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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.
Department of Medicine, Nepean Hospital, University of Sydney, Penrith, NSW, 2751, Australia.
This article was published in the following journal.
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Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
Antibodies produced by human or animal cells following clinical or experimental exposure to parasitic HELMINTH ANTIGENS. The IMMUNOGLOBULIN E class of immunoglobulins is usually formed and released, but IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; and IMMUNOGLOBULIN A may also occur.
Heavy chains of IMMUNOGLOBULIN G having a molecular weight of approximately 51 kDa. They contain about 450 amino acid residues arranged in four domains and an oligosaccharide component covalently bound to the Fc fragment constant region. The gamma heavy chain subclasses (for example, gamma 1, gamma 2a, and gamma 2b) of the IMMUNOGLOBULIN G isotype subclasses (IgG1, IgG2A, and IgG2B) resemble each other more closely than the heavy chains of the other IMMUNOGLOBULIN ISOTYPES.
A site located in the INTRONS at the 5' end of each constant region segment of a immunoglobulin heavy-chain gene where recombination (or rearrangement) occur during IMMUNOGLOBULIN CLASS SWITCHING. Ig switch regions are found on genes encoding all five classes (IMMUNOGLOBULIN ISOTYPES) of IMMUNOGLOBULIN HEAVY CHAINS.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
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