Isotype and immunoglobulin subclass distribution of Eye muscle membrane reactive antibodies in the serum of patients with thyroid-associated ophthalmopathy as detected in western blotting

N. F. Bernard, F. Ertug, N. Teboul, Z. G. Zhang, M. Salvi, J. R. Wall

Research output: Contribution to journalArticle

Abstract

We have determined the immunoglobulin (Ig) class (isotype) and IgG subclass of autoantibodies in the serum of patients with thyroid-associated ophthalmopathy (TAO) or autoimmune thyroid disorders without evident ophthalmopathy reactive in Western blotting with antigens of 55, 64, 75 and 95 kDa in pig eye muscle membrane (PEMM). The 22 sera studied were shown, previously, to contain IgG antibodies reactive with one or more of the four antigens. The majority of sera antibodies reactive with PEMM antigens were of two or more IgG subclasses. of the IgG subclass specificities IgG1 and IgG2 subclass antibodies were, overall, the most common. We were unable to demonstrate IgG subclass restriction for antibodies reactive with the 95 or 55 kDa antigens in PEMM, antibody activity being equally distributed in all four subclasses tested. While most of the sera which recognized a 64 kDa antigen did so with an IgG4 antibody, all other subclasses were also represented. on the other hand all 13 sera reactive with a 75 kDa antigen did so using Ig of the IgG, subclass and 12 of these used the IgG, subclass as well, IgG, and IgG, subclasses being represented in only 3 and 4 sera, respectively. There were no differences, in respect to Ig class or IgG subclass distribution of eye muscle reactive antibodies between patients with Graves' hyperthyroidism with ophthalmopathy and those with Hashimoto's thyroiditis, and eye disease. Control sera from five normal subjects and three patients with non-autoimmune thyroid disorders did not contain antibodies reactive with these PEMM antigens of any Ig class or IgG subclass. IgG3 and IgG1 antibodies fix complement and can mediate cytotoxicity, while those of the IgG4 subclass do not. Antibodies to eye muscle membrane antigens thus have the potential to mediate cytotoxic damage of eye muscle cells, which is consistent with the hypothesis that one or more of these antibodies may be pathogenic in TAO.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalAutoimmunity
Volume10
Issue number1
DOIs
Publication statusPublished - 1991

Keywords

  • 64 kDa protein
  • Cytotoxicity
  • Eye muscle antibodies
  • Thyroid-associated ophthalmopathy
  • Western blotting

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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