Variability among TSH Measurements Can Be Reduced by Combining a Glycoengineered Calibrator to Epitope-Defined...

Area of Science:

• Biochemistry
• Endocrinology
• Protein Engineering

Background:

• Accurate measurement of thyroid-stimulating hormone (TSH) is challenging due to variable protein glycosylation.
• Discrepancies in TSH assay results persist despite sensitive assays, highlighting the need for standardization.
• Previous research suggests epitope expression differences between standards and samples contribute to measurement discordance.

Purpose of the Study:

• To produce glycoengineered TSH (rgTSH) with serum-type glycosylation.
• To compare the immunological behavior of rgTSH with international TSH standards.
• To evaluate rgTSH as a potential calibrator for harmonizing TSH measurements.

Main Methods:

• Recombinant glycoengineered TSH (rgTSH) was produced in engineered CHO cells for enhanced sialylation.
• Two assay groups targeting specific epitopes were developed.
• TSH levels were measured in 84 clinical samples using calibrations from the 3rd IS 81/565, 1st IRP 94/674, and rgTSH.

Main Results:

• Calibration using rgTSH significantly reduced assay percentage differences compared to the pituitary standard.
• A conversion from mIU/l (3rd IS 81/565) to ng/l (rgTSH) was established for normal and upper-normal TSH ranges.
• TSH assays targeting the main immunogenic region showed variable results, indicating a need for defined epitopes in this region.

Conclusions:

• Glycoengineered TSH with serum-type glycosylation serves as an effective new calibrator.
• This approach harmonizes TSH values, addressing assay discrepancies.
• The study demonstrates the potential of glycoengineering for improving diagnostic accuracy.