Endocrinology and Metabolism

Original Articles

Thyroid
Programmed Cell Death-Ligand 1 (PD-L1) gene Single Nucleotide Polymorphism in Graves’ Disease and Hashimoto’s Thyroiditis in Korean Patients: Jee Hee Yoon, Min-ho Shin, Hee Nam Kim, Wonsuk Choi, Ji Yong Park, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang; Endocrinol Metab. 2021;36(3):599-606. Published online June 2, 2021; DOI: https://doi.org/10.3803/EnM.2021.965

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Background
Programmed cell death-ligand 1 (PD-L1) has an important role in regulating immune reactions by binding to programmed death 1 (PD-1) on immune cells, which could prevent the exacerbation of autoimmune thyroid disease (AITD). The aim of this study was to evaluate the association of PD-L1 polymorphism with AITD, including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT).
Methods
A total of 189 GD patients, 234 HT patients, and 846 healthy age- and sex-matched controls were enrolled in this study. We analyzed PD-L1 single nucleotide polymorphism (SNP) (rs822339) and investigated the associations with clinical disease course and outcome.
Results
Genotype frequency at the PD-L1 marker RS822339 in GD (P=0.219) and HT (P=0.764) patients did not differ from that among healthy controls. In patients with GD, the A/G or G/G genotype group demonstrated higher TBII titer (20.6±20.5 vs. 28.0± 25.8, P=0.044) and longer treatment duration (39.0±40.4 months vs. 62.4±65.0 months, P=0.003) compared to the A/A genotype group. Among patients in whom anti-thyroid peroxidase (TPO) antibody was measured after treatment of GD, post-treatment antiTPO positivity was higher in the A/G or G/G genotype group compared to the A/A genotype group (48.1% vs. 69.9%, P=0.045). Among patients with HT, there was no significant difference of anti-TPO antibody positivity (79.4% vs. 68.6%, P=0.121), anti-thyroglobulin antibody positivity (80.9% vs. 84.7%, P=0.661), or development to overt hypothyroidism (68.0% vs. 71.1%, P=0.632) between the A/A genotype group and the A/G or G/G genotype group.
Conclusion
The genotype frequency of PD-L1 (rs822339) is not different in patients with AITD compared with healthy controls. The intact PD-1/PD-L1 pathway in GD and HT might be important to maintain chronicity of AITD by protecting immune tolerance. However, the PD-L1 SNP could be associated with difficulty in achieving remission in patients with GD, which may be helpful to predict the possibility of longer treatment. Further studies are required to investigate the complex immune tolerance system in patients with AITD.

Citations

Citations to this article as recorded by

Synergistic effects of BTN3A1, SHP2, CD274, and STAT3 gene polymorphisms on the risk of systemic lupus erythematosus: a multifactorial dimensional reduction analysis
Yang-Yang Tang, Wang-Dong Xu, Lu Fu, Xiao-Yan Liu, An-Fang Huang
Clinical Rheumatology.2024; 43(1): 489. CrossRef
Relationship between CD274 gene polymorphism and systemic lupus erythematosus risk in a Chinese Han population
Lu‐Qi Yang, Zhen Qin, Lu Fu, Wang‐Dong Xu
International Journal of Rheumatic Diseases.2024;[Epub] CrossRef

Clinical Study
Characteristics of Immune-Related Thyroid Adverse Events in Patients Treated with PD-1/PD-L1 Inhibitors: Jee Hee Yoon, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang; Endocrinol Metab. 2021;36(2):413-423. Published online April 6, 2021; DOI: https://doi.org/10.3803/EnM.2020.906

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Background
Thyroid immune-related adverse events (IRAEs) have been reported in patients treated with programmed cell death protein-1 (PD-1) and programmed cell death protein-ligand 1 (PD-L1) inhibitors. We investigated the incidence and clinical course of PD-1/PD-L1 inhibitor-induced thyroid IRAEs, and identified predictable clinical risk factors of thyroid IRAEs, in particular, overt hypothyroidism (OH).
Methods
We retrospectively reviewed the medical records of 325 cancer patients receiving PD-1/PD-L1 inhibitor in a tertiary referral center.
Results
A total of 50.5% (164/325) of patients experienced at least one abnormal thyroid function following PD-1/PD-L1 inhibitor. Eighty-four patients (51.2%) of them recovered to normal thyroid function during follow-up. In overall population, 25 patients (7.7%) required thyroid hormone replacement therapy due to PD-1/PD-L1 inhibitor-induced OH. Patients who progressed to OH showed significantly higher baseline thyroid stimulating hormone level and longer duration of PD-1/PD-L1 inhibitor therapy than those without thyroid dysfunction or OH (both P<0.001). Median time interval to the development of OH was 3 months after the therapy. OH was significantly associated with positive anti-thyroid peroxidase antibody at baseline and anti-thyroglobulin antibody during the therapy than those without thyroid dysfunction or OH (P=0.015 and P=0.005, respectively). We observed no patients with OH who were able to stop levothyroxine replacement after the cessation of PD-1/PD-L1 inhibitor therapy.
Conclusion
PD-1/PD-L1 inhibitor-induced thyroid dysfunctions are considerably reversible; however, OH is irreversible requiring levothyroxine replacement even after stopping the therapy. Positive thyroid autoantibodies may predict the progression to OH.

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Review Article

Thyroid
Natural Killer Cells and Thyroid Diseases: Eun Kyung Lee, John B. Sunwoo; Endocrinol Metab. 2019;34(2):132-137. Published online June 24, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.2.132

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Abnormal production of thyroid hormone is one of the common endocrine disorders, and thyroid hormone production declines with age. The aging process also negatively affects the immune system. An interaction between endocrine system and the immune system has been proposed to be bidirectional. Emerging evidence suggests an interaction between a lymphocyte population, called natural killer (NK) cells and thyroid gland function. Here, we review the relationship between NK cells and thyroid function and disease.

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European Journal of Inflammation.2020; 18: 205873922094233. CrossRef
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Daniela Gallo, Eliana Piantanida, Matteo Gallazzi, Luigi Bartalena, Maria Laura Tanda, Antonino Bruno, Lorenzo Mortara
Frontiers in Endocrinology.2020;[Epub] CrossRef
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Frontiers in Endocrinology.2020;[Epub] CrossRef
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International Journal of Molecular Sciences.2019; 20(18): 4413. CrossRef

Original Article

Functional Role of Parkin against Oxidative Stress in Neural Cells: Minyoung Hwang, Ja-Myong Lee, Younghwa Kim, Dongho Geum; Endocrinol Metab. 2014;29(1):62-69. Published online March 14, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.1.62

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Background

Parkinson disease (PD) is caused by selective cell death of dopaminergic neurons in the substantia nigra. An early onset form of PD, autosomal recessive juvenile parkinsonism has been associated with a mutation in the parkin gene. The function of parkin is known to remove misfolding proteins and protect cell death. We aimed to investigate the role of parkin against oxidative stress in neuronal cells.

Methods

Parkin knockout embryonic stem cells (PKO ES cells) were differentiated into neurons by adherent monolayer culture method. Oxidative stress was induced by the treatment of 1-methyl-4-phenylpyridinium (MPP⁺) in neurons derived from wild type and PKO ES cells, and cell viability was examined by MTT assay. After exposure to MPP⁺, Tuj1-positive cell population was compared between PKO and wild type cells by fluorescence activated cell sorter (FACS) analysis. The activated caspase3 protein level was also measured by Western blot analysis, FACS and immunocytochemistry.

Results

There was no difference in the efficiency of neuronal differentiation between wild type and PKO ES cells. After exposure to MPP⁺, no significant differences were found in cell viability and Tuj1-positive cell population between the two groups determined by MTT assay and FACS analysis, respectively. The activated caspase3 protein levels examined by Western blot analysis, FACS and immunocytochemistry were not changed in PKO cells compared with those of wild type cells after MPP⁺ treatment.

Conclusion

These results suggest that PKO neuronal cells including dopaminergic neurons are not sensitive to caspase3-dependent cell death pathway during the response against MPP⁺-induced oxidative stress.

Citations

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Journal of Biomaterials and Tissue Engineering.2023; 13(10): 1017. CrossRef
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Nianping Zhang, Ying Lyu, Xuebing Pan, Liping Xu, Aiguo Xuan, Xiaosong He, Wandan Huang, Dahong Long
International Journal of Molecular Medicine.2017; 40(3): 814. CrossRef
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Articles in 'Endocrinology and Metabolism' in 2014
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Cellular and Molecular Life Sciences.2015; 72(4): 773. CrossRef

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