Detection of the novel autoantibody (anti-UACA antibody) in patients with Graves’ disease

doi:10.1016/j.bbrc.2004.06.162

Biochemical and Biophysical Research Communications

Volume 321, Issue 2, 20 August 2004, Pages 432-440

https://doi.org/10.1016/j.bbrc.2004.06.162 Get rights and content

Abstract

Uveal autoantigen with coiled coil domains and ankyrin repeats (UACA) is an autoantigen in patients with panuveitis such as Vogt–Koyanagi–Harada disease. The prevalence of IgG anti-UACA antibodies in patients with uveitis is significantly higher than healthy controls, suggesting its potential role as an autoantigen. Originally, UACA was cloned from dog thyroid tissue following TSH stimulation. So, we presumed UACA could be a novel autoantigen in autoimmune thyroid diseases. We measured serum anti-UACA antibody titer using ELISA in patients with autoimmune thyroid diseases (Graves’ disease, Hashimoto’s thyroiditis, subacute thyroiditis, and silent thyroiditis). The prevalence of anti-UACA antibodies in Graves’ disease group was significantly higher than that in healthy group (15% vs. 0%). Moreover, the prevalence of anti-UACA antibodies in Graves’ ophthalmopathy was significantly higher than that in Graves’ patients without ophthalmopathy (29% vs. 11%). Especially, 75% of severe ocular myopathy cases showed high UACA titer. Immunohistochemical analysis revealed that UACA protein is expressed in eye muscles as well as human thyroid follicular cells. Taken together, UACA is a novel candidate for eye muscle autoantigens in thyroid-associated ophthalmopathy.

Section snippets

Materials and methods

Study patients. We studied 159 Graves’ disease, 26 Hashimoto’s thyroiditis, 20 silent thyroiditis, 11 subacute thyroiditis, and 43 controls. We explained the purpose of this study to all subjects and obtained their informed consent. Graves’ disease patients consisted of untreated 122 females and 37 males. Diagnosis of Graves’ disease was confirmed by elevated free T₃ level (13.61 ± 6.67 ng/dl), undetectable TSH level, and positive TSH binding inhibitory immunoglobulin and/or thyroid stimulating

ELISA

We measured serum UACA antibody titer in patients with autoimmune thyroid diseases in ELISA, using recombinant C-terminal 18% fragment of human UACA protein. We measured titer of healthy controls (43 cases), Graves’ disease (159 cases), Hashimoto’s disease (26 cases), silent thyroiditis (20 cases), and subacute thyroiditis (11 cases). To exclude the effect of reactivity against GST protein, we used GST–UACA fusion protein and GST protein for ELISA, simultaneously. Evaluation of IgG anti-UACA

Discussion

UACA is a protein cloned by serological analysis of recombinant cDNA expression libraries (SEREX) method with serum samples obtained from patients with VKH disease, to identify the target autoantigens in VKH disease [1]. VKH disease is recognized as an autoimmune systemic disorder. In VKH, inflammatory disorders in multiple organs include melanocytes, uvea (resulting in acute bilateral panuveitis), skin (vitiligo and alopecia), central nervous system (meningitis), and inner ears (hearing loss

Acknowledgments

We appreciate Prof. Ito H (Division of Organ Pathology, Department of Microbiology and Pathology, Tottori University Faculty of Medicine, Yonago 683-8504, Japan) and Prof. Watanabe T (Division of Integrative physiology, Department of Functional, Morphological and Regulation Science, Tottori University Faculty of Medicine, Yonago 683-8504, Japan) for their kind technical advices and generous suggestions. We also appreciate TRANS GENIC INC. (Kumamoto 861-2202, Japan) for the production and kind

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Detection of the novel autoantibody (anti-UACA antibody) in patients with Graves’ disease

Abstract

Section snippets

Materials and methods

ELISA

Discussion

Acknowledgments

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Lancet

Immunol. Today

FEBS Lett.

Clin. Immunol. Immunopathol.

Biochem. Biophys. Res. Commun.

The ocular muscle cell is a target of the immune system in endocrine ophthalmopathy

Proc. Int. Arch. Allergy. Immunol.

Thyroid-associated eye disease: pathophysiology

Lancet

Graves’ ophthalmopathy: current concepts regarding pathogenesis and management

Endocrinol. Rev.

Importance of TSH receptor activation in the development of severe endocrine ophthalmopathy

Acta Endocrinol.

Thyrotropin receptor expression in Graves’ orbital adipose/connective tissues: potential autoantigen in Graves’ ophthalmopathy

J. Clin. Endocrinol. Metab.

Presence of nonfunctional thyrotropin receptor variant transcripts in retroocular and other tissues

J. Clin. Endocrinol. Metab.

Pathophysiology of Graves’ ophthalmopathy: the cycle of disease

J. Clin. Endocrinol. Metab.

Significance of anti-eye muscle antibody in patients with thyroid-associated ophthalmopathy by quantitative Western blot

Autoimmunity