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. 1990 Sep;86(3):723–727. doi: 10.1172/JCI114768

Thyroid-stimulating antibody activity between different immunoglobulin G subclasses.

A P Weetman 1, M E Yateman 1, P A Ealey 1, C M Black 1, C B Reimer 1, R C Williams Jr 1, B Shine 1, N J Marshall 1
PMCID: PMC296786  PMID: 2168443

Abstract

To investigate the distribution of thyroid-stimulating antibody (TSAb) activity between IgG subclasses, sera from 11 patients with Graves disease (including the National Institute of Biological Standards and Control (NIBSC) Research Standard, long acting thyroid stimulator-B) were fractionated by chromatography on affinity columns of monoclonal IgG subclass antibodies or protein A to deplete all but a single subclass. The resulting fractions were 98% or more pure for a single subclass. In all 11 patients, TSAb activity appeared to be confined to the IgG1 fraction as determined by cAMP production on addition of the fractions to the FRTL-5 rat thyroid cell line. In all of eight specimens from seven patients so tested, the whole serum activity was recovered in the IgG1 fraction, after adjusting for the recovery of the isotype from the column. TSAb activity in one serum comprised both lambda and kappa light chains but was IgG1 restricted. This IgG subclass restriction was not found when the same fractions were tested for thyroglobulin, microsomal/thyroid peroxidase, or tetanus toxoid antibody activity. Together with previous results showing marked restriction of both light chain usage and isoelectric point of TSAb, these results support the idea that Graves' disease may be the result of an oligo- or possibly monoclonal response at the B cell level.

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Selected References

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  1. Black C. M., Plikaytis B. D., Wells T. W., Ramirez R. M., Carlone G. M., Chilmonczyk B. A., Reimer C. B. Two-site immunoenzymometric assays for serum IgG subclass infant/maternal ratios at full-term. J Immunol Methods. 1988 Jan 21;106(1):71–81. doi: 10.1016/0022-1759(88)90273-6. [DOI] [PubMed] [Google Scholar]
  2. Burman K. D., Baker J. R., Jr Immune mechanisms in Graves' disease. Endocr Rev. 1985 Spring;6(2):183–232. doi: 10.1210/edrv-6-2-183. [DOI] [PubMed] [Google Scholar]
  3. Burton D. R., Gregory L., Jefferis R. Aspects of the molecular structure of IgG subclasses. Monogr Allergy. 1986;19:7–35. [PubMed] [Google Scholar]
  4. Davies T. F., Weber C. M., Wallack P., Platzer M. Restricted heterogeneity and T cell dependence of human thyroid autoantibody immunoglobulin G subclasses. J Clin Endocrinol Metab. 1986 May;62(5):945–949. doi: 10.1210/jcem-62-5-945. [DOI] [PubMed] [Google Scholar]
  5. Jefferis R., Reimer C. B., Skvaril F., de Lange G., Ling N. R., Lowe J., Walker M. R., Phillips D. J., Aloisio C. H., Wells T. W. Evaluation of monoclonal antibodies having specificity for human IgG sub-classes: results of an IUIS/WHO collaborative study. Immunol Lett. 1985;10(3-4):223–252. doi: 10.1016/0165-2478(85)90082-3. [DOI] [PubMed] [Google Scholar]
  6. Knight J., Laing P., Knight A., Adams D., Ling N. Thyroid-stimulating autoantibodies usually contain only lambda-light chains: evidence for the "forbidden clone" theory. J Clin Endocrinol Metab. 1986 Feb;62(2):342–347. doi: 10.1210/jcem-62-2-342. [DOI] [PubMed] [Google Scholar]
  7. Lundgren M., Persson U., Larsson P., Magnusson C., Smith C. I., Hammarström L., Severinson E. Interleukin 4 induces synthesis of IgE and IgG4 in human B cells. Eur J Immunol. 1989 Jul;19(7):1311–1315. doi: 10.1002/eji.1830190724. [DOI] [PubMed] [Google Scholar]
  8. MEEK J. C., JONES A. E., LEWIS U. J., VANDERLAAN W. P. CHARACTERIZATION OF THE LONG-ACTING THYROID STIMULATOR OF GRAVES' DISEASE. Proc Natl Acad Sci U S A. 1964 Aug;52:342–349. doi: 10.1073/pnas.52.2.342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Manley S. W., Knight A., Adams D. D. The thyrotrophin receptor. Springer Semin Immunopathol. 1982;5(4):413–431. doi: 10.1007/BF01857428. [DOI] [PubMed] [Google Scholar]
  10. McKenzie J. M., Zakarija M. LATS in Graves' disease. Recent Prog Horm Res. 1976;33:29–57. doi: 10.1016/b978-0-12-571133-3.50009-x. [DOI] [PubMed] [Google Scholar]
  11. McLachlan S. M., Pegg C. A., Atherton M. C., Middleton S. L., Clark F., Rees Smith B. TSH receptor antibody synthesis by thyroid lymphocytes. Clin Endocrinol (Oxf) 1986 Feb;24(2):223–230. doi: 10.1111/j.1365-2265.1986.tb00766.x. [DOI] [PubMed] [Google Scholar]
  12. Morgan B. P., Daniels R. H., Watts M. J., Williams B. D. In vivo and in vitro evidence of cell recovery from complement attack in rheumatoid synovium. Clin Exp Immunol. 1988 Sep;73(3):467–472. [PMC free article] [PubMed] [Google Scholar]
  13. Ochi Y., Yoshimura M., Hachiya T., Miyazaki T. Distribution of LATS activity in immunoglobulin G subclass. Acta Endocrinol (Copenh) 1977 Aug;85(4):791–798. doi: 10.1530/acta.0.0850791. [DOI] [PubMed] [Google Scholar]
  14. Parkes A. B., McLachlan S. M., Bird P., Rees Smith B. The distribution of microsomal and thyroglobulin antibody activity among the IgG subclasses. Clin Exp Immunol. 1984 Jul;57(1):239–243. [PMC free article] [PubMed] [Google Scholar]
  15. Persson M. A. Preparation of human sera containing one single IgG subclass using affinity chromatography. J Immunol Methods. 1987 Apr 2;98(1):91–98. doi: 10.1016/0022-1759(87)90440-6. [DOI] [PubMed] [Google Scholar]
  16. Rees Smith B., McLachlan S. M., Furmaniak J. Autoantibodies to the thyrotropin receptor. Endocr Rev. 1988 Feb;9(1):106–121. doi: 10.1210/edrv-9-1-106. [DOI] [PubMed] [Google Scholar]
  17. Spiegelberg H. L. Biological activities of immunoglobulins of different classes and subclasses. Adv Immunol. 1974;19(0):259–294. doi: 10.1016/s0065-2776(08)60254-0. [DOI] [PubMed] [Google Scholar]
  18. Stevens T. L., Bossie A., Sanders V. M., Fernandez-Botran R., Coffman R. L., Mosmann T. R., Vitetta E. S. Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells. Nature. 1988 Jul 21;334(6179):255–258. doi: 10.1038/334255a0. [DOI] [PubMed] [Google Scholar]
  19. Weetman A. P., Black C. M., Cohen S. B., Tomlinson R., Banga J. P., Reimer C. B. Affinity purification of IgG subclasses and the distribution of thyroid auto-antibody reactivity in Hashimoto's thyroiditis. Scand J Immunol. 1989 Jul;30(1):73–82. doi: 10.1111/j.1365-3083.1989.tb01190.x. [DOI] [PubMed] [Google Scholar]
  20. Weetman A. P., Cohen S. B., Oleesky D. A., Morgan B. P. Terminal complement complexes and C1/C1 inhibitor complexes in autoimmune thyroid disease. Clin Exp Immunol. 1989 Jul;77(1):25–30. [PMC free article] [PubMed] [Google Scholar]
  21. Weetman A. P., Cohen S. The IgG subclass distribution of thyroid autoantibodies. Immunol Lett. 1986 Nov 3;13(6):335–341. doi: 10.1016/0165-2478(86)90068-4. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Weetman A. P., McGregor A. M., Lazarus J. H., Hall R. Thyroid antibodies are produced by thyroid-derived lymphocytes. Clin Exp Immunol. 1982 Apr;48(1):196–200. [PMC free article] [PubMed] [Google Scholar]
  24. Williams R. C., Jr, Marshall N. J., Kilpatrick K., Montano J., Brickell P. M., Goodall M., Ealey P. A., Shine B., Weetman A. P., Craig R. K. Kappa/lambda immunoglobulin distribution in Graves' thyroid-stimulating antibodies. Simultaneous analysis of C lambda gene polymorphisms. J Clin Invest. 1988 Oct;82(4):1306–1312. doi: 10.1172/JCI113731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Witte A., Akyol B., Hörterer L., Pickardt C. R. Further characterization of thyrotropin-displacing-activity (TDA): evidence of restricted heterogeneity. Horm Metab Res. 1986 Dec;18(12):858–861. doi: 10.1055/s-2007-1012456. [DOI] [PubMed] [Google Scholar]
  26. Zakarija M. Immunochemical characterization of the thyroid-stimulating antibody (TSAb) of Graves' disease: evidence for restricted heterogeneity. J Clin Lab Immunol. 1983 Feb;10(2):77–85. [PubMed] [Google Scholar]
  27. Zakarija M., McKenzie J. M. Isoelectric focusing of thyroid-stimulating antibody of Graves' disease. Endocrinology. 1978 Oct;103(4):1469–1475. doi: 10.1210/endo-103-4-1469. [DOI] [PubMed] [Google Scholar]

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