Autoantibody against aldehyde dehydrogenase 2 could be a biomarker to monitor progression of Graves’ orbitopathy

Cheng, Kai‐Chun; Wu, Yu-Jen; Cheng, Kai-Hung; Cheng, Kai-Yuan; Chen, Kuo-Jen; Wu, Wen-Chuan; Lee, Po-Yen; Chang, Cheng-Hsien

doi:10.1007/s00417-017-3894-4

Cited by 10 publications

(6 citation statements)

References 25 publications

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“…These results may conflict with a retrospective study conducted in Korea and including 98 patients, in which the level of anti-TPO was slightly higher in the GO group than in the non-GO group [51]. Anti-aldehyde dehydrogenase 2 (ALDH2) antibody level is increased in GO compared with controls, and positively correlated with CAS (r = 0.588; p < 0.001) [67]. Anti-calsequestrin antibodies contain two isoforms: anti-calsequestrin antibodies 1 and 2.…”

Section: Antibodymentioning

confidence: 76%

The risk factors for Graves’ ophthalmopathy

Cao

Chen

et al. 2021

Graefes Arch Clin Exp Ophthalmol

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Purpose This review aimed to provide an overview of current research into the risk factors for Graves' ophthalmopathy (GO). Methods To find information about the risk factors for GO, the research database PubMed was searched and relevant articles were obtained to extract information about risk factors. Results Smoking has been widely accepted as an important risk factor and cigarette smoking cessation has been shown to improve the outcome and decrease the onset of GO. Radioactive iodine on the thyroid may induce hyperthyroidism and increase the occurrence of GO. Selenium deficiency is a risk factor for GO and the supplementation of selenium has been an adjuvant therapy. Decreasing stressful life events (SLE) may help improve GO. Imbalance in intestinal flora is essential to GO, with Yersinia enterocolitica and Escherichia coli both increased in the digestive tract of the individual with GO. In addition, controlling serum cholesterol may help improve GO since adipogenesis is an important pathological change in its pathogenesis. Considering the correlation between Graves' disease and GO, maintaining normal thyroid function hormone level is the first-line therapeutic strategy to prevent progression of GO. An increase in antibodies such as TSHR and IGF-1R is the main predictor of GO. Besides, gender and gene polymorphism are also risk factors towards GO. Conclusions Risk factors for GO arise from five sources: physical and chemical environment, social-psychological environment, biological environment, the human organism, and genetic codes. Risk factors within these categories may interact with each other and their mechanisms in promoting the development of GO are complex. Research into risk factors for GO may promote emerging fields related to GO such as control of autoantibodies and intestinal microbiota.

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Section: Antibodymentioning

confidence: 76%

The risk factors for Graves’ ophthalmopathy

Cao

Chen

et al. 2021

Graefes Arch Clin Exp Ophthalmol

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“…Aldehyde dehydrogenase 2 is a key enzyme in mitochondrial oxidation. Cheng and coworkers 34 reported higher serum levels of anti–aldehyde dehydrogenase 2 in TED patients compared with HC. The authors defined a cut-off value of aldehyde dehydrogenase 2 as mean concentration in the serum of HC plus 3 standard deviations.…”

Section: Resultsmentioning

confidence: 98%

Molecular Biomarkers in Thyroid Eye Disease: A Literature Review

Ueland,

Neset,

Methlie

et al. 2023

Ophthalmic Plastic &Amp; Reconstructive Surgery

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Purpose: Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves disease. Patients may be severely affected with eyelid retraction, exophthalmos, diplopia, pain, and threatened vision. Autoantibodies against thyroid-stimulating hormone receptor and insulin-like growth factor 1 receptor have shown associations with pathophysiological and clinical traits. Autoantibodies against thyroid-stimulating hormone receptor is in current clinical use as biomarker, but not with unambiguous diagnostic performance. A biomarker with high diagnostic accuracy and/or prognostic capability would be of immense value in diagnosing TED, especially in subclinical cases or when TED precedes the thyroid dysfunction. This article is a literature review on molecular biomarkers of TED. Methods: A literature search was performed using PubMed and Embase. Studies on molecular biomarkers in blood, tear fluid, and urine were included in the review. Results: Forty-six papers were included, of which 30, 14, and 2 studies on biomarkers in blood, tears, and urine, respectively. Fourteen of the papers evaluated the diagnostic performance of various biomarkers, 12 in blood and 2 in tears. Most studies evaluated single biomarkers, but 3 tested a panel of several markers. Except for autoantibodies against thyroid-stimulating hormone receptor, the reported diagnostic performances for the biomarkers were not confirmed in independent cohorts. In 32 studies, no or insufficient performance data were given, but the findings indicated involvement of various biologic mechanisms in TED including inflammation, oxidative stress, fibrosis, lipid metabolism, and ocular surface microflora. Conclusions: Currently, serum autoantibodies against thyroid-stimulating hormone receptor is the only molecular biomarker with clinical utility in patients with TED. Several potential biomarkers have been investigated, and particularly panels of multiple biomarkers in tears are promising. To improve patient care, biomarkers in TED should be studied further.

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“…In our previous study [12], we established an immune-proteomic model to discover the potential autoantigens in GO patients through enzyme-linked immunosorbent assay (ELISA). We determined that the increase in serum anti-ALDH 2 antibody suggested that ALDH 2 might serve as the target autoantigen as well in patients with GO.…”

Section: Discussionmentioning

confidence: 99%

“…Aside from TRAb, in our previous study, we have also identi ed a higher titer of an autoantibody against aldehyde dehydrogenase 2 (ALDH 2 ) in GO serum through experimental means [12]. According to the study, the another target autoantigen, probably in relation to ALDH 2 , made anti-ALDH 2 autoantibody a potential biomarker to predict the disease activity of GO.…”

Section: Introductionmentioning

confidence: 97%

Comparison of the correlation between serum autoantibodies against aldehyde dehydrogenase 2 and thyrotropin receptor in patients with Graves’ ophthalmopathy

Lin¹,

Chiu²,

Lee³

et al. 2023

Preprint

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Objectives: Graves’ ophthalmopathy (GO) is an autoimmune disorder characterized by orbital inflammation related to Graves’ disease. Identifying the titers of potential autoimmune target such as thyrotropin receptor autoantibody (TRAb) and anti-aldehyde dehydrogenase 2 (ALDH2) antibody could be valuable and convenient in evaluating clinical activity and severity of GO to provide necessary treatment. This study aims to investigate the correlations among serum titers of anti-ALDH2 antibody and TRAb, thyroid function and clinical activity of GO. Methods: We retrospectively reviewed the medical records of fifty GO patients to identify the correlation coefficients between anti-ALDH2 antibody and the Clinical Activity Score (CAS); anti-ALDH2 antibody and TRAb; and TRAb and thyroid-related biochemical parameters using Pearson’s correlation. Results: After the analysis, there was a positive significant association between anti-ALDH2 antibody and CAS (r=0.301, P=0.033); however, no relationship was found between anti-ALDH2 antibody and TRAb (r=0.109, P=0.452). Additionally, TRAb was correlated with T3 (r=0.333, P=0.018), free-T4 (r=0.336, P=0.017) and TSH (r=-0.315, P=0.026), yet not associated with CAS (r=-0.009, P=0.948) as well. Conclusions: Anti-ALDH2 antibody could be a suitable assessment tool to evaluate the clinical activity of GO for providing patients with necessary treatment. The significant correlation between anti-ALDH2 antibody and CAS indicated that it might be more specific to the orbital tissues in GO patients compared to TRAb, which is instead more specific to the thyroid function.

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Autoantibody against aldehyde dehydrogenase 2 could be a biomarker to monitor progression of Graves’ orbitopathy

Abstract: These increased levels of anti-ALDH2 antibody in GO serum suggested that ALDH2 could attribute target autoantigen in GO, and anti-ALDH2 autoantibody might serve as a biomarker for GO and help to predict disease activity.

Cited by 10 publications

References 25 publications

The risk factors for Graves’ ophthalmopathy

The risk factors for Graves’ ophthalmopathy

Molecular Biomarkers in Thyroid Eye Disease: A Literature Review

Comparison of the correlation between serum autoantibodies against aldehyde dehydrogenase 2 and thyrotropin receptor in patients with Graves’ ophthalmopathy

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