Preview

Clinical and experimental thyroidology

Advanced search

Evaluation of epitopes specificity of antibodies to thyroid peroxidase in autoimmune thyroid disorders

https://doi.org/10.14341/ket20117243-48

Abstract

The problem of the human antithyroid peroxidase autoantibodies epitopes heterogeneity diagnosed in case of Graves' disease and Hashimoto's thyroiditis has been researched using monoclonal antibodies to thyroid peroxidase. It was shown, that in the competition for the binding sites of thyroid peroxidase and autoantibodies taken from patients with Graves' disease and Hashimoto's thyroiditis sera participate 8 mAb to epitopes 1, 70, 82, 88, 2, 3, 77 and 79. The maxima of the binding inhibition has been marked for the conformation epitope mAb 3: in case of Graves' disease it amounts to 60.3 ± 12.7%, in case of Hashimoto's thyroiditis – 61.8 ± 32.2%. Moreover the level of the binding inhibition did not depend on the concentration of Ab to thyroid peroxidase in the sera of patient with Graves' as opposed to the serum of patients with Hashimoto's thyroiditis. Autoantibodies in the serum of the patientswith Hashimoto's thyroiditis inhibited the binding of mAb to epitope 77 much more effectively, than in the serum of the patients with: 36.3 ± 17.2 and 54.3 ± 9.6% (p ≤ 0.05).The obtained results represented the specific reaction of the autoantibodies to the certain thyroid peroxidase molecular patterns which corresponds to the literature data. It is possible to assume that the further research of the competitive interactions with other autoantibodies to monoclonal antibodies, not included in this trial, and widening of the different thyroid diseased patients' serum palette can expose new immunodominant thyroid peroxidase molecular patterns, forming antibodies for different diseases, and enable the development of diagnostics and control of the thyroid functions and applied therapy.

About the Authors

A Subkov

kand. med. nauk, starshiy nauchnyy sotrudnik laboratorii immunologicheskoy diagnostiki en- dokrinnykh zabolevaniy


V Sviridov

kand. med. nauk, zaveduyushchiy laboratoriey kletochnykh gibridov


G Kirillova

nauchnyy sotrudnik laboratorii immunologicheskoy diagnostiki endokrinnykh zabolevaniy


N Gavrilova

kand. biol. nauk, starshiy nauchnyy sotrudnik laboratorii kletochnykh gibridov


G Kusnezova

nauchnyy sotrudnik laboratorii immunologicheskoy diagnostiki endokrinnykh zabolevaniy


E Jakovleva

kand. biol. nauk, vedushchiy nauchnyy sotrudnie laboratorii kletochnykh gibridov


E Shamkina

laborant-issledovatel' laboratorii immunologicheskoy diagnostiki endokrinnykh zabolevaniy


N Kuzmina



References

1. Мельниченко Г.А. Аутоиммунный тиреоидит: клинические рекомендации российской ассоциации эндокринологов / Мат. 2-го Рос. тиреоидол. конгр. “Актуальные проблемы заболеваний щитовидной железы”, 20–21 ноября М., 2002. С. 5–18.

2. Мельниченко Г.А. Проблемы классификации и клинической диагностики узлового зоба / Мат. 2-го Рос. тиреоидол. конгр. “Актуальные проблемы заболеваний щитовидной железы”, 20–21 ноября 2002 г. М., C. 43–49.

3. Шилин Д.Е. Актуальные вопросы лабораторной диагностики заболеваний щитовидной железы (современные рекомендации международных организаций) // Лаборатория. 2002. №3. С. 22–25.

4. Трошина Е.А. К вопросу о недостатке и избытке йода в организме человека // Клин. экпер. тиреидол. 2010. Т. 6. №4. С. 9–16.

5. Weetman A.P. The potential immunological role of the thyroid cell in autoimmune thyroid disease // Thyroid. 1994. V. 4(4). P. 493–499.

6. Weetman A.P., Black C.M., Cohen S.B. et al. Affinity purification of IgG subclasses and the distribution of thyroid autoantibody reactivity in Hashimoto's thyroiditis // Scand. J. Immunol. 1989. V. 30. P. 73–82.

7. Weetman A.P. The role of T lymphocytes in thyroid-associated ophthalmopathy // Autoimmun. 1992. V. 13(1). P. 69–73.

8. Weetman A.P., Fung H.Y.M., Richards C.J., McGregor A.M. IgG subclass distribution and relative functional affinity of thyroid microsomal antibodies in postpartum thyroiditis // Eur. J. Clin. Invest. 1990. V. 20. P. 133–136.

9. Tandon N., Freeman M., Weetman A.P. T cell responses to synthetic thyroid peroxidase peptides in autoimmune thyroid disease // Clin. Exp. Immunol. 1991. V. 86. P. 56–60.

10. Tandon N., Yan S.L., Morgan B.P., Weetman A.P. Expression and function of multiple regulators of complement activation in autoimmune thyroid disease // Immunol. 1994. V. 81. P. 643–647.

11. Nagayama Y., Seto P., Rapoport B. Characterization, by molecular cloning, of smaller forms of thyroid peroxidase messenger ribonucleic acid in human thyroid cells as alternatively spliced transcripts // J. Clin. Endocrinol. Metab. 1990. V. 71(2). P. 384–390.

12. Portolano S., McLachlan S.M., Rapoport B. High affinity, thyroidspecific human autoantibodies displayed on the surface of filamentous phage use V genes similar to other autoantibodies. // J. Immunol. 1993. V. 151(5). P. 2839–2851.

13. Portolano S., Chazenbalk G.D., Seto P. et al. Recognition by recombinant autoimmune thyroid disease-derived Fab fragments of a dominant conformational epitope on human thyroid peroxi- dase // J. Clin. Invest. 1992. V. 90(3). P. 720–726.

14. Volpe R. B-lymphocytes in autoimmune thyroid diseases (AITD) // Rev. Endocr. Metab. Disord. 2000. V. 1 (1–2). P. 79–86.

15. Ruf J., Carayon P. Structural and functional aspects of thyroid peroxidase // Arch. Biochem. Biophys. 2006. V. 445. P. 269–277.

16. Ludgate M., Costagliola S.,Vassart G. Animal models of Graves' disease. In Graves' disease: pathogenesis and treatment / Ed. B. Rapoport, S.M. McLachlan. Massachusetts: Kluwer Acad. Publish. Norwell, 2000. P. 127–138.

17. Jeong H.J., Lee M.K., Choi I.J., Lee Y.B. Disribution of lymphocytic subpopulations infiltrated in thyroid glands of Graves disease // Yonsei Med. J. 1989. V. 30(2). P.118–124.

18. Paschke R., Vogg M., Swillens S., Usadel K.H. Correlation of microsomal antibodies with the intensity of the intrathyroidal autoimmune process in Graves' disease // J. Clin. Endocr. Metab. 1993. V. 77 (4). P. 939–943.

19. Кандрор В.И., Крюкова И.О., Крайнова С.И. Антитиреоидные антитела и аутоимунные заболевания // Пробл. эндокринол. 1997. Т. 43. №3. С. 28–30.

20. Bermann M., Magee M., Koenig R.G. et al. Differential autoantibody responses to thyroid peroxidase in patients with Graves' disease and Hashimoto's thyroiditis // J. Clin. Endocrinol. Metab. 1993. V. 77 (4). P. 1098–1101.

21. Ruf J., Toubert M.E., Czarnocka B. et al. Relationship between immunomogical structure and biochemical properties of human thyroid peroxidase // Endocr. 1989. V. 125. P. 1211–1218.

22. Bossowski A., Stasiak Barmuta A., Czarnocka B. et al. Applikation of mouse monoclonal antibodies for identifications of antigen regions of human thyroid peroxidase in adolescents with Graves disease and non-toxic multinodular goiter by flow cytometry // Autoimmun. 2005. V 38 (8). P. 605–611.

23. Ruf J., Czarnocka B., De Micco C., Duttoit C., Ferrand M., Carayon P. Thyroid peroxidase is the organ-specific “microsomal” autoantigen involved in thyroid autoimmunity. // Acta Endocr. Suppl. (Copenh).1987. V 281. P. 49–56.

24. Banga J.P., Mirakian R., Hammond L. et al. Characterization of monoclonal antibodies directed towards the microsomal/microvillar thyroid autoantigen recognized by Hashimoto autoatibodies // Clin. Exp. Immunol. 1986. V. 64 (30). P. 544–554.

25. Кузьмина Н.С., Яковлева И.В., Свиридов В.В. и др. Моноклональные антитела к человеческой пероксидазе щитовидной железы // Биотехнология. 2005. №1. С. 51–57.

26. Зубков А.В., Яковлева И.В., Свиридов В.В. и др. Моноклональные антитела в исследовании структуры тиреопероксидазы – ведущего аутоантигена щитовидной железы // Физиология и патология иммунной системы. 2005. Т 9. №8. С. 25–30.

27. Зубков А.В. Изучение эпитопной структуры пероксидазы щитовидной железы человека: Автореф. дис. … канд. мед. наук. М., 2006.

28. Кузьмина Н.С., Кузнецова Г.И., Яковлева И.В. и др. Разработка иммуноферментного количественного метода определения антител к пероксидазе щитовидной железы // Аллергия, астма и клиническая иммунология. 1999. №9. С. 145–147.


Review

For citations:


 ,  ,  ,  ,  ,  ,  ,   Evaluation of epitopes specificity of antibodies to thyroid peroxidase in autoimmune thyroid disorders. Clinical and experimental thyroidology. 2011;7(2):43-48. (In Russ.) https://doi.org/10.14341/ket20117243-48

Views: 449


ISSN 1995-5472 (Print)
ISSN 2310-3787 (Online)