Epitopes, immunoglobulin classes and immunoglobulin G subclasses of calsequestrin antibodies in patients with thyroid eye disease

Abstract

A number of serum autoantibodies are associated with thyroid eye disease (TED), including those reactive against the calcium binding protein calsequestrin (CASQ). There are two isoforms of CASQ namely; CASQ1, found in skeletal, including extra ocular, muscle, and CASQ2, found in cardiac muscle. We determined (i) the reactivity profiles of CASQ1 and CASQ2 antibodies and (ii) the immunoglobulin (Ig) classes and IgG subclasses of CASQ1 antibodies, using enzyme-linked immunosorbent assay. Of the 20 patients with TED tested, 35% were positive for CASQ1 antibodies, 25% for CASQ2 antibodies and two patients (10%) were positive for both antibodies. Of the 12 patients with Hashimoto's thyroiditis and ophthalmopathy tested, 25% were positive for CASQ1 antibodies, 42% for CASQ2 antibodies and two patients (17%) were positive for both antibodies. CASQ1 antibodies were mainly of the IgG class and IgG1 and IgG3 subclasses. These results suggest that CASQ1 and CASQ2 do not share major epitopes. Because antibodies of the IgG1 and IgG3 subclasses are cytotoxic, CASQ1 antibodies may contribute to the eye muscle damage in patients with TED. Because CASQ1 antibodies were positive in only a third of patients with active TED we are unable to draw conclusions about their role in its pathogenesis. On the other hand, a possible role of CASQ2 antibodies in the aetiology of the cardiac complications of Graves' disease is a new avenue for research and appears worthy of further investigation.

Keywords::

• Graves' disease, thyroid eye disease, calsequestrin, autoimmunity, eye muscle

Acknowledgements

This research was supported by grants from Sydney West Area Health Service (Nepean Hospital), the Nepean Medical Research Foundation and Bekker La Bastide Fonds, Fundatie van Vrijvrouwe van Renswoude, Beuningen van Helsdingen fonds and Spinozafonds (The Netherlands). We thank Dr Nicole Beard (The John Curtin School of Medical Research, ACT Australia) for supplying rabbit skeletal muscle calsequestrin and purified cardiac muscle calsequestrin.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.