title: 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.
authors.affiliation: Department of Medicine, Nepean Hospital, University of Sydney, Penrith, NSW, 2751, Australia.
authors.forename: Sofie
authors.initials: S
authors.lastname: de Haan
authors.forename: Hooshang
authors.initials: H
authors.lastname: Lahooti
authors.forename: Olivia
authors.initials: O
authors.lastname: Morris
authors.forename: Jack R
authors.initials: JR
authors.lastname: Wall
mesh_terms: D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins / Q000276:immunology*; D002155:Calsequestrin / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D049970:Graves Ophthalmopathy / Q000276:immunology*; D050031:Hashimoto Disease / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000276:immunology*
chemical_list: C503129:CASQ1 protein, human; C443109:CASQ2 protein, human; D002135:Calcium-Binding Proteins; D002155:Calsequestrin; D000939:Epitopes; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D024101:Mitochondrial Proteins