Advertisement

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

  • Kai-Chun Cheng
  • Yu-Jen Wu
  • Kai-Hung Cheng
  • Kai-Yuan Cheng
  • Kuo-Jen Chen
  • Wen-Chuan Wu
  • Po-Yen Lee
  • Cheng-Hsien Chang
Oculoplastics and Orbit

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.

Keywords

Graves’ orbitopathy Autoantigen Proteomic analysis Aldehyde dehydrogenase 2 Orbital fat 

Notes

Funding/support

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.

Compliance with ethical standards

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.

References

  1. 1.
    Perros P, Neoh C, Dickinson J (2009) Thyroid eye disease. BMJ 338:b560CrossRefPubMedGoogle Scholar
  2. 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 69:302–308PubMedGoogle Scholar
  3. 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 CrossRefPubMedGoogle Scholar
  4. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 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 52:267–271CrossRefGoogle Scholar
  7. 7.
    Wall JR, Lahooti H (2010) Pathogenesis of thyroid eye disease--does autoimmunity against the TSH receptor explain all cases? Endokrynol Pol 61:222–227PubMedGoogle Scholar
  8. 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 PubMedCrossRefGoogle Scholar
  9. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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 146:273–277PubMedGoogle Scholar
  11. 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 181:4397–4405CrossRefPubMedPubMedCentralGoogle Scholar
  12. 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 4:417–425PubMedPubMedCentralGoogle Scholar
  13. 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 CrossRefPubMedGoogle Scholar
  14. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 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 47:9–14CrossRefGoogle Scholar
  16. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 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 CrossRefPubMedGoogle Scholar
  18. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Greenfield NJ, Pietruszko R (1977) Two aldehyde dehydrogenases from human liver. Isolation via affinity chromatography and characterization of the isozymes. Biochim Biophys Acta 483:35–45CrossRefPubMedGoogle Scholar
  21. 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 63:49–63CrossRefPubMedGoogle Scholar
  22. 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 5:283–303CrossRefPubMedPubMedCentralGoogle Scholar
  23. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 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 5:313–320CrossRefPubMedGoogle Scholar
  25. 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 40:2191–2198PubMedGoogle Scholar
  26. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 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 108:715–719CrossRefPubMedGoogle Scholar
  28. 28.
    Saravanan P, Dayan CM (2001) Thyroid autoantibodies. Endocrinol Metab Clin N Am 30:315–337 viiiCrossRefGoogle Scholar
  29. 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 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Kai-Chun Cheng
    • 1
    • 2
    • 3
  • Yu-Jen Wu
    • 4
  • Kai-Hung Cheng
    • 5
    • 6
  • Kai-Yuan Cheng
    • 7
  • Kuo-Jen Chen
    • 1
  • Wen-Chuan Wu
    • 2
    • 8
  • Po-Yen Lee
    • 2
  • Cheng-Hsien Chang
    • 2
    • 8
  1. 1.Department of OphthalmologyKaohsiung Municipal Hsiao-kang HospitalKaohsiungTaiwan
  2. 2.Department of OphthalmologyKaohsiung Medical University HospitalKaohsiungTaiwan
  3. 3.Department of OptometryShu-Zen junior College of Medicine and ManagementKaohsiungTaiwan
  4. 4.Department of Biological Science and TechnologyMeiho UniversityPingtungTaiwan
  5. 5.Division of Cardiology, Department of Internal MedicineKaohsiung Medical University HospitalKaohsiungTaiwan
  6. 6.Department of Internal Medicine, Faculty of Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  7. 7.Department of Otolaryngology, Head and Neck SurgeryMinistry of Health and Welfare Pingtung HospitalPingtungTaiwan
  8. 8.Department of Ophthalmology, Faculty of Medicine, College of MedicineKaohsiung Medical UniversityKaohsiungTaiwan

Personalised recommendations