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.