Dataset Information

Evaluating the Role of Circulating Dendritic Cells in Methimazole-Treated Pediatric Graves' Disease Patients.

ABSTRACT: Graves' disease (GD) is hyperthyroidism associated with organ-specific autoimmune inflammation. GD occurs more frequently in adults than in children; however, pediatric patients are a therapeutic challenge due to cycles of remissions and relapses requiring constant monitoring at every stage of treatment administered. Dendritic cells (DCs) are considered to be a link between innate and adaptive immunity. DCs, as antigen-presenting cells (APCs), are involved in antigen presentation to T lymphocytes, thereby initiating a shift towards effector cells. In accordance, DCs also participate in the modulation of tolerance to specific antigens. To date, the data on DCs' role in Graves' pathological processes are scarce. Therefore, here, we evaluated the frequencies and role of circulating DCs in GD pediatric patients treated with methimazole. Flow cytometric analysis was implemented to evaluate three subsets of dendritic cells and their correlation with clinical GD-related parameters. We found significantly higher levels of DC subsets in patients at diagnosis. Furthermore, methimazole treatment seemed to effectively reduce subsets of DCs, which, in addition, were found to differentially correlate with thyroid function. Our study shed new light on DCs' role in the pediatric GD pathomechanism. Further studies are required for the mechanistic assessment of DCs' exact role in disease progression and influence on thyroid function.

SUBMITTER: Starosz A

PROVIDER: S-EPMC7911035 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Evaluating the Role of Circulating Dendritic Cells in Methimazole-Treated Pediatric Graves' Disease Patients.

Starosz Aleksandra A Stożek Karolina K Moniuszko Marcin M Grubczak Kamil K Bossowski Artur A

Genes 20210126 2

Graves' disease (GD) is hyperthyroidism associated with organ-specific autoimmune inflammation. GD occurs more frequently in adults than in children; however, pediatric patients are a therapeutic challenge due to cycles of remissions and relapses requiring constant monitoring at every stage of treatment administered. Dendritic cells (DCs) are considered to be a link between innate and adaptive immunity. DCs, as antigen-presenting cells (APCs), are involved in antigen presentation to T lymphocyte ...[more]

PMID: 33530368

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Project description:IntroductionMethimazole (MMI) represents the conventional therapeutic agent for Graves' disease (GD) hyperthyroidism, but MMI efficacy is limited since it marginally affects the underlying autoimmune process. In a previous study, we randomly assigned 42 newly diagnosed GD patients with insufficient vitamin D (VitD) and selenium (Se) levels to treatment with MMI alone (standard) or combined with selenomethionine and cholecalciferol (intervention) and observed a prompter resolution of hyperthyroidism in the intervention group.MethodsIn the present study, we aimed to explore changes in peripheral T regulatory (Treg) and circulating natural killer (NK) cell frequency, circulating NK cell subset distribution and function, during treatment.ResultsAt baseline, circulating total CD3-CD56+NK cells and CD56bright NK cells were significantly higher in GD patients than in healthy controls (HC) (15.7 ± 9.6% vs 9.9 ± 5.6%, p=0.001; 12.2 ± 10.3% vs 7.3 ± 4.1%, p=0.02, respectively); no differences emerged in Treg cell frequency. Frequencies of total NK cells and CD56bright NK cells expressing the activation marker CD69 were significantly higher in GD patients than in HC, while total NK cells and CD56dim NK cells expressing CD161 (inhibitory receptor) were significantly lower. When co-cultured with the K562 target cell, NK cells from GD patients had a significantly lower degranulation ability compared to HC (p<0.001). Following 6 months of treatment, NK cells decreased in both the intervention and MMI-alone groups, but significantly more in the intervention group (total NK: -10.3%, CI 95% -15.8; -4.8% vs -3.6%, CI 95% -9; 1.8%, p=0.09 and CD56bright NK cells: -6.5%, CI 95% -10.1; -3 vs -0.9%, CI 95% -4.4; 2%, p=0.03). Compared to baseline, CD69+ NK cells significantly decreased, while degranulation ability slightly improved, although no differences emerged between the two treatment groups. Compared to baseline, Treg cell frequency increased exclusively in the intervention group (+1.1%, CI 95% 0.4; 1.7%).DiscussionThis pilot study suggested that VitD and Se supplementation, in GD patients receiving MMI treatment, modulates Treg and NK cell frequency, favoring a more pronounced reduction of NK cells and the increase of Treg cells, compared to MMI alone. Even if further studies are needed, it is possible to speculate that this immunomodulatory action might have facilitated the prompter and better control of hyperthyroidism in the supplemented group observed in the previous study.

Project description:BackgroundHyperthyroidism is related to vascular atherosclerosis. Propylthiouracil (PTU) and methimazole, other than their antithyroid effects, may have different mechanisms in preventing atherogenesis in Graves' disease.ObjectiveThis study aimed to investigate the effect of antithyroid drugs on markers of vascular atherosclerosis in Graves' hyperthyroidism.MethodsThis study was a single-blind, randomized clinical trial conducted on 36 patients with Graves' disease in Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, from June 2019 until July 2020. Graves' disease was diagnosed from clinical manifestation of hyperthyroidism with diffuse goiter and then confirmed by thyroid stimulation hormone (TSH), free T4 (fT4), and TSH-receptor antibody (TRAb) measurements. Participants were randomly assigned to either a PTU or a methimazole treatment group and followed up for 3 months. Markers of vascular atherosclerosis were represented by adhesion molecules [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin], carotid artery stiffness [pulse wave velocity (PWV)], and thickness [carotid intima media thickness (cIMT)].ResultsBy the end of the study, 24 participants reached euthyroid condition (13 from the PTU group and 11 from the methimazole group). After 3 months of follow-up, in the PTU group, we noticed an improvement of ICAM-1 [pretreatment: 204.1 (61.3) vs. posttreatment: 141.6 (58.4) ng/ml; p = 0.001], VCAM-1 [837 (707-977) vs. 510 (402-630) ng/ml; p < 0.001] and E-selectin [32.1 (24.1-42.7) vs. 28.2 (21.6-36.8) ng/ml; p = 0.045] in the PTU group. In the methimazole group, only VCAM-1 improvement [725 (565-904) vs. 472 (367-590); p = 0.001] was observed. Meanwhile, we found no significant changes in PWV or cIMT in either group.ConclusionAntithyroid treatment in Graves' disease leads to improvement in adhesion molecules, with a lesser effect on methimazole, whereas there were no significant changes in PWV or cIMT. PTU may have a better mechanism compared with methimazole in terms of improving adhesion molecules.

Project description:Prompt and stable control of hyperthyroidism is fundamental to avoid the detrimental effects of thyroid hormone excess, and antithyroid drugs, mainly methimazole (MMI), represent the first-line treatment for Graves' disease (GD) hyperthyroidism. Decreased serum concentrations of selenium (Se) and calcifediol (25(OH)D, VitD) have been reported in newly diagnosed GD patients in observational studies. Low Se levels might exacerbate oxidative stress by compromising the antioxidant machinery's response to reactive oxygen species, and low VitD levels might hamper the anti-inflammatory immune response. We performed a randomized controlled clinical trial (EudraCT 2017-00505011) to investigate whether Se and cholecalciferol (VitD) addition to MMI is associated with a prompter control of hyperthyroidism. Forty-two consecutive patients with newly-onset GD and marginal/insufficient Se and VitD levels were randomly assigned to treatment with either MMI monotherapy or MMI combined with Se and VitD. Se treatment was withdrawn after 180 days, while the other treatments were continued. Combination therapy resulted in a significantly greater reduction in serum FT4 concentration at 45 days (-37.9 pg/ml, CI 95%, -43.7 to -32.2 pg/ml) and 180 days (-36.5 pg/ml, CI 95%, -42 to -30.9 pg/ml) compared to MMI monotherapy (respectively: -25.7 pg/ml, CI 95%, -31.6 to -19.7 pg/ml and -22.9 pg/ml, CI 95%, -28 to -17.3 pg/ml, p 0.002). Data at 270 days confirmed this trend (-37.8 pg/ml, CI 95%, -43.6 to -32.1 pg/ml vs -24.4 pg/ml, CI 95%, -30.3 to -18.4 pg/ml). The quality of life (QoL) score was investigated by the validated "Thyroid-related Patient-Reported Outcome" questionnaire (ThyPRO). ThyPRO composite score showed a greater improvement in the intervention group at 45 days (-14.6, CI 95%, -18.8 to -10.4), 180 (-9, CI 95%, -13.9 to -4.2) and 270 days (-14.3, CI 95%, -19.5 to -9.1) compared to MMI group (respectively, -5.2, CI 95%, -9.5 to -1; -5.4, CI 95%, -10.6 to -0.2 and -3.5, CI 95%, -9 to -2.1, p 0-6 months and 6-9 months <0.05). Our results suggest that reaching optimal Se and VitD levels increases the early efficacy of MMI treatment when Se and VitD levels are suboptimal.

Dataset Information

Evaluating the Role of Circulating Dendritic Cells in Methimazole-Treated Pediatric Graves' Disease Patients.

Publications

Evaluating the Role of Circulating Dendritic Cells in Methimazole-Treated Pediatric Graves' Disease Patients.

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