Functionality of thyroid-stimulating antibodies assessed by cryopreserved human thyroid cell bioassay

Area of Science:

• Endocrinology
• Immunology
• Cell Biology

Background:

• Autoimmune thyroid diseases, like Graves' disease, involve antibodies that can stimulate or inhibit thyroid function.
• Assessing only binding inhibition of thyroid-stimulating hormone (TSH) may not fully reflect biological activity.
• A reliable bioassay is needed to measure the functional impact of immunoglobulins in thyroid disorders.

Purpose of the Study:

• To develop and validate a convenient bioassay for measuring thyroid-stimulating activity of immunoglobulins from patients with autoimmune thyroid disease.
• To assess the prevalence and titer of thyroid-stimulating antibodies in patients with Graves' disease using the new assay.

Main Methods:

• Utilized normal human thyroid cells cultured in monolayers and cryopreserved in liquid nitrogen.
• Assessed thyroid stimulation by measuring intracellular cyclic adenosine monophosphate (cAMP) accumulation in response to immunoglobulin samples.
• Tested 45 immunoglobulin samples from untreated hyperthyroid Graves' patients and 13 from treated euthyroid Graves' patients.

Main Results:

• 71% of untreated hyperthyroid Graves' samples and 23% of treated euthyroid Graves' samples showed significant thyroid stimulation compared to normal immunoglobulin.
• 44% of positive samples exhibited low titers, with less than a 200% increase in basal cAMP levels.
• One high-titer sample demonstrated increased bioactivity upon serial dilution, suggesting the presence of an inhibitor.

Conclusions:

• A cryopreserved thyroid cell bioassay is a convenient and useful method for assessing thyroid-stimulating activity.
• Low titers of thyroid-stimulating antibodies are present in the peripheral circulation of a significant proportion of Graves' disease patients.
• Functional bioassays are crucial for a comprehensive understanding of autoimmune thyroid disease pathogenesis.