The Detection of Serum IgMs to Thyroglobulin in Subacute Thyroiditis Suggests a Protective Role of IgMs in Thyroid Autoimmunity

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 6; pp. e2261 - e2270
• Main Authors: Ricci, Debora, Brancatella, Alessandro, Marinò, Michele, Rotondi, Mario, Chiovato, Luca, Vitti, Paolo, Latrofa, Francesco
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.06.2020
• Subjects: Adult; Autoantibodies - blood; Autoantibodies - immunology; Autoimmunity; Autoimmunity - immunology; Biomarkers - blood; Bovine serum albumin; Case-Control Studies; Complications; Enzyme-linked immunosorbent assay; Female; Follow-Up Studies; Glucagon; Graves Disease - blood; Graves Disease - epidemiology; Graves Disease - immunology; Graves' disease; Hashimoto Disease - blood; Hashimoto Disease - epidemiology; Hashimoto Disease - immunology; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulin M - blood; Immunoglobulin M - immunology; Italy - epidemiology; Male; Middle Aged; Prognosis; Thyroglobulin; Thyroglobulin - immunology; Thyroid diseases; Thyroid gland; Thyroiditis; Thyroiditis, Subacute - blood; Thyroiditis, Subacute - epidemiology; Thyroiditis, Subacute - immunology; Young Adult; Italy; subacute thyroiditis; Hashimoto’s thyroiditis; thyroglobulin autoantibodies; thyroglobulin; Graves’ disease; IgM
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgaa038

The role of serum immunoglobulin (Ig)Ms in autoimmune thyroid diseases is uncertain. We looked for IgMs to thyroglobulin (Tg) in patients with subacute thyroiditis (SAT), which is characterized by high serum Tg levels, the possible de novo appearance of IgGs to Tg (TgAb-IgGs), and no autoimmune sequelae. TgAb-IgMs and TgAb-IgGs were detected by binding to Tg using the enzyme-linked immunosorbent assay (ELISA). The upper reference limit of TgAb-IgMs and TgAb-IgGs was established in 40 normal subjects. We looked for TgAb-IgMs in 16 patients with SAT, 11 with Hashimoto's thyroiditis (HT), and 8 with Graves' disease (GD) who were all positive for TgAb-IgGs. IgM binding to bovine serum albumin (BSA), keyhole limpet hemocyanin (KLH), and glucagon in ELISA was measured. Inhibition of TgAb-IgMs binding to coated Tg was evaluated by preincubating serum samples or IgG-depleted samples with soluble Tg. TgAb-IgMs were positive in 10/16 patients with SAT, 2/11 with HT, and 1/8 with GD. TgAb-IgMs were higher in SAT (0.95; 0.42-1.13) (median; 25th-75th percentiles) than in HT (0.47; 0.45-0.51) and GD patients (0.35; 0.33-0.40) (P < .005 for both). IgM binding of SAT sera to BSA, KLH, and glucagon was significantly lower than Tg. Preincubation with soluble Tg reduced the binding of IgMs to coated Tg by 18.2% for serum samples and by 35.0% and 42.1% for 2 IgG-depleted samples. TgAb-IgM levels were inversely, although nonsignificantly, correlated with Tg concentrations. Tg leak associated with thyroid injury induces the production of specific TgAb-IgMs, which, in turn, increases the clearance of Tg and might prevent the establishment of a persistent thyroid autoimmune response.