Thyroid peroxidase and thyroid microsomal autoantibodies.
The antithyroid microsomal antibodies found in the serum of patients with autoimmune thyroid disease are directed largely, if not entirely, against thyroid peroxidase (TPO). In this study we used a highly purified, well characterized, large tryptic fragment of porcine TPO (hereafter referred to as purified porcine TPO) to examine possible differences among microsomal antibodies in patients with autoimmune thyroid disease. Antibodies against this TPO preparation and also against a synthetic peptide corresponding to residues 780-793 of the deduced sequence of the native enzyme were compared with microsomal antibodies from patients in immunoblot experiments. The antiporcine TPO and antisynthetic peptide antibodies reacted with crude preparations of human TPO. Binding of serum microsomal antibodies to purified porcine TPO was also found. Purified porcine TPO shows two fragments after gel electrophoresis under reducing conditions: a 59K fragment corresponding to the amino end of the molecule, and two approximately 30K fragments corresponding to the carboxyl end. Using an immunoblot procedure with purified porcine TPO as the antigen, we found that at least two epitopes were involved in microsomal antibody production: one associated with the 59K fragment and the other with the approximately 30K fragment(s). The distribution of serum antibodies against these epitopes differed among the patients, indicating that these antibodies comprise a heterogeneous group. Serum from patients with autoimmune thyroid disease significantly inhibited human TPO activity, raising the possibility that microsomal antibodies may contribute to the impaired thyroid function that occurs in some patients with autoimmune thyroid disease.
Yokoyama
N
N
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235.
Taurog
A
A
Klee
G G
GG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D002648:Child; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D015151:Immunoblotting; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors / Q000276:immunology*; D033862:Iron-Binding Proteins; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D011817:Rabbits; D013552:Swine; D013967:Thyroiditis, Autoimmune / Q000201:enzymology* / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D007106:Immune Sera; D033862:Iron-Binding Proteins; D010446:Peptide Fragments; C056626:thyroid microsomal antibodies; C056658:TPO protein, human; D007453:Iodide Peroxidase