Changes in Serum Adhesion Molecules, Chemokines, Cytokines, and Tissue Remodeling Factors in Euthyroid Women Without Thyroid Antibodies Who Are at Risk for Autoimmune Thyroid Disease: A Hypothesis on the Early Phases of the Endocrine Autoimmune Reaction

Beumer, Wouter; Effraimidis, Grigoris; Drexhage, Roosmarijn C.; Wiersinga, Wilmar M.; Drexhage, Hemmo A.

doi:10.1210/jc.2012-4122

Cited by 15 publications

(16 citation statements)

References 39 publications

(44 reference statements)

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“…But at this stage in subjects at risk to develop AITD (like those with a family history of AITD), evidence of immune activation can already be found from a characteristic pattern of serum proteins related to growth/connective tissue abnormalities and migration/accumulation abnormalities of macrophages and dendritic cells (95). In stage II, thyroid antibodies become detectable in serum.…”

Section: Drugsmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Autoimmune thyroid disease: old and new players

Effraimidis

Wiersinga

2014

European Journal of Endocrinology

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284

196

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The last 10 years have seen some progress in understanding the etiology of autoimmune thyroid disease (AITD). The female preponderance can now be explained -at least in part -by fetal microchimerism and X-chromosome inactivation. The number of identified susceptibility genes for AITD is increasing (among others now including TSHR, TG, HLA, CTLA4, PTPN22, CD40, FCRL3, IL2RA, and FOXP3), but these genes together probably do not explain more than about 10% of the heritability of AITD. As twin studies indicate that genes contribute for 70% of AITD, it follows that there must be many more loci, each of them contributing a little. While the genetic studies have clarified why various autoimmune diseases so often cluster in the same patient, the molecular mechanism of action of these genetic polymorphisms (frequently located in introns) has hardly been explained. Polymorphisms in AITD susceptibility genes may become helpful in clinical practice, e.g. in assessing risk of recurrent Graves' hyperthyroidism (GH) after a course of antithyroid drugs. Moderate alcohol intake decreases the risk on overt GH and overt Hashimoto's hypothyroidism. Current smokers -as well known -are at increased risk for Graves' disease, but -surprisingly -at diminished risk for Hashimoto's thyroiditis. Low selenium and low vitamin D levels might increase the risk of developing AITD, but data are still inconclusive. Current options for preventive interventions in subjects at risk to develop AITD are very limited.

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Section: Drugsmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Autoimmune thyroid disease: old and new players

Effraimidis

Wiersinga

2014

European Journal of Endocrinology

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284

196

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“…A role for other growth factors in the pathogenesis of mood disorders has also been suggested, including a role for PDGF, which has been shown to be altered in the serum of psychiatric patients [34]. We have reported on abnormal serum levels of BDNF and PDGF in patients prone to mood disorders and thyroid autoimmunity [35,36]. …”

Section: Introductionmentioning

confidence: 99%

Exaggerated Increases in Microglia Proliferation, Brain Inflammatory Response and Sickness Behaviour upon Lipopolysaccharide Stimulation in Non-Obese Diabetic Mice

McGuiness

Gibney

Beumer

et al. 2016

Neuroimmunomodulation

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The non-obese diabetic (NOD) mouse, an established model for autoimmune diabetes, shows an exaggerated reaction of pancreas macrophages to inflammatory stimuli. NOD mice also display anxiety when immune-stimulated. Chronic mild brain inflammation and a pro-inflammatory microglial activation is critical in psychiatric behaviour. Objective: To explore brain/microglial activation and behaviour in NOD mice at steady state and after systemic lipopolysaccharide (LPS) injection. Methods: Affymetrix analysis on purified microglia of pre-diabetic NOD mice (8-10 weeks) and control mice (C57BL/6 and CD1 mice, the parental non-autoimmune strain) at steady state and after systemic LPS (100 μg/kg) administration. Quantitative PCR was performed on the hypothalamus for immune activation markers (IL-1β, IFNγ and TNFα) and growth factors (BDNF and PDGF). Behavioural profiling of NOD, CD1, BALB/c and C57BL/6 mice at steady state was conducted and sickness behaviour/anxiety in NOD and CD1 mice was monitored before and after LPS injection. Results: Genome analysis revealed cell cycle/cell death and survival aberrancies of NOD microglia, substantiated as higher proliferation on BrdU staining. Inflammation signs were absent. NOD mice had a hyper-reactive response to novel environments with some signs of anxiety. LPS injection induced a higher expression of microglial activation markers, a higher brain pro-inflammatory set point (IFNγ, IDO) and a reduced expression of BDNF and PDGF after immune stimulation in NOD mice. NOD mice displayed exaggerated and prolonged sickness behaviour after LPS administration. Conclusion: After stimulation with LPS, NOD mice display an increased microglial proliferation and an exaggerated inflammatory brain response with reduced BDNF and PDGF expression and increased sickness behaviour as compared to controls.

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“…Our analysis of the serum chemokine levels in the ALA, AC, and E. dispar groups revealed several interesting aspects. First, the three groups had equivalently high levels of CCL2, but high serum levels of CCL2 had also been shown in other healthy control groups [ 45 ],[ 46 ]. Second, sex analyses revealed that the male AC subjects had significantly higher CCL2 levels than female AC.…”

Section: Discussionmentioning

confidence: 76%

Immune markers characteristic for asymptomatically infected and diseased Entamoeba histolytica individuals and their relation to sex

et al. 2014

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BackgroundThe protozoan parasite Entamoeba histolytica (E. histolytica) usually asymptomatically colonizes the human intestine. In the minority of the cases, the parasite evades from the gut and can induce severe symptoms like colitis or amebic liver abscess (ALA). Interestingly, ALA predominates in adult men despite a higher prevalence of the parasite in women. The present study aimed to identify characteristic serum markers in a unique cohort of clearly defined asymptomatically infected E. histolytica individuals in comparison to patients with an E. histolytica liver manifestation of both sex.MethodsThe following study groups were investigated: ALA patients (n = 38), healthy asymptomatic E. histolytica carriers (AC) (n = 44), and healthy E. dispar-infected controls (n = 24) out of an amebiasis endemic area. E. histolytica-specific immunoglobulin G (IgG) and the IgG subclasses against proteinaceous and non-proteinaceous amebic antigens were measured by ELISA. Serum cytokine and chemokine levels were investigated using a flow cytometry bead-based multiplex immunoassay.ResultsThe IgG results revealed that not only ALA patients, but also AC, developed high E. histolytica-specific titers of IgG and all IgG subclasses as well as IgA. IgG and IgG2 titers against the glycolipid E. histolytica lipophosphoglycan were highest in ALA patients. As in ALA patients, high cytokine levels of interleukin (IL-) 4 were detected in AC compared to E. dispar infected individuals, while IL-6 was exclusively elevated in ALA patients. IL-10 was lower in AC compared to ALA patients. Equal serum levels of CCL2 were found in all study groups but ALA patients showed decreased levels of CCL3. Sex dependent analysis of the data indicated significantly higher IgG and IgG1 titers in female AC compared to male AC. CCL2, the chemokine involved in immunopathology in the mouse model for the disease, was higher in male AC compared to female AC.ConclusionIn this study we characterize for the first time an asymptomatic carrier stage in amebiasis that is associated with a significant immune reaction and provide immunological markers that might give first hints towards an understanding of immune mechanisms underlying the control or development of invasive amebiasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0621-1) contains supplementary material, which is available to authorized users.

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Changes in Serum Adhesion Molecules, Chemokines, Cytokines, and Tissue Remodeling Factors in Euthyroid Women Without Thyroid Antibodies Who Are at Risk for Autoimmune Thyroid Disease: A Hypothesis on the Early Phases of the Endocrine Autoimmune Reaction

Cited by 15 publications

References 39 publications

MECHANISMS IN ENDOCRINOLOGY: Autoimmune thyroid disease: old and new players

MECHANISMS IN ENDOCRINOLOGY: Autoimmune thyroid disease: old and new players

Exaggerated Increases in Microglia Proliferation, Brain Inflammatory Response and Sickness Behaviour upon Lipopolysaccharide Stimulation in Non-Obese Diabetic Mice

Immune markers characteristic for asymptomatically infected and diseased Entamoeba histolytica individuals and their relation to sex

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