Endocrinology Unit I, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Italy.
Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri, University of Pavia, Italy.
J Clin Endocrinol Metab. 2020 Jun 1;105(6). 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.
血清免疫球蛋白（Ig）M 在自身免疫性甲状腺疾病中的作用尚不确定。
我们在亚急性甲状腺炎（SAT）患者中寻找针对甲状腺球蛋白（Tg）的 IgM（TgAb-IgMs），SAT 的特点是血清 Tg 水平高，可能新出现针对 Tg 的 IgG（TgAb-IgGs），且无自身免疫后遗症。
采用酶联免疫吸附试验（ELISA）检测 TgAb-IgMs 和 TgAb-IgGs。在 40 例正常对照中建立了 TgAb-IgMs 和 TgAb-IgGs 的上限参考值。我们检测了 16 例 SAT、11 例桥本甲状腺炎（HT）和 8 例格雷夫斯病（GD）患者的 TgAb-IgMs，这些患者的 TgAb-IgGs 均为阳性。在 ELISA 中测量了 IgM 与牛血清白蛋白（BSA）、贻贝血红蛋白（KLH）和胰高血糖素的结合。通过用可溶性 Tg 预先孵育血清样本或 IgG 耗尽样本来评估 TgAb-IgMs 与包被 Tg 的结合抑制作用。
16 例 SAT 患者中有 10 例、11 例 HT 患者中有 2 例和 8 例 GD 患者中有 1 例 TgAb-IgMs 阳性。SAT 患者的 TgAb-IgMs 水平更高[0.95；0.42-1.13]（中位数；25 分位数-75 分位数），高于 HT 患者[0.47；0.45-0.51]和 GD 患者[0.35；0.33-0.40]（均 P <.005）。SAT 血清的 IgM 与 BSA、KLH 和胰高血糖素的结合明显低于 Tg。用可溶性 Tg 预孵育可使血清样本中 IgM 与包被 Tg 的结合减少 18.2%，使 2 个 IgG 耗尽样本中 IgM 与包被 Tg 的结合减少 35.0%和 42.1%。TgAb-IgM 水平与 Tg 浓度呈负相关，但无统计学意义。
与甲状腺损伤相关的 Tg 泄漏诱导了针对 Tg 的特异性 TgAb-IgMs 的产生，这反过来又增加了 Tg 的清除率，并可能阻止持续的甲状腺自身免疫反应的建立。
