Serum immunoglobulin G4 levels and Graves’ disease phenotype

Abstract

Purpose

We investigated, at diagnosis, the relationship between serum immunoglobulin G4 levels and the main characteristics of Graves' disease: hyperthyroidism severity, goiter size, presence of active Graves' ophthalmopathy, antithyroid antibodies status, and titer.

Methods

This prospective study included 80 newly diagnosed Graves' disease patients. The main parameters measured at diagnosis: thyroid-stimulating hormone, free thyroxine, free triiodothyronine, total triiodothyronine, thyroglobulin, antithyroid peroxidase antibodies, anti-thyroglobulin antibodies, thyroid-stimulating hormone receptor antibodies, immunoglobulin G4.

Results

In Graves' disease patients, serum immunoglobulin G4 levels were higher than in general population (p = 0.028) and higher in men compared to women (p = 0.002). Only one female patient with intense hypoechoic goiter, high anti-thyroglobulin antibody, and antithyroid peroxidase antibody titers had an elevated serum immunoglobulin G4 level at diagnosis. Patients with immunoglobulin G4 levels above the 75th percentile (>237.52 mg/dl, N = 20) were younger at Graves' ophthalmopathy onset (p < 0.001), had higher antithyroid peroxidase antibody (p = 0.01), and anti-thyroglobulin antibody levels (p = 0.006) and required shorter duration of the first methimazole treatment cycle (p = 0.041) than patients with immunoglobulin G4 below the 75th percentile. At diagnosis, patients with immunoglobulin G4 levels above the 90th percentile (>286.28 mg/dl, N = 8) had lower total triiodothyronine values (p = 0.001) than patients with IgG below the 90th percentile. No significant correlations were found between smoking status (p = 0.58), goiter size (p = 0.50), the presence of ophthalmopathy (p = 0.42) or thyroid-stimulating hormone receptor antibody titers (p = 0.45) and the mean value of immunoglobulin G4 levels at diagnosis.

Conclusions

Our data suggest that Graves' disease patients with elevated immunoglobulin G4 levels at diagnosis have a phenotype characterized by higher anti-thyroglobulin antibody and antithyroid peroxidase antibody titers, less severe T3 hyperthyroidism, younger age at ophthalmopathy onset and require a shorter duration of the first methimazole treatment cycle.

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Exploring attitudes towards endocrine diseases in Greece

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Does testicular anti-Müllerian hormone extend life?

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The influence of phthalates and bisphenol A on the obesity development and glucose metabolism disorders

Abstract

The prevalence of obesity and type 2 diabetes mellitus epidemics presents a great health problem worldwide. Beside the changes in diet and decreased physical activity, there is growing interest in endocrine disrupting chemicals that may have effects on these conditions. Among them, the role of certain phthalates and bisphenol A is confirmed. We have summarized the existing literature on this issue including cross-sectional, follow up epidemiological studies and in vivo and in vitro studies. Most data support the effects of bisphenol A and some phthalates, such as di-2-ethyl-hexyl phthalate, diethyl phthalate, dibuthyl phthalate, dimethyl phthalate, dibenzyl phthalate, diisononyl phthalate and others on the development obesity and type 2 diabetes mellitus. These endocrine disrupting chemicals interfere with different cell signaling pathways involved in weight and glucose homeostasis. Since the data are rather inconsistent, there is a need for new, well-designed prospective studies.

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Weighing the Evidence: Bias and Confounding in Epidemiologic Studies in Allergy/Immunology

Publication date: Available online 7 November 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Elizabeth C. Matsui, Corinne A. Keet




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Endogenous polyclonal anti-IL-1 antibody responses potentiate IL-1 activity during pathogenic inflammation

Publication date: Available online 7 November 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Gunther Spohn, Natalia Arenas-Ramirez, Gregory Bouchaud, Onur Boyman
BackgroundParticular neutralizing monoclonal antibodies to certain cytokines act as agonists in vivo by protection of the cytokine's active site and prolongation of cytokine half-life. While this principle might be useful for targeted immunotherapy, its role in the pathogenesis of inflammation and autoimmunity is unclear.ObjectiveWe sought to determine whether slight, structurally non-relevant modifications of the prototypic pro-inflammatory cytokine interleukin-1β (IL-1β) during an immune response could elicit polyclonal anti-IL-1β antibody responses that modulated IL-1β's in vivo activity.MethodsWe engineered two different IL-1β variants, thereby mimicking the process of cytokine modification occurring during inflammation, and conjugated them to virus-like particles, followed by immunization of mice. The resulting polyclonal anti-IL-1β antibody responses were assessed using in vitro and in vivo assays as well as two relevant (auto-) inflammatory murine models.ResultsWhile antibody responses generated to one variant were potently inhibiting IL-1β, antibody responses induced by the other variant even potentiated the in vivo effects of IL-1β; the latter led to enhanced morbidity in two different IL-1β-mediated mouse models, including a model of inflammatory bowel disease and an inflammatory arthritis model.ConclusionThese data demonstrate that endogenous polyclonal anti-cytokine antibody responses can enhance the cytokine's activity in inflammatory and autoimmune diseases.

Teaser

Capsule summary: Polyclonal anti-cytokine autoantibodies, endogenously generated during an anti-virus-like immune response, can boost, rather than neutralize, pro-inflammatory cytokines thus exacerbating (auto-) inflammatory disorders.


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Precision combination therapy for triple negative breast cancer via biomimetic polydopamine polymer core-shell nanostructures

Publication date: January 2017
Source:Biomaterials, Volume 113
Author(s): Yanping Ding, Shishuai Su, Ruirui Zhang, Leihou Shao, Yinlong Zhang, Bin Wang, Yiye Li, Long Chen, Qun Yu, Yan Wu, Guangjun Nie
Photothermal-based combination therapy using functional nanomaterials shows great promise in eradication of aggressive tumors and improvement of drug sensitivity. The therapeutic efficacy and adverse effects of drug combinations depend on the precise control of timely tumor-localized drug release. Here a polymer-dopamine nanocomposite is designed for combination therapy, thermo-responsive drug release and prevention of uncontrolled drug leakage. The thermo-sensitive co-polymer poly (2-(2-methoxyethoxy) ethyl methacrylate-co-oligo (ethylene glycol) methacrylate)-co-2-(dimethylamino) ethyl methacrylate-b-poly (D, l-lactide-co-glycolide) is constructed into core-shell structured nanoparticles for co-encapsulation of two cytotoxic drugs and absorption of small interfering RNAs against survivin. The drug-loaded nanoparticles are surface-coated with polydopamine which confers the nanoformulation with photothermal activity and protects drugs from burst release. Under tumor-localized laser irradiation, polydopamine generates sufficient heat, resulting in nanoparticle collapse and instant drug release within the tumor. The combination strategy of photothermal, chemo-, and gene therapy leads to triple-negative breast cancer regression, with a decrease in the chemotherapeutic drug dosage to about 1/20 of conventional dose. This study establishes a powerful nanoplatform for precisely controlled combination therapy, with dramatic improvement of therapeutic efficacy and negligible side effects.



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