The detection of serum IgM to thyroglobulin in subacute thyroiditis suggests a protective role of IgM in thyroid autoimmunity

Context The role of serum IgM in autoimmune thyroid diseases is uncertain. Objective We sought for IgM to thyroglobulin (Tg) in patients with subacute thyroiditis (SAT), which is characterized by high serum Tg levels, the possible de-novo appearance of IgG to Tg (TgAb-IgG) and no autoimmune sequelae. Main Outcome Measures TgAb-IgM and TgAb-IgG were detected by binding to Tg in ELISA. The upper reference limit of TgAb-IgM and TgAb-IgG was established in 40 normal subjects. TgAb-IgM were searched for in 16 SAT, 11 Hashimoto’s Thyroiditis (HT) and 8 Graves’ Disease (GD), all positive for TgAb-IgG. IgM binding to bovine serum albumin (BSA), keyhole limpet hemocyanin (KLH) and glucagon in ELISA was measured. Inhibition of TgAb-IgM binding to coated Tg was evaluated by pre-incubating serum samples or IgG-depleted samples with soluble Tg Results TgAb-IgM were positive in 10/16 SAT, 2/11 HT and 1/8 GD patients. TgAb-IgM were higher in SAT (0.95; 0.42-1.13) (median; 25th-75th percentiles) compared to HT (0.47; 0.45-0.51) and GD patients (0.35; 0.33-0.40) (p<0.005 for both). IgM binding of SAT sera to BSA, KLH and glucagon was significantly lower compared to Tg. Pre-incubation with soluble Tg reduced the binding of IgM to coated Tg by 18.2% for serum samples and by 35.0% and 42.1% for two IgG-depleted samples. TgAb-IgM levels were inversely, although non-significantly, correlated with Tg concentrations. Conclusions Tg leak associated with thyroid injury induces the production of specific TgAb-IgM, which in turn, increasing the clearance of Tg, might prevent the establishment of a persistent thyroid autoimmune response.