Skip to main content

Advertisement

Log in

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

Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

This study surveyed the novel autoantigens expressed in the orbital fat tissue of patients with Graves’ orbitopathy (GO) and explored the possibility of the autoantibodies against novel autoantigens as biomarkers for GO.

Methods

We used immuno-proteomic methods to survey novel autoantigens expressed in the orbit fat tissue of GO patients and confirmed by enzyme-linked immunosorbent assay (ELISA).

Results

One protein spot (aldehyde dehydrogenase 2 (ALDH2)) revealed high reactivity with the GO serum than did the healthy control serum and was further verified by ELISA. We found that the plasma anti-ALDH2 antibody level was increased in GO patients compared to healthy control donors. In addition, anti-ALDH2 antibody level was correlated with GO activity classified by clinical activity score(r = 0.588, p < 0.001, using Pearson’s correlation).

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Perros P, Neoh C, Dickinson J (2009) Thyroid eye disease. BMJ 338:b560

    Article  PubMed  Google Scholar 

  2. Soeters MR, van Zeijl CJ, Boelen A, Kloos R, Saeed P, Vriesendorp TM, Mourits MP (2011) Optimal management of graves orbitopathy: a multidisciplinary approach. Neth J Med 69:302–308

    PubMed  CAS  Google Scholar 

  3. Bahn RS (2003) Clinical review 157: Pathophysiology of Graves’ ophthalmopathy: the cycle of disease. J Clin Endocrinol Metab 88:1939–1946. https://doi.org/10.1210/jc.2002-030010

    Article  PubMed  CAS  Google Scholar 

  4. Garrity JA, Bahn RS (2006) Pathogenesis of graves ophthalmopathy: implications for prediction, prevention, and treatment. Am J Ophthalmol 142:147–153. https://doi.org/10.1016/j.ajo.2006.02.047

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Gianoukakis AG, Khadavi N, Smith TJ (2008) Cytokines, Graves’ disease, and thyroid-associated ophthalmopathy. Thyroid 18:953–958. https://doi.org/10.1089/thy.2007.0405

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Gerding MN, van der Meer JW, Broenink M, Bakker O, Wiersinga WM, Prummel MF (2000) Association of thyrotrophin receptor antibodies with the clinical features of Graves’ ophthalmopathy. Clin Endocrinol 52:267–271

    Article  CAS  Google Scholar 

  7. Wall JR, Lahooti H (2010) Pathogenesis of thyroid eye disease--does autoimmunity against the TSH receptor explain all cases? Endokrynol Pol 61:222–227

    PubMed  CAS  Google Scholar 

  8. Kubota S, Gunji K, Ackrell BA, Cochran B, Stolarski C, Wengrowicz S, Kennerdell JS, Hiromatsu Y, Wall J (1998) The 64-kilodalton eye muscle protein is the flavoprotein subunit of mitochondrial succinate dehydrogenase: the corresponding serum antibodies are good markers of an immune-mediated damage to the eye muscle in patients with Graves’ hyperthyroidism. J Clin Endocrinol Metab 83:443–447. https://doi.org/10.1210/jcem.83.2.4553

    Article  PubMed  CAS  Google Scholar 

  9. Kahaly GJ, Bang H, Berg W, Dittmar M (2005) Alpha-fodrin as a putative autoantigen in Graves’ ophthalmopathy. Clin Exp Immunol 140:166–172. https://doi.org/10.1111/j.1365-2249.2004.02750.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Hrda P, Sterzl I, Vana S, Novak Z, Matucha P, Kromminga A (2007) Endocrine orbitopathy and significance of autoantibodies against 1D protein. Cas Lek Cesk 146:273–277

    PubMed  CAS  Google Scholar 

  11. Tsui S, Naik V, Hoa N, Hwang CJ, Afifiyan NF, Sinha Hikim A, Gianoukakis AG, Douglas RS, Smith TJ (2008) Evidence for an association between thyroid-stimulating hormone and insulin-like growth factor 1 receptors: a tale of two antigens implicated in Graves’ disease. J Immunol 181:4397–4405

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Lahooti H, Parmar KR, Wall JR (2010) Pathogenesis of thyroid-associated ophthalmopathy: does autoimmunity against calsequestrin and collagen XIII play a role? Clin Ophthalmol 4:417–425

    PubMed  PubMed Central  Google Scholar 

  13. Cheng KC, Huang HH, Hung CT, Chen CC, Wu WC, Suen JL, Chen KJ, Wu YJ, Chang CH (2013) Proteomic analysis of the differences in orbital protein expression in thyroid orbitopathy. Graefes Arch Clin Exp Ophthalmol 251:2777–2787. https://doi.org/10.1007/s00417-013-2446-9

    Article  PubMed  CAS  Google Scholar 

  14. Lu CM, Lin JJ, Huang HH, Ko YC, Hsu JL, Chen JC, Din ZH, Wu YJ (2014) A panel of tumor markers, calreticulin, annexin A2, and annexin A3 in upper tract urothelial carcinoma identified by proteomic and immunological analysis. BMC Cancer 14:363. https://doi.org/10.1186/1471-2407-14-363

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Mourits MP, Prummel MF, Wiersinga WM, Koornneef L (1997) Clinical activity score as a guide in the management of patients with Graves’ ophthalmopathy. Clin Endocrinol 47:9–14

    Article  CAS  Google Scholar 

  16. Barrio-Barrio J, Sabater AL, Bonet-Farriol E, Velazquez-Villoria A, Galofre JC (2015) Graves’ Ophthalmopathy: VISA versus EUGOGO classification, assessment, and management. J Ophthalmol 2015:249125. https://doi.org/10.1155/2015/249125

    Article  PubMed  PubMed Central  Google Scholar 

  17. Prabhakar BS, Bahn RS, Smith TJ (2003) Current perspective on the pathogenesis of Graves’ disease and ophthalmopathy. Endocr Rev 24:802–835. https://doi.org/10.1210/er.2002-0020

    Article  PubMed  CAS  Google Scholar 

  18. Douglas RS, Gupta S (2011) The pathophysiology of thyroid eye disease: implications for immunotherapy. Curr Opin Ophthalmol 22:385–390. https://doi.org/10.1097/ICU.0b013e3283499446

    Article  PubMed  PubMed Central  Google Scholar 

  19. Marchitti SA, Brocker C, Stagos D, Vasiliou V (2008) Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily. Expert Opin Drug Metab Toxicol 4:697–720. https://doi.org/10.1517/17425255.4.6.697

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Greenfield NJ, Pietruszko R (1977) Two aldehyde dehydrogenases from human liver. Isolation via affinity chromatography and characterization of the isozymes. Biochim Biophys Acta 483:35–45

    Article  PubMed  CAS  Google Scholar 

  21. Crabb DW, Matsumoto M, Chang D, You M (2004) Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology. Proc Nutr Soc 63:49–63

    Article  PubMed  CAS  Google Scholar 

  22. Jackson B, Brocker C, Thompson DC, Black W, Vasiliou K, Nebert DW, Vasiliou V (2011) Update on the aldehyde dehydrogenase gene (ALDH) superfamily. Hum Genomics 5:283–303

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Edassery SL, Shatavi SV, Kunkel JP, Hauer C, Brucker C, Penumatsa K, Yu Y, Dias JA, Luborsky JL (2010) Autoantigens in ovarian autoimmunity associated with unexplained infertility and premature ovarian failure. Fertil Steril 94:2636–2641. https://doi.org/10.1016/j.fertnstert.2010.04.012

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Kruit PJ, van der Gaag R, Broersma L, Kijlstra A (1986) Autoimmunity against corneal antigens. I. Isolation of a soluble 54 Kd corneal epithelium antigen. Curr Eye Res 5:313–320

    Article  PubMed  CAS  Google Scholar 

  25. Verhagen C, Mor F, Kipp JB, de Vos AF, van der Gaag R, Cohen IR (1999) Experimental autoimmune keratitis induced in rats by anti-cornea T-cell lines. Invest Ophthalmol Vis Sci 40:2191–2198

    PubMed  CAS  Google Scholar 

  26. Chen CH, Ferreira JC, Gross ER, Mochly-Rosen D (2014) Targeting aldehyde dehydrogenase 2: new therapeutic opportunities. Physiol Rev 94:1–34. https://doi.org/10.1152/physrev.00017.2013

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Matsuse H, Shimoda T, Fukushima C, Mitsuta K, Kawano T, Tomari S, Saeki S, Kondoh Y, Machida I, Obase Y, Asai S, Kohno S (2001) Screening for acetaldehyde dehydrogenase 2 genotype in alcohol-induced asthma by using the ethanol patch test. J Allergy Clin Immunol 108:715–719

    Article  PubMed  CAS  Google Scholar 

  28. Saravanan P, Dayan CM (2001) Thyroid autoantibodies. Endocrinol Metab Clin N Am 30:315–337 viii

    Article  CAS  Google Scholar 

  29. Swain M, Swain T, Mohanty BK (2005) Autoimmune thyroid disorders-an update. Indian J Clin Biochem 20:9–17. https://doi.org/10.1007/bf02893034

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Funding

This study was supported by Grant kmhk-98-024 from Kaohsiung Municipal Hsiao-Kang Hospital. The sponsor had no role in the design or conduct of this research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cheng-Hsien Chang.

Ethics declarations

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cheng, KC., Wu, YJ., Cheng, KH. et al. Autoantibody against aldehyde dehydrogenase 2 could be a biomarker to monitor progression of Graves’ orbitopathy. Graefes Arch Clin Exp Ophthalmol 256, 1195–1201 (2018). https://doi.org/10.1007/s00417-017-3894-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-017-3894-4

Keywords

Navigation