Detection of low titre TBII in patients with Graves' disease using recombinant human TSH receptor.
OBJECTIVE
We evaluated thyrotropin-binding inhibitor immunoglobulin (TBII) in sera from patients with Graves' disease (GD) by using the new human recombinant TSH receptor (TSH-R) assay to determine if it is useful for the diagnosis and follow-up of GD.


METHODS
Serum samples from 25 patients with untreated GD, 24 with relapsing GD, 15 with GD in remission and 197 treated GD patients were examined. TBII was also measured in sera from healthy individuals (n = 69).


METHODS
TBII was retrospectively measured by using the conventional porcine TBII assay (pTBII) and the human recombinant TBII assay (hTBII). Specificity was adjusted at 97.5% for both assays by receiver-operating characteristic (ROC) plot analysis, resulting in cut-offs at 10.5% inhibition (hTBII) and 9.9% (pTBII). Sensitivity was 87% for hTBII compared to 52% for pTBII (P < 0.0001).


RESULTS
Even in pTBII-positive patients, hTBII values (57.6 +/- 26.1%) were significantly (P < 0.0001) higher than pTBII values (34.2 +/- 27.6%). When 139 pTBII-negative serum samples from patients with treated GD were examined, 97 samples (69.8%) were positive for hTBII. hTBII values (23.9 +/- 17.0%) were significantly (P < 0.0001) higher than pTBII values (4.1 +/- 3.3%). hTBII was positive in 13 of 13 patients who were taking antithyroid drugs but had normal serum TSH levels. When 19 serum samples from pTBII-negative untreated patients with GD were examined, 15 out of 19 (79%) were positive for hTBII. We also examined 24 patients with relapsing GD. hTBII was positive in 16 (64%) patients, whereas seven (16%) were positive for pTBII (P < 0.01). Positivity of hTBII in these untreated or relapsing GD patients was significantly higher than that of thyroid stimulating antibodies. We then examined TBII levels in 15 patients with GD in remission who had normal serum TSH values. hTBII was positive in seven patients at the time of blood withdrawal, and GD subsequently relapsed in three hTBII-positive patients in 6 months.


CONCLUSIONS
Low TBII titres can now be followed more accurately during the course of treatment, which will also allow better longitudinal studies on the importance of TBII for the diagnosis as well as the prognosis of GD with respect to remission or relapse.
Morgenthaler
Nils G
NG
Research Laboratories, BRAHMS AG, Biotechnology Center, Berlin, Germany.
Nagata
Atsuo
A
Katayama
Shigehiro
S
Bergmann
Andreas
A
Iitaka
Makoto
M
D000818:Animals; D000911:Antibodies, Monoclonal; D013956:Antithyroid Agents / Q000627:therapeutic use; D019540:Area Under Curve; D001323:Autoantibodies / Q000032:analysis*; D016022:Case-Control Studies; D006111:Graves Disease / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating; D011237:Predictive Value of Tests; D011379:Prognosis; D011869:Radioligand Assay; D011989:Receptors, Thyrotropin / Q000032:analysis* / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012008:Recurrence; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013552:Swine; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
D000911:Antibodies, Monoclonal; D013956:Antithyroid Agents; D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; D011989:Receptors, Thyrotropin; D011994:Recombinant Proteins; C094372:thyrotropin-binding inhibitory immunoglobulin; D013972:Thyrotropin; D013974:Thyroxine