Experimental evidence for alpha enolase as one potential autoantigen in the pathogenesis of both autoimmune thyroiditis and its related encephalopathy

Lu, Yihan; Qin, Juan; Xiang, Yang; Sun, Rongli; Feng, Yan; Zhang, Hongmei; Ding, Shuangning; Li, Jing; Shan, Zhongyan; Wang, Teng

doi:10.1016/j.intimp.2020.106563

Cited by 7 publications

(17 citation statements)

References 59 publications

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“…In the validation stage, we proved that α-enolase and VDAC1 autoantibodies were new representative targets for distinguishing patients with B-ALL from normal controls. To the best of our knowledge,this study was the rst report of the existence of autoantibodies against α-enolase and VDAC1 in serum from children with B-ALL by a proteomic approach,nevertheless, the α-enolase autoantibody was not all speci c to B-ALL serum and were found in the serum of patients with other tumors,as well as α-enolase antibodies were found in some autoimmune diseases [29][30][31] .The mechanism which α-enolase and VDAC1 induce immune response in B-ALL is unclear.…”

Section: Discussionmentioning

confidence: 77%

Identification and Validation of Serum Autoantibodies in Children with B-cell Acute Lymphoblastic Leukemia by Serological Proteome Analysis

Yang

Liu

et al. 2021

Preprint

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Purpose: Study was by intention to screen serum autoantibodies that may contribute to the early detection of B-cell acute lymphoblastic leukemia (B-ALL) in children.Patients and methods: The total protein from three pooled B-ALL cell lines(NALM-6, REH and BALL-1 cells) was separated using two-dimensional gel electrophoresis(2-DE), which was followed by Western blot by mixed serum from B-ALL patients (n=20) or healthy children(n=20). We obtained and analyzed the images of 2-D gel and Western blot by PDQuest software,and then identify the spots of immune responses in B-ALL samples compared with those in control samples.The proteins from spots were identified using mass spectrometry (MS). The autoantibodies against α-enolase and voltage-dependent anion-selective channel protein 1(VDAC1) were further validated on the use of enzyme-linked immunosorbent assay(ELISA). The protein expression levels of the candidate antigens α-enolase and VDAC1 in B-ALL were thoroughly studied by immunohistochemical analysis.Results: Six protein dots were identified with MS as Aconitase,apoptosis-inducing factor(AIF),dihydrolipoamide dehydrogenase(DLD), α-enolase,medium-chain acyl-CoA dehydrogenase(MCAD) and VDAC 1.The frequencies of autoantibodies against α-enolase and VDAC1 in children with B-ALL were 27% and 23%, respectively, which were significantly higher than those in normal controls(4% and 0). Immunohistochemical analysis showed the expression of α-enolase and VDAC1 was positive in 95% and 85% of B-ALL patients, respectively, but negative expression levels were showed in the control group. Conclusion: This study incidates that α-enolase and VDAC1 may be the antigen associated with B-ALL .α-enolase and VDAC1 autoantibodies may develop into potential serological markers of B-ALL in children.Other proteins also need to be confirmed in a large number of serum samples.

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Section: Discussionmentioning

confidence: 77%

Identification and Validation of Serum Autoantibodies in Children with B-cell Acute Lymphoblastic Leukemia by Serological Proteome Analysis

Yang

Liu

et al. 2021

Preprint

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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%

“…ENO1 has also been known as a SUPER protein and is expressed on the surface of early apoptotic cells, which can trigger an autoimmune response ( 15 , 16 , 57 ). ENO1Abs have been reported in various autoimmune diseases, such as Hashimoto’s encephalopathy (HE), Behcet’s disease, rheumatoid arthritis (RA), multiple sclerosis, cancer-associated retinopathy (CAR), and lupus nephritis, and its positivity prevalence in the serum is found to be about 6–83% ( 16 , 18 , 58 – 63 ). Our previous study found that ENO1 protein was expressed in thyroid tissue, and serum ENO1Ab levels were significantly increased in the mice with EAT established by only Tg immunization ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

“…The serum anti-ENO1-P6 total IgG and its 4 subclass levels were measured by ELISA as previously described with slight modification ( 18 ). The recombinant ENO1-P6 peptide (FMILPVGAANFREAMR) was synthesized by Sangon Biotech (Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

“…Their expression has also been found to be associated with unexplained recurrent miscarriage (uRM), endometriosis, premature ovarian failure, and tubal factor infertility ( 21 – 24 ). In our previous study, the increased serum levels of ENO1Abs were observed in mice with experimental autoimmune thyroiditis (EAT) induced only by Tg immunization ( 18 ). Those studies suggest that ENO1Abs may be involved in the development of TAI-related pregnancy loss.…”

Section: Introductionmentioning

confidence: 95%

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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 thyroid-stimulating hormone in regulating lipid metabolism: Implications for body–brain communication

Wang,

Wu,

Liu

et al. 2024

Neurobiology of Disease

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Experimental evidence for alpha enolase as one potential autoantigen in the pathogenesis of both autoimmune thyroiditis and its related encephalopathy

Cited by 7 publications

References 59 publications

Identification and Validation of Serum Autoantibodies in Children with B-cell Acute Lymphoblastic Leukemia by Serological Proteome Analysis

Identification and Validation of Serum Autoantibodies in Children with B-cell Acute Lymphoblastic Leukemia by Serological Proteome Analysis

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

The role of thyroid-stimulating hormone in regulating lipid metabolism: Implications for body–brain communication

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