Thyroid-stimulating antibody assay using a human thyrotropin receptor transfected cell line: relationship to clinical features of graves' disease.
OBJECTIVE
To evaluate a Chinese hamster ovary cell line transfected with the human thyrotropin (thyroid-stimulating hormone or TSH) receptor (CHO-TSHR) for its use in routine clinical testing and compare it with the currently used Fisher rat thyroid cell line (FRTL-5) relative to the cyclic adenosine monophosphate (cAMP) responses to thyroid-stimulating antibodies (TSAb).


METHODS
We analyzed 112 serum samples prospectively. TSAb were measured concurrently by both CHO-TSHR cells and FRTL-5 cells. In addition, thyrotropin-binding inhibitory immunoglobulin (TBII) was measured by a radioreceptor assay. Among the study subjects, 51 had active Graves' disease, 40 had other thyroid disease, and 21 had no thyroid disease.


RESULTS
Of 51 patients with Graves' disease, 38 (74%) had positive results in both cell assays, 4 (8%) had negative results in both assays, and 9 (18%) had positive responses with CHO-TSHR cells but negative results with FRTL-5 cells. No patient had negative findings with CHO-TSHR cells and positive results by FRTL-5 cells. All 61 patients in the other two groups had negative results by both assays (diagnostic specificity = 100%). The diagnostic sensitivity and accuracy of TSAb activity by the two cell lines (CHO-TSHR versus FRTL-5) were 92.2% versus 74.5% and 96.4% versus 88.4%, respectively. A significant correlation was noted between the TSAb activities in active Graves' sera by the two assays (r = 0.58; P<0.0001); however, values by the CHO-TSHR method were significantly higher (P<0.003). TSAb activities determined with both cell lines were positively correlated with the 24-hour thyroidal 131 I uptake (r = 0.62 and P<0.0005 in CHO-TSHR cells; r = 0.41 and P<0.05 in FRTL-5 cells). The difference in TSAb activity between patients with ophthalmopathy and those without ophthalmopathy was statistically significant with both FRTL-5 (P<0.01) and CHO-TSHR (P = 0.05) assays. The correlation between the severity of eye disease and TSAb activities was significant only with the FRTL-5 assay (P = 0.009) but not with the CHO-TSHR assay (P = 0.16). TSAb activity showed a significant positive correlation with serum thyroxine, triiodothyronine, and TBII by both cell assays. Neither cell line showed a significant correlation between TSAb activity and antimicrosomal antibody titer.


CONCLUSIONS
The CHO-TSHR cell line is superior to the standard FRTL-5 cell line in the cAMP bioassay for TSAb with reference to diagnostic sensitivity and accuracy, correlation with disease activity, simplicity, and cost.
Kim
M R
MR
Department of Endocrinology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195-5131, USA.
Faiman
C
C
Hoogwerf
B J
BJ
Gupta
M K
MK