Microarray-Based Avidity Assay for Assessment of Thyroid Autoantibodies.

Area of Science:

• Immunology
• Endocrinology
• Biochemistry

Background:

• Autoimmune thyroid disease (AITD) is characterized by autoantibodies targeting thyroid antigens.
• The avidity of these autoantibodies, reflecting binding strength, is not fully understood in disease pathogenesis.
• Assessing autoantibody avidity may offer insights into disease progression and prediction.

Purpose of the Study:

• To evaluate the avidity of thyroid autoantibodies in patients with AITD and in individuals who are carriers of these antibodies without diagnosed AITD.
• To develop and validate a multiplex assay for measuring autoantibody avidity against key thyroid antigens.

Main Methods:

• A novel hydrogel microarray-based multiplex assay was developed.
• The assay incorporates a chaotrope destruction stage to quantify autoantibody avidity.
• The assay was validated across three independent cohorts, including healthy carriers, AITD patients, and type 1 diabetes (T1D) patients with thyroid autoantibodies.

Main Results:

• The study demonstrated heterogeneous avidity of autoantibodies targeting thyroglobulin (Tg) and thyroperoxidase (TPO).
• Median avidity index (AI) for anti-Tg antibodies was significantly higher in AITD patients (52.6%) and T1D carriers (92.7%) compared to healthy carriers (29.9%).
• Median AI for anti-TPO antibodies showed a similar trend, increasing from healthy carriers (39.9%) to AITD patients (73.4%), T1D carriers (83.2%), and AITD patients with thyroid neoplasm (98.5%).
• Longitudinal analysis revealed changes in anti-TPO avidity maturation over time in Hashimoto's thyroiditis patients.

Conclusions:

• Autoantibody avidity is a variable characteristic in individuals with and without diagnosed AITD.
• Further longitudinal studies are warranted to explore the maturation of autoantibody avidity in asymptomatic individuals.
• Autoantibody avidity shows potential as a prognostic marker for predicting the development and progression of autoimmune thyroid disease.