T-cell recognition of residue 158-176 in thyrotropin receptor confers risk for development of thyroid autoimmunity in siblings in a family with Graves' disease.
Twenty-two subjects in a family with Graves' Disease and 20 normal subjects unrelated to the family were examined for T-cell responses to rec h TSHR-ECD and its synthetic peptides. Seven of the family members and none of the controls responded positively to rec h TSHR-ECD. Peptide 158-176 was the only residue that showed a high percentage of response among family members, no responses in spouses, and a significant difference compared to unrelated controls. Family members under age of 6 did not differ from spouses in response to rec h TSHR-ECD or any individual peptide. Family members ages 6-12 years were significantly different from spouses in response to peptides 30-49, 158-176, and 172-186. The reactivity of adult family members including 3 Graves' patients was significantly different from spouses in response to peptides 44-62, 132-150, 158-176, and 248-263. The responses of female members of the family were higher than that of the male members and significantly different for peptide 272-291. These data suggest that recognition of peptide 158-176 may be an early event in the pathogenesis of the disease and that recognition of both 158-176 and 248-263 residues may be the cornerstone for establishment of the disease.
Soliman
M
M
Department of Medicine, The University of Chicago, Illinois 60637, USA.
Kaplan
E
E
Guimaraes
V
V
Yanagawa
T
T
DeGroot
L J
LJ
D000293:Adolescent; D000328:Adult; D015551:Autoimmunity; D002648:Child; D002675:Child, Preschool; D000939:Epitopes / Q000276:immunology; D005260:Female; D006111:Graves Disease / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010446:Peptide Fragments / Q000276:immunology*; D011989:Receptors, Thyrotropin / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013961:Thyroid Gland / Q000276:immunology*
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D011989:Receptors, Thyrotropin; D011994:Recombinant Proteins