESULTSWhile BCG vaccination enhanced cytokine responses to restimulation, it reduced systemic inflammation. This effect was validated in 3 smaller cohorts, and was much stronger in men than in women. In addition, baseline circulating inflammatory markers were associated with ex vivo cytokine responses (trained immunity) after BCG vaccination.CONCLUSIONThe capacity of BCG to enhance microbial responsiveness while dampening systemic inflammation should be further explored for potential therapeutic applications.FUNDINGNetherlands Organization for Scientific Research, European Research Council, and the Danish National Research Foundation.
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http://dx.doi.org/10.1172/JCI133935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524503PMC
October 2020

BCG-Induced Trained Immunity in Healthy Individuals: The Effect of Plasma Muramyl Dipeptide Concentrations.

J Immunol Res 2020 15;2020:5812743. Epub 2020 Jun 15.

Department of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, 6525 Nijmegen, Netherlands.

BCG vaccination protects not only against tuberculosis but also against heterologous infections. This effect differs between individuals, yet the factors responsible for this variation are unknown. BCG-induced nonspecific protection is, at least partially, mediated by innate immune reprogramming (trained immunity), which can be induced by the muramyl dipeptide (MDP) component of peptidoglycans. We aimed to study whether differential release of MDP in healthy individuals may explain variability of their response to BCG vaccination. Circulating MDP concentrations were increased up to three months after BCG vaccination. MDP concentrations at baseline, but not their increase postvaccination, positively correlated with the induction of trained immunity and not with mycobacteria-induced T-cell responses. Interestingly, MDP concentrations correlated with inflammatory markers in the circulation. In conclusion, circulating MDP concentrations are associated with the strength of trained immunity responses and thus influence the biological effects of BCG vaccination. This study increases our understanding about the role of MDP in BCG-induced trained immunity, which might help to optimize vaccine efficacy and explore novel applications of BCG vaccination.
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http://dx.doi.org/10.1155/2020/5812743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312554PMC
May 2021

Sex-Specific Regulation of Inflammation and Metabolic Syndrome in Obesity.

Arterioscler Thromb Vasc Biol 2020 07 28;40(7):1787-1800. Epub 2020 May 28.

From the Department of Internal Medicine and Radboud Institute for Molecular Life Sciences (R.t.H., I.C.L.v.d.M., K.S., M.J., S.P.S., T.B., H.L., H.D., J.d.G., L.A.B.J., J.H.W.R., M.G.N., N.P.R.), Radboud University Medical Center, Nijmegen, the Netherlands.

Objective: Metabolic dysregulation and inflammation are important consequences of obesity and impact susceptibility to cardiovascular disease. Anti-inflammatory therapy in cardiovascular disease is being developed under the assumption that inflammatory pathways are identical in women and men, but it is not known if this is indeed the case. In this study, we assessed the sex-specific relation between inflammation and metabolic dysregulation in obesity. Approach and Results: Three hundred two individuals were included, half with a BMI 27 to 30 kg/m and half with a BMI>30 kg/m, 45% were women. The presence of metabolic syndrome was assessed according to the National Cholesterol Education Program-ATPIII criteria, and inflammation was studied using circulating markers of inflammation, cell counts, and ex vivo cytokine production capacity of isolated immune cells. Additionally, lipidomic and metabolomic data were gathered, and subcutaneous fat biopsies were histologically assessed. Metabolic syndrome is associated with an increased inflammatory profile that profoundly differs between women and men: women with metabolic syndrome show a lower concentration of the anti-inflammatory adiponectin, whereas men show increased levels of several pro-inflammatory markers such as IL (interleukin)-6 and leptin. Adipose tissue inflammation showed similar sex-specific associations with these markers. Peripheral blood mononuclear cells isolated from men, but not women, with metabolic syndrome display enhanced cytokine production capacity.

Conclusions: We identified sex-specific pathways that influence inflammation in obesity. Excessive production of proinflammatory cytokines was observed in men with metabolic syndrome. In contrast, women typically showed reduced levels of the anti-inflammatory adipokine adiponectin. These different mechanisms of inflammatory dysregulation between women and men with obesity argue for sex-specific therapeutic strategies.
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http://dx.doi.org/10.1161/ATVBAHA.120.314508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310302PMC
July 2020

The Inter-Relationship of Platelets with Interleukin-1β-Mediated Inflammation in Humans.

Thromb Haemost 2018 Dec 19;118(12):2112-2125. Epub 2018 Nov 19.

Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.

Background:  Inflammation and coagulation are key processes in cardiovascular diseases (CVDs). The Canakinumab Anti-inflammatory Thrombosis Outcome Study trial affirmed the importance of inflammation in CVD by showing that inhibition of the interleukin (IL)-1β pathway prevents recurrent CVD. A bi-directional relationship exists between inflammation and coagulation, but the precise interaction of platelets and IL-1β-mediated inflammation is incompletely understood. We aimed to determine the inter-relationship between platelets and inflammation-and especially IL-1β-in a cohort of healthy volunteers.

Methods:  We used data from the 500-Human Functional Genomics cohort, which consists of approximately 500 Caucasian, healthy individuals. We determined associations of plasma levels of IL-1β and other inflammatory proteins with platelet number and reactivity, the association of platelet reactivity with ex vivo cytokine production as well as the impact of genetic variations through a genome-wide association study (GWAS).

Results:  Platelets were associated with IL-1β on different levels. First, platelet number was positively associated with plasma IL-1β concentrations ( = 8.9 × 10) and inversely with concentrations of α-1-anti-trypsin ( = 1.04 × 10), which is a known antagonist of IL-1β. Second, platelet degranulation capacity, as determined by agonist-induced P-selectin expression, was associated with ex vivo IL-1β and IL-6 production. Third, several platelet single-nucleotide polymorphisms (SNPs) were associated with cytokine production and there was a significant platelet SNP enrichment in specific biological important pathways. Finally, platelet SNPs were enriched among SNPs earlier identified in GWAS studies in blood-related diseases and immune-mediated diseases.

Conclusion:  This comprehensive assessment of factors associated with platelet number and reactivity reinforces the important inter-relationship of platelets and IL-1β-mediated inflammation.
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http://dx.doi.org/10.1055/s-0038-1675603DOI Listing
December 2018

Host and Environmental Factors Influencing Individual Human Cytokine Responses.

Cell 2016 11;167(4):1111-1124.e13

Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Gelderland 6500HB, the Netherlands. Electronic address:

Differences in susceptibility to immune-mediated diseases are determined by variability in immune responses. In three studies within the Human Functional Genomics Project, we assessed the effect of environmental and non-genetic host factors of the genetic make-up of the host and of the intestinal microbiome on the cytokine responses in humans. We analyzed the association of these factors with circulating mediators and with six cytokines after stimulation with 19 bacterial, fungal, viral, and non-microbial metabolic stimuli in 534 healthy subjects. In this first study, we show a strong impact of non-genetic host factors (e.g., age and gender) on cytokine production and circulating mediators. Additionally, annual seasonality is found to be an important environmental factor influencing cytokine production. Alpha-1-antitrypsin concentrations partially mediate the seasonality of cytokine responses, whereas the effect of vitamin D levels is limited. The complete dataset has been made publicly available as a comprehensive resource for future studies. PAPERCLIP.
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http://dx.doi.org/10.1016/j.cell.2016.10.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787854PMC
November 2016

Soluble uric acid primes TLR-induced proinflammatory cytokine production by human primary cells via inhibition of IL-1Ra.

Ann Rheum Dis 2016 Apr 3;75(4):755-62. Epub 2015 Feb 3.

Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands Radboud Institute of Molecular Life Science (RIMLS), Radboud University Medical Center, Nijmegen, The Netherlands.

Objectives: The study of the proinflammatory role of uric acid has focused on the effects of its crystals of monosodium urate (MSU). However, little is known whether uric acid itself can directly have proinflammatory effects. In this study, we investigate the priming effects of uric acid exposure on the cytokine production of primary human cells upon stimulation with gout-related stimuli.

Methods: Peripheral blood mononuclear cells (PBMCs) were harvested from patients with gout and healthy volunteers. Cells were pretreated with or without uric acid in soluble form for 24 h and then stimulated for 24 h with toll-like receptor (TLR)2 or TLR4 ligands in the presence or absence of MSU crystals. Cytokine production was measured by ELISA; mRNA levels were assessed using qPCR.

Results: The production of interleukin (IL)-1β and IL-6 was higher in patients compared with controls and this correlated with serum urate levels. Proinflammatory cytokine production was significantly potentiated when cells from healthy subjects were pretreated with uric acid. Surprisingly, this was associated with a significant downregulation of the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra). This effect was specific to stimulation by uric acid and was exerted at the level of gene transcription. Epigenetic reprogramming at the level of histone methylation by uric acid was involved in this effect.

Conclusions: In this study we demonstrate a mechanism through which high concentrations of uric acid (up to 50 mg/dL) influence inflammatory responses by facilitating IL-1β production in PBMCs. We show that a mechanism for the amplification of IL-1β consists in the downregulation of IL-1Ra and that this effect could be exerted via epigenetic mechanisms such as histone methylation. Hyperuricaemia causes a shift in the IL-1β/IL-1Ra balance produced by PBMCs after exposure to MSU crystals and TLR-mediated stimuli, and this phenomenon is likely to reinforce the enhanced state of chronic inflammation.
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http://dx.doi.org/10.1136/annrheumdis-2014-206564DOI Listing
April 2016

Suppression of monosodium urate crystal-induced cytokine production by butyrate is mediated by the inhibition of class I histone deacetylases.

Ann Rheum Dis 2016 Mar 14;75(3):593-600. Epub 2015 Jan 14.

Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.

Objectives: Acute gouty arthritis is caused by endogenously formed monosodium urate (MSU) crystals, which are potent activators of the NLRP3 inflammasome. However, to induce the release of active interleukin (IL)-1β, an additional stimulus is needed. Saturated long-chain free fatty acids (FFAs) can provide such a signal and stimulate transcription of pro-IL-1β. In contrast, the short-chain fatty acid butyrate possesses anti-inflammatory effects. One of the mechanisms involved is inhibition of histone deacetylases (HDACs). Here, we explored the effects of butyrate on MSU+FFA-induced cytokine production and its inhibition of specific HDACs.

Methods: Freshly isolated peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with MSU and palmitic acid (C16.0) in the presence or absence of butyrate or a synthetic HDAC inhibitor. Cytokine responses were measured with ELISA and quantitative PCR. HDAC activity was measured with fluorimetric assays.

Results: Butyrate decreased C16.0+MSU-induced production of IL-1β, IL-6, IL-8 and IL-1β mRNA in PBMCs from healthy donors. Similar results were obtained in PBMCs isolated from patients with gout. Butyrate specifically inhibited class I HDACs. The HDAC inhibitor, panobinostat and the potent HDAC inhibitor, ITF-B, also decreased ex vivo C16.0+MSU-induced IL-1β production.

Conclusions: In agreement with the reported low inhibitory potency of butyrate, a high concentration was needed for cytokine suppression, whereas synthetic HDAC inhibitors showed potent anti-inflammatory effects at nanomolar concentrations. These novel HDAC inhibitors could be effective in the treatment of acute gout. Moreover, the use of specific HDAC inhibitors could even improve the efficacy and reduce any potential adverse effects.
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http://dx.doi.org/10.1136/annrheumdis-2014-206258DOI Listing
March 2016

High-density lipoprotein cholesterol subfractions HDL2 and HDL3 are reduced in women with rheumatoid arthritis and may augment the cardiovascular risk of women with RA: a cross-sectional study.

Arthritis Res Ther 2012 May 14;14(3):R116. Epub 2012 May 14.

Department of Rheumatology, Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, 6500 HB Nijmegen, The Netherlands.

Introduction: Higher levels of high density lipoprotein (HDL) subfractions HDL3-chol and particularly HDL2-chol protect against cardiovascular disease (CVD), but inflammation reduces the HDL level and may impair its anti-atherogenic effect. Changed HDL composition through the impact of inflammation on HDL subfractions may contribute to the excess risk of CVD in rheumatoid arthritis (RA). In this study, we investigated whether HDL2-chol and HDL3-chol concentrations differ between RA patients and healthy controls, and whether these levels are related to the level of RA disease activity.

Methods: Non-fasting blood samples were collected from 45 RA patients and 45 healthy controls. None of the participants had a history of CVD, diabetes, or used lipid-lowering drugs. HDL2-chol and HDL3-chol concentrations were obtained by ultracentrifugation. Regression modeling was used to compare HDL subfraction levels between RA patients and healthy controls, and to analyze the effect of disease activity on HDL2-chol and HDL3-chol.

Results: HDL2-chol and HDL3-chol were significantly lower in RA patients compared to healthy controls (P = 0.01, P = 0.005, respectively). The HDL2:HDL3 ratio was significantly lower in patients compared to controls (P = 0.04). Reduced HDL2-chol and HDL3-chol levels were primarily present in female RA patients and not in male RA patients. A modest effect of the disease activity score in 28 joins ( DAS28) on HDL2-chol concentrations was found, after correction for disease duration, glucocorticosteroid use and body mass index (BMI), with a 0.06 mmol/L decrease with every point increase in DAS28 (P = 0.05). DAS28 did not significantly affect HDL3-chol concentrations (P = 0.186).

Conclusions: Both HDL subfractions but particularly HDL2-chol concentrations were decreased in RA, primarily in women. This seems to be associated with disease activity and is of clinical relevance. The reduction of the HDL subfraction concentrations, particularly the supposedly beneficial HDL2-chol, may negatively impact the cardiovascular risk profile of women with RA.
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http://dx.doi.org/10.1186/ar3842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446493PMC
May 2012

Adiponectin multimer distribution in patients with familial combined hyperlipidemia.

Biochem Biophys Res Commun 2008 Nov 30;376(1):164-8. Epub 2008 Aug 30.

Department of General Internal Medicine 463, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

Adiponectin is secreted from adipocytes in different multimers, of which the high molecular weight (HMW) form is supposed to mediate favorable metabolic and anti-atherogenic effects. We determined adiponectin multimers in 29 female and 22 male patients with familial combined hyperlipidemia (FCH) and 51 age-, gender-, and BMI-matched controls in relation to cardiovascular disease (CVD). We observed a clear sexual dimorphism of total adiponectin and its multimers. Female, but not male, FCH patients had significant lower total adiponectin and both HMW and low molecular weight (LMW) adiponectin than controls. The adiponectin sensitivity index (ASI), reflected by HMW/total adiponectin, and the LMW/HMW adiponectin ratio did not differ significantly between FCH females and control females. However, FCH females with CVD exhibited significantly lower ASI (34.2+/-10.1% vs 46.0+/-7.1%) and higher LMW/HMW ratio (1.5+/-0.8 vs 0.7+/-0.3) compared to FCH females without CVD, reflecting a more atherogenic adiponectin multimer distribution.
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http://dx.doi.org/10.1016/j.bbrc.2008.08.111DOI Listing
November 2008

Circulating CXCL16 is not related to circulating oxLDL in patients with rheumatoid arthritis.

Biochem Biophys Res Commun 2007 Apr 6;355(2):392-7. Epub 2007 Feb 6.

Department of Rheumatology, Radboud University Nijmegen Medical Centre and Nijmegen Centre of Molecular Life Sciences, The Netherlands.

CXCL16 acts as a scavenger receptor for oxLDL in its membrane-bound form and induces migration of activated T cells in its soluble form. Due to these properties, CXCL16 has been suggested to play a role in both atherosclerosis and rheumatoid arthritis (RA). Our aim was to evaluate the contribution of soluble CXCL16 to the scavenging of oxLDL and its potential as a marker for cardiovascular disease (CVD) in patients with RA. We found that circulating CXCL16 was not correlated with plasma oxLDL or ApoB and was not related to the presence of CVD in RA patients. Moreover, CXCL16 did not bind and scavenge oxLDL in an in vitro setting. These data suggest that binding of oxLDL by soluble CXCL16 does not play a role in atherosclerosis and, although confirmation in larger studies is needed, that circulating CXCL16 is not related to the presence of CVD in patients with RA.
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http://dx.doi.org/10.1016/j.bbrc.2007.01.161DOI Listing
April 2007

Serum non-transferrin-bound iron and low-density lipoprotein oxidation in heterozygous hemochromatosis.

Biochem Biophys Res Commun 2006 Jun 2;345(1):371-6. Epub 2006 May 2.

Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Unlabelled: Non-transferrin-bound iron (NTBI) is implicated in lipid peroxidation but the relation with oxidative modification of low-density lipoprotein (LDL) is not known. We assessed variables reflecting in vitro and in vivo LDL oxidation in two age- and sex-matched groups (n=23) of hereditary hemochromatosis heterozygotes (C282Y), characterized by a clear difference in mean serum NTBI (1.55+/-0.57 micromol/L vs 3.70+/-0.96 micromol/L). Plasma level of oxidized LDL (absolute and relative to plasma apolipoprotein B), and IgG and IgM antibodies to oxidized LDL, markers of in vivo LDL oxidation, did not differ between the groups with low and high serum NTBI. Mean lag-phase of in vitro LDL oxidation was also not significantly different between both study groups.

Conclusion: these findings do not support the hypothesis that NTBI promotes oxidative modification of plasma LDL.
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http://dx.doi.org/10.1016/j.bbrc.2006.04.100DOI Listing
June 2006

Decreased adiponectin levels in familial combined hyperlipidemia patients contribute to the atherogenic lipid profile.

J Lipid Res 2005 Nov 16;46(11):2398-404. Epub 2005 Aug 16.

Department of Medicine and Division of General Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.

Familial combined hyperlipidemia (FCH) is characterized by increased levels of total cholesterol, triglycerides, and/or apolipoprotein B. Other features of FCH are obesity and insulin resistance. Adiponectin is a secretory product of the adipose tissue. Low levels of adiponectin are associated with insulin resistance and accelerated atherosclerosis. The aim of this study was to determine whether decreased adiponectin levels are associated with FCH and its phenotypes. The study population comprised 644 subjects, including 158 patients with FCH. Serum adiponectin levels were determined using a commercially available ELISA. For both males and females, the mean adiponectin level (microg/ml) was significantly lower in FCH patients [2.0 (1.8-2.2) and 2.5 (2.3-2.8), respectively] compared with normolipidemic relatives [2.3 (2.2-2.5) and 3.1 (2.8-3.3), respectively] and spouses [2.4 (2.1-2.7) and 3.2 (2.8-3.6), respectively]. These differences remain significant after adjusting for waist circumference and insulin resistance. Low adiponectin level in FCH patients was a superior independent predictor of the atherogenic lipid profile, including high triglyceride levels, low HDL-cholesterol levels, and the amount of small, dense LDL present, compared with both obesity and insulin resistance. Low adiponectin levels may contribute to the atherogenic lipid profile in FCH, independent of insulin resistance and obesity, as measured by waist circumference. This finding implies a role of adipose tissue metabolism in the pathophysiology of FCH.
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http://dx.doi.org/10.1194/jlr.M500212-JLR200DOI Listing
November 2005
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