Study of serum antibodies against three eye muscle antigens and the connective tissue antigen collagen XIII in patients with Graves' disease with and without ophthalmopathy: correlation with clinical features

Bamini Gopinath, Reilly Musselman, Cherie-Lee Adams, Junichi Tani, Nicole Beard, Jack R Wall

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

OBJECTIVE: The extraocular muscles are one of the primary tissues implicated in the autoimmune-mediated inflammation of thyroid-associated ophthalmopathy (TAO). Our aim was to determine the prevalence and level of antibodies against three candidate eye muscle antigens and the orbital fibroblast membrane antigen collagen XIII, in well-characterized patient groups.

STUDY DESIGN AND PATIENTS: The study cohort consisted of patients with Graves' hyperthyroidism with and without ophthalmopathy, controls patients with other thyroid or other autoimmune disorders and healthy subjects. The presence of eye muscle antibodies was determined using an optimized and standardized enzyme-linked immunosorbent assay. We measured antibodies against (i) the 67-kDa flavoprotein (Fp) subunit of the mitochondrial enzyme succinate dehydrogenase; (ii) G2s, a 141 amino acid fragment of the winged-helix transcription factor FOXP1; (iii) calsequestrin, a 63-kDa calcium-binding protein; and (iv) collagen XIII, a connective tissue protein that is closely linked to the congestive ophthalmopathy subtype of TAO. Eye muscle antibody levels were correlated with clinical diagnosis and presence or not of ophthalmopathy.

RESULTS: Prevalences of positive antibody tests to calsequestrin (75.0%) and collagen XIII (43.8%) were significantly greater in Graves' disease (GD) patients with ophthalmopathy than in healthy subjects, whereas modest significance was demonstrated with antibodies against Fp, but not G2s. Significantly greater serum levels of antibodies against calsequestrin, G2s, and collagen XIII, but not Fp, were found in GD patients with ophthalmopathy compared to control patients without eye disease and healthy subjects.

CONCLUSIONS: Calsequestrin and collagen XIII antibodies are the most specific to TAO, whereas antibodies against G2s, and to a lesser extent Fp, are also markers of ophthalmopathy, but less reliable. These results are unique in that it is the first time the significance of a panel of three candidate eye muscle antibodies and a connective tissue antibody have been evaluated in the same patients with ophthalmopathy.

Original languageEnglish
Pages (from-to)967-974
Number of pages8
JournalThyroid
Volume16
Issue number10
DOIs
Publication statusPublished - 16 Oct 2006
Externally publishedYes

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Graves Disease
Connective Tissue
Collagen
Antigens
Muscles
Antibodies
Calsequestrin
Serum
Graves Ophthalmopathy
Flavoproteins
Healthy Volunteers
Oculomotor Muscles
Winged-Helix Transcription Factors
Calcium-Binding Proteins
Succinate Dehydrogenase
Eye Diseases
Hyperthyroidism
Thyroid Gland
Cohort Studies
Fibroblasts

Cite this

@article{98be3c69e5744aa5a2b0c216be0e0849,
title = "Study of serum antibodies against three eye muscle antigens and the connective tissue antigen collagen XIII in patients with Graves' disease with and without ophthalmopathy: correlation with clinical features",
abstract = "OBJECTIVE: The extraocular muscles are one of the primary tissues implicated in the autoimmune-mediated inflammation of thyroid-associated ophthalmopathy (TAO). Our aim was to determine the prevalence and level of antibodies against three candidate eye muscle antigens and the orbital fibroblast membrane antigen collagen XIII, in well-characterized patient groups.STUDY DESIGN AND PATIENTS: The study cohort consisted of patients with Graves' hyperthyroidism with and without ophthalmopathy, controls patients with other thyroid or other autoimmune disorders and healthy subjects. The presence of eye muscle antibodies was determined using an optimized and standardized enzyme-linked immunosorbent assay. We measured antibodies against (i) the 67-kDa flavoprotein (Fp) subunit of the mitochondrial enzyme succinate dehydrogenase; (ii) G2s, a 141 amino acid fragment of the winged-helix transcription factor FOXP1; (iii) calsequestrin, a 63-kDa calcium-binding protein; and (iv) collagen XIII, a connective tissue protein that is closely linked to the congestive ophthalmopathy subtype of TAO. Eye muscle antibody levels were correlated with clinical diagnosis and presence or not of ophthalmopathy.RESULTS: Prevalences of positive antibody tests to calsequestrin (75.0{\%}) and collagen XIII (43.8{\%}) were significantly greater in Graves' disease (GD) patients with ophthalmopathy than in healthy subjects, whereas modest significance was demonstrated with antibodies against Fp, but not G2s. Significantly greater serum levels of antibodies against calsequestrin, G2s, and collagen XIII, but not Fp, were found in GD patients with ophthalmopathy compared to control patients without eye disease and healthy subjects.CONCLUSIONS: Calsequestrin and collagen XIII antibodies are the most specific to TAO, whereas antibodies against G2s, and to a lesser extent Fp, are also markers of ophthalmopathy, but less reliable. These results are unique in that it is the first time the significance of a panel of three candidate eye muscle antibodies and a connective tissue antibody have been evaluated in the same patients with ophthalmopathy.",
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Study of serum antibodies against three eye muscle antigens and the connective tissue antigen collagen XIII in patients with Graves' disease with and without ophthalmopathy: correlation with clinical features. / Gopinath, Bamini; Musselman, Reilly; Adams, Cherie-Lee; Tani, Junichi; Beard, Nicole; Wall, Jack R.

In: Thyroid, Vol. 16, No. 10, 16.10.2006, p. 967-974.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Study of serum antibodies against three eye muscle antigens and the connective tissue antigen collagen XIII in patients with Graves' disease with and without ophthalmopathy: correlation with clinical features

AU - Gopinath, Bamini

AU - Musselman, Reilly

AU - Adams, Cherie-Lee

AU - Tani, Junichi

AU - Beard, Nicole

AU - Wall, Jack R

PY - 2006/10/16

Y1 - 2006/10/16

N2 - OBJECTIVE: The extraocular muscles are one of the primary tissues implicated in the autoimmune-mediated inflammation of thyroid-associated ophthalmopathy (TAO). Our aim was to determine the prevalence and level of antibodies against three candidate eye muscle antigens and the orbital fibroblast membrane antigen collagen XIII, in well-characterized patient groups.STUDY DESIGN AND PATIENTS: The study cohort consisted of patients with Graves' hyperthyroidism with and without ophthalmopathy, controls patients with other thyroid or other autoimmune disorders and healthy subjects. The presence of eye muscle antibodies was determined using an optimized and standardized enzyme-linked immunosorbent assay. We measured antibodies against (i) the 67-kDa flavoprotein (Fp) subunit of the mitochondrial enzyme succinate dehydrogenase; (ii) G2s, a 141 amino acid fragment of the winged-helix transcription factor FOXP1; (iii) calsequestrin, a 63-kDa calcium-binding protein; and (iv) collagen XIII, a connective tissue protein that is closely linked to the congestive ophthalmopathy subtype of TAO. Eye muscle antibody levels were correlated with clinical diagnosis and presence or not of ophthalmopathy.RESULTS: Prevalences of positive antibody tests to calsequestrin (75.0%) and collagen XIII (43.8%) were significantly greater in Graves' disease (GD) patients with ophthalmopathy than in healthy subjects, whereas modest significance was demonstrated with antibodies against Fp, but not G2s. Significantly greater serum levels of antibodies against calsequestrin, G2s, and collagen XIII, but not Fp, were found in GD patients with ophthalmopathy compared to control patients without eye disease and healthy subjects.CONCLUSIONS: Calsequestrin and collagen XIII antibodies are the most specific to TAO, whereas antibodies against G2s, and to a lesser extent Fp, are also markers of ophthalmopathy, but less reliable. These results are unique in that it is the first time the significance of a panel of three candidate eye muscle antibodies and a connective tissue antibody have been evaluated in the same patients with ophthalmopathy.

AB - OBJECTIVE: The extraocular muscles are one of the primary tissues implicated in the autoimmune-mediated inflammation of thyroid-associated ophthalmopathy (TAO). Our aim was to determine the prevalence and level of antibodies against three candidate eye muscle antigens and the orbital fibroblast membrane antigen collagen XIII, in well-characterized patient groups.STUDY DESIGN AND PATIENTS: The study cohort consisted of patients with Graves' hyperthyroidism with and without ophthalmopathy, controls patients with other thyroid or other autoimmune disorders and healthy subjects. The presence of eye muscle antibodies was determined using an optimized and standardized enzyme-linked immunosorbent assay. We measured antibodies against (i) the 67-kDa flavoprotein (Fp) subunit of the mitochondrial enzyme succinate dehydrogenase; (ii) G2s, a 141 amino acid fragment of the winged-helix transcription factor FOXP1; (iii) calsequestrin, a 63-kDa calcium-binding protein; and (iv) collagen XIII, a connective tissue protein that is closely linked to the congestive ophthalmopathy subtype of TAO. Eye muscle antibody levels were correlated with clinical diagnosis and presence or not of ophthalmopathy.RESULTS: Prevalences of positive antibody tests to calsequestrin (75.0%) and collagen XIII (43.8%) were significantly greater in Graves' disease (GD) patients with ophthalmopathy than in healthy subjects, whereas modest significance was demonstrated with antibodies against Fp, but not G2s. Significantly greater serum levels of antibodies against calsequestrin, G2s, and collagen XIII, but not Fp, were found in GD patients with ophthalmopathy compared to control patients without eye disease and healthy subjects.CONCLUSIONS: Calsequestrin and collagen XIII antibodies are the most specific to TAO, whereas antibodies against G2s, and to a lesser extent Fp, are also markers of ophthalmopathy, but less reliable. These results are unique in that it is the first time the significance of a panel of three candidate eye muscle antibodies and a connective tissue antibody have been evaluated in the same patients with ophthalmopathy.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Autoantibodies

KW - Calsequestrin

KW - Cell Cycle Proteins

KW - Collagen

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Flavoproteins

KW - Graves Disease

KW - Graves Ophthalmopathy

KW - Humans

KW - Male

KW - Middle Aged

KW - Oculomotor Muscles

KW - Receptors, G-Protein-Coupled

KW - Reference Values

KW - Thyroxine

U2 - 10.1089/thy.2006.16.967

DO - 10.1089/thy.2006.16.967

M3 - Article

VL - 16

SP - 967

EP - 974

JO - Thyroid

JF - Thyroid

SN - 1050-7256

IS - 10

ER -