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

Context: The role of serum immunoglobulin (Ig)Ms in autoimmune thyroid diseases isuncertain.Objective: 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.Main Outcome Measures: TgAb-IgMs and TgAb-IgGs were detected by binding to Tg using theenzyme-linked immunosorbent assay (ELISA). The upper reference limit of TgAb-IgMs and TgAbIgGs 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 forTgAb-IgGs. IgM binding to bovine serum albumin (BSA), keyhole limpet hemocyanin (KLH), andglucagon in ELISA was measured. Inhibition of TgAb-IgMs binding to coated Tg was evaluatedby preincubating serum samples or IgG-depleted samples with soluble Tg.Results: TgAb-IgMs were positive in 10/16 patients with SAT, 2/11 with HT, and 1/8 with GD. TgAbIgMs 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, andglucagon was significantly lower than Tg. Preincubation with soluble Tg reduced the binding ofIgMs 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.Conclusions: 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 persistentthyroid autoimmune response.