Takeshima Ken, Inaba Hidefumi, Furukawa Yasushi, Nishi Masahiro, Yamaoka Hiroyuki, Miyamoto Waka, Ota Takayuki, Doi Asako, Kawashima Hiromichi, Ariyasu Hiroyuki, Wakasaki Hisao, Furuta Hiroto, Nakao Taisei, Sasaki Hideyuki, Akamizu Takashi
The First Department of Medicine, Wakayama Medical University , Wakayama, Japan .
Thyroid. 2014 Apr;24(4):736-43. doi: 10.1089/thy.2013.0448. Epub 2014 Jan 24.
Immunoglobulin G4-related disease (IgG4-RD) is a new clinical entity that affects various organs with increased IgG4 positive plasmacytes and progressive fibrosis. While IgG4-RDs in association with Hashimoto's thyroiditis or Riedel's thyroiditis have been reported, the relationship between IgG4-RD and Graves' disease (GD) is yet unknown. To elucidate the relation of GD to IgG4-RD, serum IgG4 levels and their clinical implications in patients with GD were investigated.
In this prospective study, serum IgG4 levels were measured in 109 patients with GD and classified into two groups according to the comprehensive diagnostic criteria of IgG4-RD previously established: (i) GD with elevated-IgG4 levels (≥ 135 mg/dL), and (ii) GD with nonelevated IgG4 (<135 mg/dL).
Seven out of 109 patients with GD (6.4%) had elevated serum IgG4 levels [mean ± standard deviation (range): 175.0 ± 44.5 (136-266) mg/dL] and elevated ratios of IgG4/IgG [12.7 ± 4.5% (7.6%-21.2%)]. The remaining patients with GD had serum IgG4 levels and IgG4/IgG ratios of 39.6 ± 27.6 (3-132) mg/dL and 3.2 ± 2.2% (0.3%-11.5%), respectively. Ages in the elevated IgG4 group were significantly higher than those of the nonelevated IgG4 group: 54.7 ± 6.2 versus 43.4 ± 15.4 years, respectively. Ultrasound examinations revealed that the elevated IgG4 group had significantly increased hypoechogenic areas in the thyroid in comparison to the nonelevated IgG4 group (low echo scoring: 1.66 ± 0.81 vs. 0.61 ± 0.89, respectively). In the correlation analysis, TSAb (rs=0.385, n=42) titers were significantly correlated with se rum IgG4 levels, while they were not significantly different between the two groups. In the elevated IgG4 group, symptoms were controllable with a small dose of antithyroidal drug (ATD; n=4), a combination treatment with ATD and L-T4 (n=1), or L-T4 administration only one year after the first visit (n=2).
A small portion of GD patients harbored elevated serum IgG4 levels. They were older, had increased hypoechoic areas in the thyroid, and appeared to be responsive or prone to be hypothyroid after ATD treatment. Thus, the present study suggests the presence of a novel subtype of GD. Measuring serum IgG4 levels may help to distinguish this new entity and provide potential therapeutic options for GD.
免疫球蛋白G4相关疾病（IgG4-RD）是一种新的临床实体，可累及多个器官，伴有IgG4阳性浆细胞增多和进行性纤维化。虽然已有IgG4-RD与桥本甲状腺炎或Riedel甲状腺炎相关的报道，但IgG4-RD与Graves病（GD）之间的关系尚不清楚。为阐明GD与IgG4-RD的关系，我们对GD患者的血清IgG4水平及其临床意义进行了研究。
在这项前瞻性研究中，我们检测了109例GD患者的血清IgG4水平，并根据先前制定的IgG4-RD综合诊断标准将其分为两组：（i）IgG4水平升高（≥135mg/dL）的GD患者，以及（ii）IgG4水平未升高（<135mg/dL）的GD患者。
109例GD患者中有7例（6.4%）血清IgG4水平升高[平均值±标准差（范围）：175.0±44.5（136-266）mg/dL]，IgG4/IgG比值升高[12.7±4.5%（7.6%-21.2%）]。其余GD患者的血清IgG4水平和IgG4/IgG比值分别为39.6±27.6（3-132）mg/dL和3.2±2.2%（0.3%-11.5%）。IgG4水平升高组的年龄显著高于IgG4水平未升高组：分别为54.7±6.
