Tryptic peptides of human thyroglobulin: II. Immunoreactivity with sera from patients with thyroid diseases.
Tryptic peptides of human thyroglobulin (Tg) were analysed by Western immunoblot for their reactivity to circulating autoantibodies from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD) and thyroid carcinoma, and from normal human controls. Low molecular weight peptides were released after 4 h incubation of Tg with trypsin. The sera of thyroid disease patients reacted with several peptides, but predominantly bound three peptides with apparent molecular weights (MWap) of 25 kD, 20 kD, and 15 kD; the sera of normal individuals did not bind these fragments of Tg. The pattern of tryptic peptides recognized by the majority of sera from GD patients differed from that recognized by sera from most patients with HT. Autoantibodies from both groups of patients recognized a 15-kD peptide with a high frequency, but the sera from 26/43 (60%) GD patients also recognized a peptide with MWap of 25 kD, whereas the sera from 22/35 (63%) of HT patients recognized a 20-kD peptide. A few sera from patients with thyroid carcinoma reacted with peptides with MWap of 15 and 20-kD, and none bound the 25-kD peptide. The immunoreactivity of autoantibodies in HT sera to the 20-kD peptide paralleled the competitive inhibition of the MoAb 137C1 by these sera. In addition, MoAb 137C1 and Hashimoto's sera showed the same Western immunoblot-binding pattern to Tg tryptic peptides, suggesting that a Hashimoto-associated epitope and the 137C1-binding site are found on the same peptide. These findings suggest that distinct peptides are recognized by Tg autoantibodies from patients with different thyroid diseases.
Saboori
A M
AM
Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205.
Caturegli
P
P
Rose
N R
NR
Mariotti
S
S
Pinchera
A
A
Burek
C L
CL
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology; D001667:Binding, Competitive; D000939:Epitopes / Q000276:immunology; D006111:Graves Disease / Q000097:blood / Q000276:immunology*; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D012016:Reference Values; D013954:Thyroglobulin / Q000276:immunology* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000097:blood / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000097:blood / Q000276:immunology*; D014357:Trypsin / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D010446:Peptide Fragments; D013954:Thyroglobulin; D014357:Trypsin