Detection and characterization of autoantibodies blocking the TSH-dependent cAMP production using FRTL-5 cells.
Autoantibodies blocking the TSH-stimulated cAMP production (TBkAb) were measured in immunoglobulin G (IgG) preparations from 38 patients with primary autoimmune hypothyroidism, using FRTL-5 cells. TBkAb were detectable in 15/23 IgG preparations from patients with untreated idiopathic myxedema, and in 2/15 IgGs from patients under L-thyroxine treatment. None of the IgG from 22 normal subjects or from 10 patients with nonautoimmune hypothyroidism following total thyroidectomy caused any significant effect on the TSH-stimulated cAMP production. No correlation was found between TBkAb and the thyroid microsomal antibody. Antibodies inhibiting the 125I-TSH binding to TSH receptor were detectable in only 3/20 patients; IgGs from these 3 patients were also positive in the TBkAb assay. One IgG with potent TBkAb activity inhibited the TSH-stimulated adenylate cyclase in a competitive manner, while it had no effect on the forskolin-stimulated cAMP production. The inhibiting action of this IgG was almost completely lost after preabsorption with human thyroid membranes. In conclusion, we describe a new practical and sensitive method for the measurement of TBkAb; TBkAb are distinct from the microsomal antibody, and are probably directed to the TSH receptor.
Chiovato
L
L
Istituto di Metodologia Clinica, University of Pisa, Tirrenia, Italy.
Vitti
P
P
Lombardi
A
A
Lopez
G
G
Santini
F
F
Macchia
E
E
Fenzi
G F
GF
Mammoli
C
C
Battiato
S
S
Pinchera
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D007037:Hypothyroidism / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D009230:Myxedema / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism*; D013972:Thyrotropin / Q000502:physiology*
D001323:Autoantibodies; D007074:Immunoglobulin G; D005576:Colforsin; D013972:Thyrotropin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases