Skip to main content
Immunology logoLink to Immunology
. 1989 Jun;67(2):197–204.

Thyroid microsomal/thyroid peroxidase autoantibodies show discrete patterns of cross-reactivity to myeloperoxidase, lactoperoxidase and horseradish peroxidase.

J P Banga 1, R W Tomlinson 1, N Doble 1, E Odell 1, A M McGregor 1
PMCID: PMC1385257  PMID: 2546881

Abstract

The recent cloning of the thyroid peroxidase (TPO) has shown that it is identical to the thyroid microsomal antigen (TMA), a potent antigen involved in autoimmune thyroid disease (ATD), which shares significant sequence homology with myeloperoxidase. The present study shows that autoantibodies (aAb) to the TMA/TPO antigen cross-react with human leucocyte myeloperoxidase, bovine lactoperoxidase and horseradish peroxidase. Cross-reactivity to myeloperoxidase was only apparent by ELISA using reduced and alkylated antigen preparations or by immunoblotting following denaturation with SDS. Sequential absorption of sera on SDS-denatured thyroid microsomes immobilized on Sepharose-4B followed by absorption on native microsomes removed all aAb specificities to TMA/TPO and the three peroxidase preparations, giving compelling evidence on the genuine cross-reactive nature of these aAbs. Sera from different patients contain different qualitative and quantitative specificities of aAb to the TMA/TPO antigen, confirming the polyclonal nature of this autoimmune response.

Full text

PDF
200

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banga J. P., Mirakian R., Hammond L., Pryce G., Bidey S., Bottazzo F., Weetman A. P., McGregor A. M., Roitt I. M. Characterization of monoclonal antibodies directed towards the microsomal/microvillar thyroid autoantigen recognized by Hashimoto autoantibodies. Clin Exp Immunol. 1986 Jun;64(3):544–554. [PMC free article] [PubMed] [Google Scholar]
  2. Banga J. P., Pryce G., Hammond L., Roitt I. M. Structural features of the autoantigens involved in thyroid autoimmune disease: the thyroid microsomal/microvillar antigen. Mol Immunol. 1985 Jun;22(6):629–642. doi: 10.1016/0161-5890(85)90092-6. [DOI] [PubMed] [Google Scholar]
  3. Czarnocka B., Ruf J., Ferrand M., Carayon P., Lissitzky S. Purification of the human thyroid peroxidase and its identification as the microsomal antigen involved in autoimmune thyroid diseases. FEBS Lett. 1985 Oct 7;190(1):147–152. doi: 10.1016/0014-5793(85)80446-4. [DOI] [PubMed] [Google Scholar]
  4. Fujiyama K., Takemura H., Shibayama S., Kobayashi K., Choi J. K., Shinmyo A., Takano M., Yamada Y., Okada H. Structure of the horseradish peroxidase isozyme C genes. Eur J Biochem. 1988 May 2;173(3):681–687. doi: 10.1111/j.1432-1033.1988.tb14052.x. [DOI] [PubMed] [Google Scholar]
  5. Hamada N., Grimm C., Mori H., DeGroot L. J. Identification of a thyroid microsomal antigen by Western blot and immunoprecipitation. J Clin Endocrinol Metab. 1985 Jul;61(1):120–128. doi: 10.1210/jcem-61-1-120. [DOI] [PubMed] [Google Scholar]
  6. Hamada N., Jaeduck N., Portmann L., Ito K., DeGroot L. J. Antibodies against denatured and reduced thyroid microsomal antigen in autoimmune thyroid disease. J Clin Endocrinol Metab. 1987 Feb;64(2):230–238. doi: 10.1210/jcem-64-2-230. [DOI] [PubMed] [Google Scholar]
  7. Kajita Y., Morgan D., Parkes A. B., Rees Smith B. Labelling and immunoprecipitation of thyroid microsomal antigen. FEBS Lett. 1985 Aug 5;187(2):334–338. doi: 10.1016/0014-5793(85)81271-0. [DOI] [PubMed] [Google Scholar]
  8. Khoury E. L., Hammond L., Bottazzo G. F., Doniach D. Presence of the organ-specific 'microsomal' autoantigen on the surface of human thyroid cells in culture: its involvement in complement-mediated cytotoxicity. Clin Exp Immunol. 1981 Aug;45(2):316–328. [PMC free article] [PubMed] [Google Scholar]
  9. Kimura S., Ikeda-Saito M. Human myeloperoxidase and thyroid peroxidase, two enzymes with separate and distinct physiological functions, are evolutionarily related members of the same gene family. Proteins. 1988;3(2):113–120. doi: 10.1002/prot.340030206. [DOI] [PubMed] [Google Scholar]
  10. Kimura S., Kotani T., McBride O. W., Umeki K., Hirai K., Nakayama T., Ohtaki S. Human thyroid peroxidase: complete cDNA and protein sequence, chromosome mapping, and identification of two alternately spliced mRNAs. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5555–5559. doi: 10.1073/pnas.84.16.5555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Klebanoff S. J., Hamon C. B. Role of myeloperoxidase-mediated antimicrobial systems in intact leukocytes. J Reticuloendothel Soc. 1972 Aug;12(2):170–196. [PubMed] [Google Scholar]
  12. Kohno Y., Hiyama Y., Shimojo N., Niimi H., Nakajima H., Hosoya T. Autoantibodies to thyroid peroxidase in patients with chronic thyroiditis: effect of antibody binding on enzyme activities. Clin Exp Immunol. 1986 Sep;65(3):534–541. [PMC free article] [PubMed] [Google Scholar]
  13. Libert F., Ruel J., Ludgate M., Swillens S., Alexander N., Vassart G., Dinsart C. Thyroperoxidase, an auto-antigen with a mosaic structure made of nuclear and mitochondrial gene modules. EMBO J. 1987 Dec 20;6(13):4193–4196. doi: 10.1002/j.1460-2075.1987.tb02766.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Matheson N. R., Wong P. S., Travis J. Isolation and properties of human neutrophil myeloperoxidase. Biochemistry. 1981 Jan 20;20(2):325–330. doi: 10.1021/bi00505a015. [DOI] [PubMed] [Google Scholar]
  15. Miyasaki K. T., Wilson M. E., Cohen E., Jones P. C., Genco R. J. Evidence for and partial characterization of three major and three minor chromatographic forms of human neutrophil myeloperoxidase. Arch Biochem Biophys. 1986 May 1;246(2):751–764. doi: 10.1016/0003-9861(86)90332-2. [DOI] [PubMed] [Google Scholar]
  16. Portmann L., Hamada N., Heinrich G., DeGroot L. J. Anti-thyroid peroxidase antibody in patients with autoimmune thyroid disease: possible identity with anti-microsomal antibody. J Clin Endocrinol Metab. 1985 Nov;61(5):1001–1003. doi: 10.1210/jcem-61-5-1001. [DOI] [PubMed] [Google Scholar]
  17. ROITT I. M., LING N. R., DONIACH D., COUCHMAN K. G. THE CYTOPLASMIC AUTO-ANTIGEN OF THE HUMAN THYROID. I. IMMUNOLOGICAL AND BIOCHEMICAL CHARACTERISTICS. Immunology. 1964 Jul;7:375–393. [PMC free article] [PubMed] [Google Scholar]
  18. Seto P., Hirayu H., Magnusson R. P., Gestautas J., Portmann L., DeGroot L. J., Rapoport B. Isolation of a complementary DNA clone for thyroid microsomal antigen. Homology with the gene for thyroid peroxidase. J Clin Invest. 1987 Oct;80(4):1205–1208. doi: 10.1172/JCI113181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Weetman A. P., McGregor A. M. Autoimmune thyroid disease: developments in our understanding. Endocr Rev. 1984 Spring;5(2):309–355. doi: 10.1210/edrv-5-2-309. [DOI] [PubMed] [Google Scholar]
  20. Weetman A. P., Rennie D. P., Hassman R., Hall R., McGregor A. M. Enzyme-linked immunoassay of monoclonal and serum microsomal autoantibodies. Clin Chim Acta. 1984 Apr 27;138(3):237–244. doi: 10.1016/0009-8981(84)90130-x. [DOI] [PubMed] [Google Scholar]
  21. Weil S. C., Rosner G. L., Reid M. S., Chisholm R. L., Farber N. M., Spitznagel J. K., Swanson M. S. cDNA cloning of human myeloperoxidase: decrease in myeloperoxidase mRNA upon induction of HL-60 cells. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2057–2061. doi: 10.1073/pnas.84.7.2057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Weitzman S. A., Stossel T. P., Harmon D. C., Daniels G., Maloof F., Ridgway E. C. Antineutrophil autoantibodies in Graves' disease. Implications of thyrotropin binding to neutrophils. J Clin Invest. 1985 Jan;75(1):119–123. doi: 10.1172/JCI111663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Welinder K. G. Covalent structure of the glycoprotein horseradish peroxidase (EC 1.11.1.7). FEBS Lett. 1976 Dec 15;72(1):19–23. doi: 10.1016/0014-5793(76)80804-6. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES