Prevalence of Thyroid Peroxidase and Thyroglobulin Autoantibodies in the Swedish Population

 

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Abstract

Autoimmune thyroid disease (AITD) may be detected prior to clinical symptoms through the presence of autoantibodies against thyroid peroxidase (TPOab), thyroglobulin (TGab), or both.

The present study aimed to develop a novel radiobinding assay (RBA) for TPOab and to determine the prevalence of TPOab and TGab in the Swedish population.

Patient samples from 27 newly diagnosed Graves’ disease patients in longitudinal follow-up and 124 AITD autoantibody-positive children in prospective follow-up for increased risk of type 1 diabetes were included to validate the novel RBA for TPO. The results of RBA were compared with those obtained by commercial radioimmunoassay (RIA) and electrochemiluminescence (ECL). Furthermore, 476 serum samples from adult blood donors and 297 from 13-year-old school children were analyzed for the presence of TPOab and TGab.

Receiver operating characteristics analysis for the novel TPOab resulted in an area under curve (AUC) value of 0.82 (p<0.0001), a sensitivity of 77.8%, and a specificity of 91.9% in adult blood donors, and an AUC value of 0.70 (p<0.0001), a sensitivity of 53.2% and a specificity of 95.3% in the 13-year-old school children, respectively. TPOab levels in RBA correlated with both ECL (r=0.8950, p<0.0001) and RIA (r=0.9295, p<0.0001). The prevalence of TPOab and TGab was 6.3% and 7.6% in adult blood donors and 2.9 and 3.7% in 13-year-old school children.

In conclusion, a novel RBA for the determination of TPOab was developed and validated with current methodologies. This study also reports an increasing prevalence of thyroid autoantibodies from adolescence to adulthood.

Publication History

Received: 04 December 2022
Received: 21 February 2023

Accepted: 27 March 2023

Article published online:
28 June 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

• References

• 1 Fröhlich E, Wahl R. Thyroid autoimmunity: Role of anti-thyroid antibodies in thyroid and extra-thyroidal diseases. Front Immunol 2017; 8 DOI: 10.3389/fimmu.2017.00521.
  CrossrefPubMedGoogle Scholar
• 2 Antonelli A, Ferrari SM, Corrado A. et al. Autoimmune thyroid disorders. Autoimmun Rev 2015; 14: 174-180 DOI: 10.1016/j.autrev.2014.10.016.
  CrossrefPubMedGoogle Scholar
• 3 Ghoraishian SM, Hekmati Moghaddam SH, Afkhami-Ardekani M. Relationship between anti-thyroid peroxidase antibody and thyroid function test. Iran J Immunol 2006; 3: 146-149
  PubMedGoogle Scholar
• 4 Hollowell JG, Staehling NW, Flanders WD. et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002; 87: 489-499 DOI: 10.1210/jcem.87.2.8182.
  CrossrefPubMedGoogle Scholar
• 5 Gora M, Gardas A, Wiktorowicz W. et al. Evaluation of conformational epitopes on thyroid peroxidase by antipeptide antibody binding and mutagenesis. Clin Exp Immunol 2004; 136: 137-144 DOI: 10.1111/j.1365-2249.2004.02422.x.
  CrossrefPubMedGoogle Scholar
• 6 Gardas A, Watson PF, Hobby P. et al. Human thyroid peroxidase: Mapping of autoantibodies, conformational epitopes to the enzyme surface. Redox Report 2000; 5: 237-241 DOI: 10.1179/135100000101535681.
  CrossrefPubMedGoogle Scholar
• 7 Arscott PL, Koenig RJ, Kaplan MM. et al. Unique autoantibody epitopes in an immunodominant region of thyroid peroxidase (*). J Biol Chem 1996; 271: 4966-4973 DOI: 10.1074/jbc.271.9.4966.
  CrossrefPubMedGoogle Scholar
• 8 McLachlan SM, Rapoport B. Thyroid autoantibodies display both “Original Antigenic Sin” and epitope spreading. Front Immunol 2017; 8: 1845-1845 DOI: 10.3389/fimmu.2017.01845.
  CrossrefPubMedGoogle Scholar
• 9 Bresson D, Cerutti M, Devauchelle G. et al. Localization of the discontinuous immunodominant region recognized by human anti-thyroperoxidase autoantibodies in autoimmune thyroid diseases. J Biol Chem 2003; 278: 9560-9569 DOI: 10.1074/jbc.M211930200.
  CrossrefPubMedGoogle Scholar
• 10 Liu E, Eisenbarth GS. Accepting clocks that tell time poorly: Fluid-phase versus standard ELISA autoantibody assays. Clin Immunol 2007; 125: 120-126 DOI: 10.1016/j.clim.2007.08.005.
  CrossrefPubMedGoogle Scholar
• 11 McLachlan SM, Rapoport B. Thyroid autoantibodies display both “Original Antigenic Sin” and epitope spreading. Front Immunol 2017; 8: 1845 DOI: 10.3389/fimmu.2017.01845.
  CrossrefPubMedGoogle Scholar
• 12 Pihoker C, Gilliam LK, Hampe CS. et al. Autoantibodies in diabetes. Diabetes 2005; 54: S52-S61 DOI: 10.2337/diabetes.54.suppl_2.s52.
  CrossrefPubMedGoogle Scholar
• 13 Falorni A, Ortqvist E, Persson B. et al. Radioimmunoassays for glutamic acid decarboxylase (GAD65) and GAD65 autoantibodies using 35S or 3H recombinant human ligands. J Immunol Methods 1995; 186: 89-99 DOI: 10.1016/0022-1759(95)00139-2.
  CrossrefPubMedGoogle Scholar
• 14 Kohno Y, Yamaguchi F, Saito K. et al. Anti-thyroid peroxidase antibodies in sera from healthy subjects and from patients with chronic thyroiditis: Differences in the ability to inhibit thyroid peroxidase activities. Clin Exp Immunol 1991; 85: 459-463 DOI: 10.1111/j.1365-2249.1991.tb05749.x.
  CrossrefPubMedGoogle Scholar
• 15 Kaczur V, Vereb G, Molnar I. et al. Effect of anti-thyroid peroxidase (TPO) antibodies on TPO activity measured by chemiluminescence assay. Clin Chem 1997; 43: 1392-1396
  CrossrefPubMedGoogle Scholar
• 16 Prentice LM, Phillips DIW, Sarsero D. et al. Geographical distribution of subclinical autoimmune thyroid disease in Britain: A study using highly sensitive direct assays for autoantibodies to thyroglobulin and thyroid peroxidase. Acta Endocrinol 1990; 123: 493-498 DOI: 10.1530/acta.0.1230493.
  CrossrefPubMedGoogle Scholar
• 17 McLeod DSA, Cooper DS. The incidence and prevalence of thyroid autoimmunity. Endocrine 2012; 42: 252-265 DOI: 10.1007/s12020-012-9703-2.
  CrossrefPubMedGoogle Scholar
• 18 O’Leary PC, Feddema PH, Michelangeli VP. et al. Investigations of thyroid hormones and antibodies based on a community health survey: The Busselton thyroid study. Clin Endocrinol (Oxf) 2006; 64: 97-104 DOI: 10.1111/j.1365-2265.2005.02424.x.
  CrossrefPubMedGoogle Scholar
• 19 Bjoro T, Holmen J, Krüger O. et al. Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trondelag (HUNT). Eur J Endocrinol 2000; 143: 639-647 DOI: 10.1530/eje.0.1430639.
  CrossrefPubMedGoogle Scholar
• 20 Li Y, Teng D, Shan Z. et al. Antithyroperoxidase and antithyroglobulin antibodies in a five-year follow-up survey of populations with different iodine intakes. J Clin Endocrinol Metab 2008; 93: 1751-1757 DOI: 10.1210/jc.2007-2368.
  CrossrefPubMedGoogle Scholar
• 21 Katsarou A, Gudbjörnsdottir S, Rawshani A. et al. Type 1 diabetes mellitus. Nat Rev Dis Primers 2017; 3: 17016 DOI: 10.1038/nrdp.2017.16.
  CrossrefPubMedGoogle Scholar
• 22 Caio G, Volta U, Sapone A. et al. Celiac disease: A comprehensive current review. BMC Medicine 2019; 17: 142 DOI: 10.1186/s12916-019-1380-z.
  CrossrefPubMedGoogle Scholar
• 23 Tozzoli R, Bizzaro N, Tonutti E. et al. Immunoassay of anti-thyroid autoantibodies: High analytical variability in second generation methods. 2002; 40: 568-573 DOI: 10.1515/CCLM.2002.098.
  CrossrefPubMedGoogle Scholar
• 24 Nilsson A-L, Vaziri-Sani F, Broberg P. et al. Serological evaluation of possible exposure to Ljungan virus and related parechovirus in autoimmune (type 1) diabetes in children. J Med Virol 2015; 87: 1130-1140 DOI: 10.1002/jmv.24127.
  CrossrefPubMedGoogle Scholar
• 25 Jonsdottir B, Larsson C, Lundgren M. et al. Childhood thyroid autoimmunity and relation to islet autoantibodies in children at risk for type 1 diabetes in the diabetes prediction in skåne (DiPiS) study. Autoimmunity 2018; 51: 228-237 DOI: 10.1080/08916934.2018.1519027.
  CrossrefPubMedGoogle Scholar
• 26 Grubin CE, Daniels T, Toivola B. et al. A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM. Diabetologia 1994; 37: 344-350 DOI: 10.1007/BF00408469.
  CrossrefPubMedGoogle Scholar
• 27 Kondrashova A, Viskari H, Haapala A-M. et al. Serological evidence of thyroid autoimmunity among schoolchildren in two different socioeconomic environments. J Clin Endocrinol Metab 2008; 93: 729-734 DOI: 10.1210/jc.2007-1644.
  CrossrefPubMedGoogle Scholar
• 28 van der Pals M, Ivarsson A, Norström F. et al. Prevalence of thyroid autoimmunity in children with celiac disease compared to healthy 12-year olds. Autoimmune Dis 2014; 2014: 417356 DOI: 10.1155/2014/417356.
  CrossrefPubMedGoogle Scholar
• 29 D’Aurizio F, Metus P, Ferrari A. et al. Definition of the upper reference limit for thyroglobulin antibodies according to the National Academy of Clinical Biochemistry guidelines: Comparison of eleven different automated methods. Auto Immun Highlights 2017; 8: 8 DOI: 10.1007/s13317-017-0096-3.
  CrossrefPubMedGoogle Scholar
• 30 Tozzoli R, D’Aurizio F, Ferrari A. et al. The upper reference limit for thyroid peroxidase autoantibodies is method-dependent: A collaborative study with biomedical industries. Clinica Chimica Acta 2016; 452: 61-65 DOI: 10.1016/j.cca.2015.10.025.
  CrossrefPubMedGoogle Scholar
• 31 Vanderpump MPJ, Tunbrldge WMG, French JM. et al. The incidence of thyroid disorders in the community: A twenty-year follow-up of the Whickham Survey. Clinical Endocrinology 1995; 43: 55-68 DOI: 10.1111/j.1365-2265.1995.tb01894.x.
  CrossrefPubMedGoogle Scholar
• 32 Yan YR, Gao XL, Zeng J. et al. The association between thyroid autoantibodies in serum and abnormal function and structure of the thyroid. J Int Med Res 2015; 43: 412-423 DOI: 10.1177/0300060514562487.
  CrossrefPubMedGoogle Scholar
• 33 Hansen PS, Brix TH, Iachine I. et al. The relative importance of genetic and environmental effects for the early stages of thyroid autoimmunity: A study of healthy Danish twins. Eur J Endocrinol 2006; 154: 29-38 DOI: 10.1530/eje.1.02060.
  CrossrefPubMedGoogle Scholar
• 34 Tozzoli R, D’Aurizio F, Ferrari A. et al. The upper reference limit for thyroid peroxidase autoantibodies is method-dependent: A collaborative study with biomedical industries. Clin Chim Acta 2016; 452: 61-65 DOI: 10.1016/j.cca.2015.10.025.
  CrossrefPubMedGoogle Scholar
• 35 Lampasona V, Pittman DL, Williams AJ. et al. Islet Autoantibody Standardization Program 2018 Workshop: Interlaboratory comparison of glutamic acid decarboxylase autoantibody assay performance. Clin Chem 2019; 65: 1141-1152 DOI: 10.1373/clinchem.2019.304196.
  CrossrefPubMedGoogle Scholar