Cellular and molecular basis of thyroid autoimmunity

Bogusławska, Joanna; Godlewska, Marlena; Gajda, Ewa; Piekiełko-Witkowska, Agnieszka

doi:10.1530/etj-21-0024

Cited by 65 publications

(67 citation statements)

References 63 publications

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“…However, this group had a more severe condition, thus, achieving mean TRAb levels similar to those of the MMI group, might supports the favorable impact of the supplementation. It should be recalled that TRAb synthesis is the culmination of a multi-step pathogenetic process that includes innate and cellular immunity in addition to the humoral counterpart ( 38 , 39 ). The combined treatment may have a stronger effect on cellular and innate immunity than on humoral immunity.…”

Section: Discussionmentioning

confidence: 99%

Add-On Effect of Selenium and Vitamin D Combined Supplementation in Early Control of Graves’ Disease Hyperthyroidism During Methimazole Treatment

et al. 2022

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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 Se treatment was withdrawn after 180 days, while the other treatments were continued.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.

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Section: Discussionmentioning

confidence: 99%

Add-On Effect of Selenium and Vitamin D Combined Supplementation in Early Control of Graves’ Disease Hyperthyroidism During Methimazole Treatment

et al. 2022

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“…The pathogenesis of post-HSCT autoimmunity is believed to be multifactorial, involving genetic, infectious, hormonal, and other environmental factors [ 29 ]. Many variants of genes involved in immune responses (e.g., HLA, PTPN22 , CTLA4 , and IL2RA ), thyroid function (e.g., TSHR , FOXE1 ), and other processes (e.g., LPP , TRIB2 ) have been linked to autoimmune thyroid dysfunctions [ 3 ]. A large single-center study focused on post-HSCT thyroid autoimmunity, including Graves’ disease and Hashimoto thyroiditis, reported a 2.9% 5-year actuarial rate for autoimmune thyroid dysfunction post-allogeneic HSCT [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Genetic predisposition and nongenetic factors have been linked to Graves’ disease, resulting in overproduction of thyroid hormones by thyroid epithelial cells due to overactive thyrotropin receptor. Together with drastically amplified intrathyroidal cytokine production by infiltrating immune cells, thyrotropin receptor overactivity further activates and sustains inflammation to alter the behavior of thyroid epithelial cells [ 2 , 3 , 4 ]. Allogeneic hematopoietic stem cell transplantation (HSCT) procedures, including cytoreductive therapies to condition and modulate graft–host interactions, represent artificial platforms for immune reconstitution and tolerance induction.…”

Section: Introductionmentioning

confidence: 99%

Evolution of Graves’ Disease during Immune Reconstitution following Nonmyeloablative Haploidentical Peripheral Blood Stem Cell Transplantation in a Boy Carrying Germline SAMD9L and FLT3 Variants

Fang

Shen

et al. 2022

IJMS

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Graves’ disease, characterized by hyperthyroidism resulting from loss of immune tolerance to thyroid autoantigens, may be attributable to both genetic and environmental factors. Allogeneic hematopoietic stem cell transplantation (HSCT) represents a means to induce immunotolerance via an artificial immune environment. We present a male patient with severe aplastic anemia arising from a germline SAMD9L missense mutation who successfully underwent HSCT from his HLA-haploidentical SAMD9L non-mutated father together with nonmyeloablative conditioning and post-transplant cyclophosphamide at 8 years of age. He did not suffer graft-versus-host disease, but Graves’ disease evolved 10 months post-transplant when cyclosporine was discontinued for one month. Reconstitution of peripheral lymphocyte subsets was found to be transiently downregulated shortly after Graves’ disease onset but recovered upon antithyroid treatment. Our investigation revealed the presence of genetic factors associated with Graves’ disease, including HLA-B*46:01 and HLA-DRB1*09:01 haplotypes carried by the asymptomatic donor and germline FLT3 c.2500C>T mutation carried by both the patient and the donor. Given his current euthyroid state with normal hematopoiesis, the patient has returned to normal school life. This rare event of Graves’ disease in a young boy arising from special HSCT circumstances indicates that both the genetic background and the HSCT environment can prompt the evolution of Graves’ disease.

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“…The mechanisms that lead to this loss of tolerance result from a complex interplay of environmental factors and genetic/epigenetic susceptibility. Recently, the microbiome has also been implicated 7…”

Section: Why Do People Develop Gd?mentioning

confidence: 99%

Graves’ disease: moving forwards

2022

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Graves’ disease is a rare disorder that continues to present clinicians and families with a series of challenges. There are no new established treatments for children or adolescents, but the outcomes of recent clinical trials and meta-analyses have helped clinicians to prepare families for the road ahead. We have a more refined understanding of how to administer antithyroid drugs, which one to use and how long to treat the young person. We also have a greater insight into how best to reduce any risks associated with surgery and radioiodine. We understand more about long-term outcomes and their determinants and have greater awareness about the impact of the disease and its treatment on quality of life. A holistic approach to management is key to supporting and counselling young people and their families about the diagnosis and management options. In this review, we will discuss the recent literature and reflect on how this should be translated into clinical practice.

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Cellular and molecular basis of thyroid autoimmunity

Cited by 65 publications

References 63 publications

Add-On Effect of Selenium and Vitamin D Combined Supplementation in Early Control of Graves’ Disease Hyperthyroidism During Methimazole Treatment

Add-On Effect of Selenium and Vitamin D Combined Supplementation in Early Control of Graves’ Disease Hyperthyroidism During Methimazole Treatment

Evolution of Graves’ Disease during Immune Reconstitution following Nonmyeloablative Haploidentical Peripheral Blood Stem Cell Transplantation in a Boy Carrying Germline SAMD9L and FLT3 Variants

Graves’ disease: moving forwards

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