ketendoКлиническая и экспериментальная тиреоидологияClinical and experimental thyroidology1995-54722310-3787Endocrinology Research Centre10.14341/ket20117219-27ketendo-4358Research ArticleСтатьиArticlesПопуляция антитиреоидных аутоантител как источник антител различных уровней специфичности и функциональности: клиническая значимость феномена комбинаторики при мониторинге пациентов с аутоиммунными заболеваниями щитовидной железыPopulation of antithyroid autoantibodies as a source of antibodies of various levels of specificity and functionality: the clinical importance of a phenomenon of combination theory at monitoring of patients with autoimmune diseases of a thyroid glandAndreevaA V

врач-эндокринолог, ассистент кафедры эндокринологии и диабетологии ГОУ ВПО МГМСУ Росздрава

_1410_@rambler.ruSuchkovaE N

канд. мед. наук, доцент кафедры терапии с курсом эндокринологии Астраханской медицинской академии им. А.В. Луначарского

-GadjievaS I

ординатор ГОУ ВПО Первого МГМУ им. И.М.Сеченова

-MkrtumyanA M

доктор мед. наук, профессор, заведующий кафедрой эндокринологии и диабетологии ГОУ ВПО МГМСУ Росздрава

-GrishinaT I

доктор мед. наук, профессор, заведующая кафедрой клинической иммунологии ГОУ ВПО МГМСУ Росздрава

-SuchkovS V

доктор мед. наук, профессор кафедры клинической иммунологии лечебного факультета ГОУ ВПО МГМСУ Росздрава, профессор кафедры общей патологии ГОУ ВПО Первого МГМУ им. И.М. Сеченова

-NotkinsA L

доктор наук, профессор, заведующий отделом экспериментальной медицины и иммунологии Национального института здоровья, Бетезда, Мэриленд, США

-20111506201172ТОМ 7, №2 (2011)1927Copyright © Andreeva A.V., Suchkova E.N., Gadjieva S.I., Mkrtumyan A.M., Grishina T.I., Suchkov S.V., Notkins A.L., 20112011Andreeva A.V., Suchkova E.N., Gadjieva S.I., Mkrtumyan A.M., Grishina T.I., Suchkov S.V., Notkins A.L.Andreeva A.V., Suchkova E.N., Gadjieva S.I., Mkrtumyan A.M., Grishina T.I., Suchkov S.V., Notkins A.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.cet-endojournals.ru/jour/article/view/4358

В обзоре литературы обсуждается роль и клинико-патологическая значимость антитиреоидных аутоантител (аутоАТ), различающихся по специфичности , а именно АТ к тиреоглобулину (АТ-ТГ) и АТ к тиреоидной пероксидазе (АТ-ТПО), анти-TGPO, и функциональности , а именно АТ-протеаз, в патогенезе аутоиммунных заболеваний щитовидной железы (ЩЖ) и возможности их использования в современной диагностике аутоиммунных заболеваний ЩЖ.

The review of literature is dedicated to comparative analysis of pathogenetic and clinicodiagnostic significance of antithyroid autoantibodies (autoAB) differing in their specificity (АB to thyroglobulin (anti-TG) and АB to thyroid peroxidase (anti-TPO), anti-TGPO), and functionality TG- and TPO-antibodies, namely antibodies-proteases in pathogenesis autoimmune diseases thyroid gland and possibility of their use in modern diagnostics of autoimmune thyroid diseases.

антитиреоидные аутоантитела (аутоАТ)антитела-протеазыфункциональность аутоАТАТ-ТГ аутоАТАТ-ТПО аутоАТанти-TGPOantithyroid auto-ABAB-proteasesAB-functionalityanti-TG auto-ABanti-TPO auto-ABanti-TGPO auto-ABReferencesВоробьев И.И., Пономаренко Н.А., Решетняк А.В. и др. Каталитические антитела в медицине: Специфическая деградация аутоантигенов и новые подходы к инактивации патогенов // Мол. мед. 2004. №3. С. 48–55.Воробьев И.И., Пономаренко Н.А., Решетняк А.В. и др. Каталитические антитела в медицине: Специфическая деградация аутоантигенов и новые подходы к инактивации патогенов // Мол. мед. 2004. №3. С. 48–55.Дедов И.И., Трошина Е.А, Антонова С.С. и др. Аутоиммунные заболевания щитовидной железы: состояние проблемы // Пробл. эндокринол. 2002. Т. 48. №2. С. 6–13.Дедов И.И., Трошина Е.А, Антонова С.С. и др. Аутоиммунные заболевания щитовидной железы: состояние проблемы // Пробл. эндокринол. 2002. Т. 48. №2. С. 6–13.Иванова Е.В., Богатырева З.И., Исаева М.А. и др. Антитиреоидные антитела различных уровней специфичности в патогенезе и диагностике аутоиммунных заболеваний щитовидной железы // Тер. арх. 2009. №10. С. 54–56.Иванова Е.В., Богатырева З.И., Исаева М.А. и др. Антитиреоидные антитела различных уровней специфичности в патогенезе и диагностике аутоиммунных заболеваний щитовидной железы // Тер. арх. 2009. №10. С. 54–56.Исаева М.А., Богатырева З.И., Андреева А.И. др. Антителапротеазы при аутоиммунных заболеваниях щитовидной железы: патогенетические и клинические аспекты // Врач. 2009. №7. С. 87–100.Исаева М.А., Богатырева З.И., Андреева А.И. др. Антителапротеазы при аутоиммунных заболеваниях щитовидной железы: патогенетические и клинические аспекты // Врач. 2009. №7. С. 87–100.Мисиков В.К., Кимова М.В., Дурова О.М. и др. Каталитические аутоантитела при рассеянном склерозе // Бюл. экспер. биол. 2005. №1. С. 98–101.Мисиков В.К., Кимова М.В., Дурова О.М. и др. Каталитические аутоантитела при рассеянном склерозе // Бюл. экспер. биол. 2005. №1. С. 98–101.Пономаренко Н.А., Дурова О.М., Воробьев И.И. и др. К вопросу о каталитической активности аутоантител при рассеянном склерозе // Докл. АН (биохимия, биофизика, молекулярная биология). 2004. Т. 395. №6. С. 839–842.Пономаренко Н.А., Дурова О.М., Воробьев И.И. и др. К вопросу о каталитической активности аутоантител при рассеянном склерозе // Докл. АН (биохимия, биофизика, молекулярная биология). 2004. Т. 395. №6. С. 839–842.Шилин Д.Е. Исследование антитиреоидных антител и тироглобулина в диагностике и контроле терапии заболеваний щитовидной железы // Лаборатория. 1998. №11. С. 3–6.Шилин Д.Е. Исследование антитиреоидных антител и тироглобулина в диагностике и контроле терапии заболеваний щитовидной железы // Лаборатория. 1998. №11. С. 3–6.Amino N., Kubota S., Morita S. et al. Quantitative Measurement of Anti-TSH Receptor Antibodies is Useful for the Evaluation of Treatment Effect // Thyroid. 2007. V. 17(1). P. 85–86.Amino N., Kubota S., Morita S. et al. Quantitative Measurement of Anti-TSH Receptor Antibodies is Useful for the Evaluation of Treatment Effect // Thyroid. 2007. V. 17(1). P. 85–86.Bogner U., Kotulla P., Peters H. et al. Thyroid peroxidase/microsomal antibodies are not identical with thyroid cytotoxic antibodies in autoimmune thyroiditis // Acta Endocr. 1990. V. 123(4). P. 431–437.Bogner U., Kotulla P., Peters H. et al. Thyroid peroxidase/microsomal antibodies are not identical with thyroid cytotoxic antibodies in autoimmune thyroiditis // Acta Endocr. 1990. V. 123(4). P. 431–437.Bulow Pedersen I., Laurberg P., Knudsen N. et al. A population study of the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure // Clin. Endocr. 2005. V. 62(6). P. 713–720.Bulow Pedersen I., Laurberg P., Knudsen N. et al. A population study of the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure // Clin. Endocr. 2005. V. 62(6). P. 713–720.Сhardes T., Chapal N., Bresson D. et al. The human anti-thyroid peroxidase autoantibody repertoire in Graves' and Hashimoto's autoimmune thyroid diseases // Immunogenetics. 2002. V. 54(3). P. 141–157.Сhardes T., Chapal N., Bresson D. et al. The human anti-thyroid peroxidase autoantibody repertoire in Graves' and Hashimoto's autoimmune thyroid diseases // Immunogenetics. 2002. V. 54(3). P. 141–157.Chiovato L., Latrofa F., Braverman L.E. et al. Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens // Ann. Intern. Med. 2003. V. 2. 139(5 Pt 1). P. 346–351.Chiovato L., Latrofa F., Braverman L.E. et al. Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens // Ann. Intern. Med. 2003. V. 2. 139(5 Pt 1). P. 346–351.Demers L.M., Spencer C.A. Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease // Clin. Endocr. 2003. V. 58(2). P. 138–140.Demers L.M., Spencer C.A. Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease // Clin. Endocr. 2003. V. 58(2). P. 138–140.Demirbilek H., Kandemir N., Gonc E.N. et al. Hashimoto's thyroiditis in children and adolescents: a retrospective study on clinical, epidemiological and laboratory properties of the disease // J. Pediatr. Endocr. Met. 2007. V. 20(11). P. 1199–205.Demirbilek H., Kandemir N., Gonc E.N. et al. Hashimoto's thyroiditis in children and adolescents: a retrospective study on clinical, epidemiological and laboratory properties of the disease // J. Pediatr. Endocr. Met. 2007. V. 20(11). P. 1199–205.Estienne V., Duthoit C., Costanzo V.D. et al. Multicenter study on TGPO autoantibody prevalence in various thyroid and non-thyroid diseases; relationships with thyroglobulin and thyroperoxidase autoantibody parameters // Eur. J. Endocrinol. 1999. V. 141(6). P. 563–569.Estienne V., Duthoit C., Costanzo V.D. et al. Multicenter study on TGPO autoantibody prevalence in various thyroid and non-thyroid diseases; relationships with thyroglobulin and thyroperoxidase autoantibody parameters // Eur. J. Endocrinol. 1999. V. 141(6). P. 563–569.Giovanella L., Ceriani L., Ghelfo A. et al. Second-generation thyrotropin receptor antibodies assay and quantitative thyroid scintigraphy in autoimmune hyperthyroidism // Horm. Met. Res. 2008. V. 40(7). P. 484–486.Giovanella L., Ceriani L., Ghelfo A. et al. Second-generation thyrotropin receptor antibodies assay and quantitative thyroid scintigraphy in autoimmune hyperthyroidism // Horm. Met. Res. 2008. V. 40(7). P. 484–486.Gleicher N., Barad D., Weghofer A. Functional autoantibodies, a new paradigm in autoimmunity? // Autoimmun. Rev. 2007. V. 7(1). P. 42–45.Gleicher N., Barad D., Weghofer A. Functional autoantibodies, a new paradigm in autoimmunity? // Autoimmun. Rev. 2007. V. 7(1). P. 42–45.Tada H., Mizuta I., Takano T. et al. Blocking-type anti-TSH receptor antibodies and relathion to responsiveness to antithyroid drug therapy and remission in Graves' disease // Clin. Endocr. 2003. V. 58(4). P. 403–408.Tada H., Mizuta I., Takano T. et al. Blocking-type anti-TSH receptor antibodies and relathion to responsiveness to antithyroid drug therapy and remission in Graves' disease // Clin. Endocr. 2003. V. 58(4). P. 403–408.Jasani B., Ternynck T., Lazarus J.H. et al. Natural antibody status in patients with Hashimoto's thyroiditis // J. Clin. Lab. Immunol. 1999. V. 51(1). P. 9–12.Jasani B., Ternynck T., Lazarus J.H. et al. Natural antibody status in patients with Hashimoto's thyroiditis // J. Clin. Lab. Immunol. 1999. V. 51(1). P. 9–12.Kotani T. Anti-TPO autoantibodies // Rinsho Byori. 1998. V. 46(4). P. 324–330.Kotani T. Anti-TPO autoantibodies // Rinsho Byori. 1998. V. 46(4). P. 324–330.Кratzch J., Fiedler G.M., Leichtle A. at al. New reference intervals for hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid // Clin. Chem. 2005. V. 51(8). P. 1480–1486.Кratzch J., Fiedler G.M., Leichtle A. at al. New reference intervals for hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid // Clin. Chem. 2005. V. 51(8). P. 1480–1486.Kuwabara A, Kobayashi I. Microsomal antibody // Nippon Rinsho. 1999. V. 57(8). P. 1815–1818.Kuwabara A, Kobayashi I. Microsomal antibody // Nippon Rinsho. 1999. V. 57(8). P. 1815–1818.Lacroix-Desmazes S., Wootla B., Delignat S. et al. Pathophysiology of catalytic antibodies // Immunol. Lett. 2006. V. 103(1). P. 3–7.Lacroix-Desmazes S., Wootla B., Delignat S. et al. Pathophysiology of catalytic antibodies // Immunol. Lett. 2006. V. 103(1). P. 3–7.Lui C., Hermsen D., Domberg J. et al. Comparison of M22-based ELISA and human-TSH-receptor based luminescence assay for the measurement of thyrotropin receptor antibodies in patients with thyroid diseases // Horm. Met. Res. 2008. P. 479–483.Lui C., Hermsen D., Domberg J. et al. Comparison of M22-based ELISA and human-TSH-receptor based luminescence assay for the measurement of thyrotropin receptor antibodies in patients with thyroid diseases // Horm. Met. Res. 2008. P. 479–483.Mancini G., Carbonara A.O., Heremans J.F. Immunochemical quantitation of antigens by single radial immunodiffusion // Immunochemistry. 1965. V. 2(3). P. 235–254.Mancini G., Carbonara A.O., Heremans J.F. Immunochemical quantitation of antigens by single radial immunodiffusion // Immunochemistry. 1965. V. 2(3). P. 235–254.Mann K., Janssen O.E. Subclinical hypothyroidism - what level of TSH is an indication for substitution? // MMW Fortschr. Med. 2006. V. 2. 148(9). P. 26–29.Mann K., Janssen O.E. Subclinical hypothyroidism - what level of TSH is an indication for substitution? // MMW Fortschr. Med. 2006. V. 2. 148(9). P. 26–29.Mariotti S., Barbesino G., Caturegli P. et al. Assay of thyroglobulin in serum with thyroglobulin autoantibodies: an unobtainable goal? // J. Clin. Endocr. Met. 1995. V. 80(2). P. 468–472.Mariotti S., Barbesino G., Caturegli P. et al. Assay of thyroglobulin in serum with thyroglobulin autoantibodies: an unobtainable goal? // J. Clin. Endocr. Met. 1995. V. 80(2). P. 468–472.McIntosh R.S., Tandon N., Metcalfe R.A. et al. Cloning and analysis of IgM anti-thyroglobulin autoantibodies from patients with Hashimoto's thyroiditis // Biochim. Biophys. Acta. 1994. V. 29. 1227(3). P. 171–176.McIntosh R.S., Tandon N., Metcalfe R.A. et al. Cloning and analysis of IgM anti-thyroglobulin autoantibodies from patients with Hashimoto's thyroiditis // Biochim. Biophys. Acta. 1994. V. 29. 1227(3). P. 171–176.Moore D.C. Natural course of 'subclinical' hypothyroidism in childhood and adolescence // Arch. Pediatr. Adolesc. Med. 1996. V. 150(3). P. 293–297.Moore D.C. Natural course of 'subclinical' hypothyroidism in childhood and adolescence // Arch. Pediatr. Adolesc. Med. 1996. V. 150(3). P. 293–297.Morita T., Tamai H., Oshima A. et al. The occurrence of thyrotropin binding-inhibiting immunoglobulins and thyroid-stimulating antibodies in patients with silent thyroiditis // J. Clin. Endocr. Met. 1990. V. 71(4). P. 1051–1055.Morita T., Tamai H., Oshima A. et al. The occurrence of thyrotropin binding-inhibiting immunoglobulins and thyroid-stimulating antibodies in patients with silent thyroiditis // J. Clin. Endocr. Met. 1990. V. 71(4). P. 1051–1055.Nagataki S. The concept of Hashimoto disease. In: Nagataki S., Mori T., Torizuka K., eds. 80 Years of Hashimoto disease. Amsterdam: Elsevier Science, 1993. P. 539–545.Nagataki S. The concept of Hashimoto disease. In: Nagataki S., Mori T., Torizuka K., eds. 80 Years of Hashimoto disease. Amsterdam: Elsevier Science, 1993. P. 539–545.Nevinsky G.A., Buneva V.N. Human catalytic RNA- and DNA-hydrolyzing antibodies // J. Immunol. Methods. 2002. V. 263. P. 235–249.Nevinsky G.A., Buneva V.N. Human catalytic RNA- and DNA-hydrolyzing antibodies // J. Immunol. Methods. 2002. V. 263. P. 235–249.Ng H.P., Banga J.P., Kung A.W. Development of a murine model of autoimmune thyroiditis induced with homologous mouse thyroid peroxidase // Endocrinol. 2004. V. 145(2). P. 809–816.Ng H.P., Banga J.P., Kung A.W. Development of a murine model of autoimmune thyroiditis induced with homologous mouse thyroid peroxidase // Endocrinol. 2004. V. 145(2). P. 809–816.O'Leary P.C., Fedolema P.H., Michelangeli V.P. at al. Investigations of thyroid hormones antibodies based on a community health survey: the Busselton thyroid study // Clin. Endocr. 2006. V. 64(1). P. 97–104.O'Leary P.C., Fedolema P.H., Michelangeli V.P. at al. Investigations of thyroid hormones antibodies based on a community health survey: the Busselton thyroid study // Clin. Endocr. 2006. V. 64(1). P. 97–104.Ota H., Amino N., Morita S. at al. Quantitative measurement of thyroid blood flow for differentiation of painless thyroiditis from Graves' disease // Clin. Endocr. 2007. V. 67(1). P. 41–45.Ota H., Amino N., Morita S. at al. Quantitative measurement of thyroid blood flow for differentiation of painless thyroiditis from Graves' disease // Clin. Endocr. 2007. V. 67(1). P. 41–45.Outschoorn I.M., Hoffman W.H., Rose N.R. et al. Heritability of levels of autoantibodies to thyroid antigens using the method of plotting regression of offspring on midparent (ROMP) // Autoimmunity. 2007. V. 40(5). P. 366–371.Outschoorn I.M., Hoffman W.H., Rose N.R. et al. Heritability of levels of autoantibodies to thyroid antigens using the method of plotting regression of offspring on midparent (ROMP) // Autoimmunity. 2007. V. 40(5). P. 366–371.Paul S., Nishiyama Y., Planque S., Taguchi H. Theory of proteolytic antibody occurrence // Immunol. Lett. 2006. 103(1). Р. 8–16.Paul S., Nishiyama Y., Planque S., Taguchi H. Theory of proteolytic antibody occurrence // Immunol. Lett. 2006. 103(1). Р. 8–16.Rebuffat S.A., Nguyen B., Robert B. et al. Antithyroperoxidase antibody-dependent cytotoxicity in autoimmune thyroid disease // J. Clin. Endocr. Met. 2008. V. 93(3). P. 929–934.Rebuffat S.A., Nguyen B., Robert B. et al. Antithyroperoxidase antibody-dependent cytotoxicity in autoimmune thyroid disease // J. Clin. Endocr. Met. 2008. V. 93(3). P. 929–934.Rodien P., Madec A.M., Ruf J. et al. Antibody-dependent cell-mediated cytotoxicity in autoimmune thyroid disease: relationship to antithyroperoxidase antibodies// J. Clin. Endocr. Met. 1996. V. 81(7). P. 2595–2600.Rodien P., Madec A.M., Ruf J. et al. Antibody-dependent cell-mediated cytotoxicity in autoimmune thyroid disease: relationship to antithyroperoxidase antibodies// J. Clin. Endocr. Met. 1996. V. 81(7). P. 2595–2600.Rose N.R., Burek C.L. Autoantibodies to thyroglobulin in health and disease // Appl. Biochem. Biotechnol. 2000. V. 83 (Suppl. 1–3). P. 245–251.Rose N.R., Burek C.L. Autoantibodies to thyroglobulin in health and disease // Appl. Biochem. Biotechnol. 2000. V. 83 (Suppl. 1–3). P. 245–251.Santoh T., Watanabe M., Kuroda S. et al. Ratio of serum IgG3 to total IgG concentration and goiter size are independent factors in intractability of Graves' disease // Endocr. J. 2007. V. 54(6). P. 887–894.Santoh T., Watanabe M., Kuroda S. et al. Ratio of serum IgG3 to total IgG concentration and goiter size are independent factors in intractability of Graves' disease // Endocr. J. 2007. V. 54(6). P. 887–894.Takami H.E., Miyabe R., Kameyama K. Hashimoto's Thyroiditis // Wld J. Surg. 2008. V. 32(5). P. 688–692.Takami H.E., Miyabe R., Kameyama K. Hashimoto's Thyroiditis // Wld J. Surg. 2008. V. 32(5). P. 688–692.Trbojevic B., Djurica S. Diagnosis of autoimmune thyroid disease // Srp. Arh. Celok. Lek. 2005. V. 133 (Suppl. 1). P. 25–33.Trbojevic B., Djurica S. Diagnosis of autoimmune thyroid disease // Srp. Arh. Celok. Lek. 2005. V. 133 (Suppl. 1). P. 25–33.Ugurlu S., Caglar E., Yesim T. et al. Anti-Scl-70 antibodies in autoimmune hypothyroidism // J. Int. Med. Res. 2008. V. 36(1). P. 152–156.Ugurlu S., Caglar E., Yesim T. et al. Anti-Scl-70 antibodies in autoimmune hypothyroidism // J. Int. Med. Res. 2008. V. 36(1). P. 152–156.Watanabe M., Yamamoto N., Maruoka H. et al. Independent involvement of CD8+ CD25+ cells and thyroid autoantibodies in disease severity of Hashimoto's disease // Thyroid. 2002. V. 12(9). P. 801–808.Watanabe M., Yamamoto N., Maruoka H. et al. Independent involvement of CD8+ CD25+ cells and thyroid autoantibodies in disease severity of Hashimoto's disease // Thyroid. 2002. V. 12(9). P. 801–808.Wen W., Liu F. Autoantibodies Highly Increased in Patients with Thyroid Dysfunction // Cell. Molec. Immunol. 2007. V. 4 (3). P. 233–236.Wen W., Liu F. Autoantibodies Highly Increased in Patients with Thyroid Dysfunction // Cell. Molec. Immunol. 2007. V. 4 (3). P. 233–236.

The authors declare that there are no conflicts of interest present.