The role of protein disulphide-isomerase A3 as autoantigen in the pathogenesis of autoimmune thyroiditis and related brain damage in adult mice

Yang, Wenqing; Xiang, Yang; Zhang, Hongmei; Shan, Zhongyan; Li, Jing; Wang, Teng

doi:10.1016/j.clim.2020.108350

Cited by 9 publications

(6 citation statements)

References 51 publications

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“…Finally, autoantibodies or T cells against virtually all DAMPs involved in the sensing of RCD as immunogenic, including calreticulin (CALR) 243 , PDIA3 (refs. [244][245][246][247] ), ANXA1 (refs. 248,249 ) and HMGB1 (refs.…”

Section: Box 1 | Potential Implication Of Icd In Non-infectious Non-m...mentioning

confidence: 99%

Immunogenic cell stress and death

et al. 2022

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Section: Box 1 | Potential Implication Of Icd In Non-infectious Non-m...mentioning

confidence: 99%

Immunogenic cell stress and death

et al. 2022

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“…It seems more likely that a cross-reactive autoantigen present in brain and thyroid could be involved, and protein disulphide-isomerase A3 has been investigated as one such candidate. Mice immunised with protein disulphide-isomerase A3 develop an elevated TSH and impaired learning and memory, as well as antibody-mediated complement fixation in both thyroid and brain tissue [52].…”

Section: Associations With Htmentioning

confidence: 99%

An update on the pathogenesis of Hashimoto’s thyroiditis

Weetman

2020

J Endocrinol Invest

119

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It is 70 years since Noel Rose embarked on his pioneering studies that lead to the discovery of autoimmune thyroiditis and the elucidation of Hashimoto’s thyroiditis. This short review to honour his passing focuses on the developments in our understanding of the causes and pathogenesis of HT over the last five years. Recent genetic studies have reported heritability estimates for HT and associated diseases for the first time, and emphasised the complexity of the genetic factors involved, including monogenic forms of HT. Environmental factors continue to be elucidated, especially as a side effect of drugs which modulate the immune system therapeutically. Regarding pathogenetic mechanisms, multiple cytokine networks have been identified which involve the thyroid cells in a circuit of escalating proinflammatory effects, such as the expression of inflammasome components, and an array of different defects in T regulatory cells may underlie the loss of self-tolerance to thyroid autoantigens. Finally, a number of studies have revealed fresh insights into disease associations with HT which may have both pathological and clinical significance, the most intriguing of which is a possible direct role of the autoimmune process itself in causing some of the persistent symptoms reported by a minority of patients with levothyroxine-treated HT.

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“…These results indicate that both ENO1-P6Ab and PDIA3Ab are independent risk factors for pregnancy loss among euthyroid TAI women. Our previous studies have suggested that they may be involved in the development of extrathyroidal damage (e.g., encephalopathy) through different mechanisms in TAI individuals ( 18 , 38 ), which needs to be further investigated for the occurrence of miscarriage.…”

Section: Resultsmentioning

confidence: 99%

“…However, this study has shown that they are both independent risk factors for the occurrence of TAI-related miscarriage with synergistic additive effects. Our previous studies have suggested that the target autoantigens and potential mechanisms are different for ENO1Abs and PDIA3Abs ( 14 , 38 ). Although this study did not directly determine some other NOSA, including ANA and aPLs, and those participants with a known personal history of other chronic or autoimmune inflammatory diseases, including ANA or aPLs positivity, had been excluded from this study, we would conduct a larger-scale prospective study to further observe the relationship between the expressions of all known NOSA, including ANA and multiple aPLs, and the occurrence of miscarriage in euthyroid TAI women in the future, so as to establish a biomarker panel for better predicting their pregnancy loss risk.…”

Section: Discussionmentioning

confidence: 99%

A Predictive Role of Autoantibodies Against the Epitope aa168–183 of ENO1 in the Occurrence of Miscarriage Related to Thyroid Autoimmunity

Liu

Wang

et al. 2022

Front. Immunol.

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ObjectiveThe aim of the research is to study the association between the serum levels of autoantibodies against one important epitope (168FMILPVGAANFREAMR183, designated as P6) of α-enolase (ENO1-P6Abs) and miscarriage among euthyroid females with thyroid autoimmunity (TAI).MethodsAnti-ENO1-P6 total IgG was investigated in 432 euthyroid women, and its four subclasses were analyzed in 184 euthyroid women. The serum FT4, TSH, TgAb, and TPOAb levels were determined using an electrochemiluminescence immunoassay. The serum ENO1-P6Ab and anti-protein disulfide isomerase A3 autoantibody (PDIA3Ab) levels were determined using an enzyme-linked immunosorbent assay.ResultsThe serum levels of anti-ENO1-P6 total IgG, IgG2, IgG3, and IgG4 were significantly higher in euthyroid TAI females than in non-TAI controls. Additionally, anti-ENO1-P6 total IgG and its 4 subtypes were all markedly higher in euthyroid TAI females with pregnancy loss than those without miscarriage. Moreover, logistic regression analysis showed that highly expressed anti-ENO1-P6 total IgG, IgG1, IgG2, and IgG3 subtypes in the serum were all independent risk factors for euthyroid TAI-related miscarriage, and its IgG1 was also for non-TAI-related abortion. According to the trend test, the prevalence of miscarriage was increased in a titer-dependent manner with the raised levels of serum anti-ENO1-P6 total IgG and IgG1, IgG2, and IgG3 subtypes among euthyroid TAI females. The receiver operating characteristic curve analysis of anti-ENO1-P6 total IgG and IgG1, IgG2, and IgG3 subclass expressions in the serum for miscarriage prediction in euthyroid TAI females exhibited that the total areas under the curves were 0.773 ± 0.041, 0.761 ± 0.053, 0.827 ± 0.043, and 0.760 ± 0.050, respectively (all P <0.0001). Their corresponding optimal cut-off OD450 values were 0.68 (total IgG), 0.26 (IgG1), 0.97 (IgG2), and 0.48 (IgG3), with sensitivities of 70.8, 87.5, 83.3, and 85.4%, and specificities of 70.8, 59.1, 77.3, and 56.8%, respectively. There was an additive interaction between serum anti-ENO1-P6 and anti-PDIA3 total IgGs on the development of miscarriage (RERI = 23.6, AP = 0.79, SI = 5.37).ConclusionThe highly expressed ENO1-P6Abs may be important risk factors for euthyroid TAI-related miscarriage. The serum levels of ENO1-P6Abs may become good predictive markers for pregnancy loss in euthyroid TAI females, especially its IgG2 subclass expression.

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The role of protein disulphide-isomerase A3 as autoantigen in the pathogenesis of autoimmune thyroiditis and related brain damage in adult mice

Cited by 9 publications

References 51 publications

Immunogenic cell stress and death

Immunogenic cell stress and death

An update on the pathogenesis of Hashimoto’s thyroiditis

A Predictive Role of Autoantibodies Against the Epitope aa168–183 of ENO1 in the Occurrence of Miscarriage Related to Thyroid Autoimmunity

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