Iwata Naoko, Iwama Shintaro, Sugimura Yoshihisa, Yasuda Yoshinori, Nakashima Kohtaro, Takeuchi Seiji, Hagiwara Daisuke, Ito Yoshihiro, Suga Hidetaka, Goto Motomitsu, Banno Ryoichi, Caturegli Patrizio, Koike Teruhiko, Oshida Yoshiharu, Arima Hiroshi
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
Research Center of Health, Physical Fitness and Sports, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan.
Pituitary. 2017 Jun;20(3):301-310. doi: 10.1007/s11102-016-0780-8.
IgG4-related disease is a systemic inflammatory disease characterized by infiltration of IgG4-positive plasma cells into multiple organs, including the pituitary gland. Autoimmunity is thought to be involved in the pathogenesis of IgG4-related disease. The diagnosis of IgG4-related hypophysitis (IgG4-RH) is difficult because its clinical features, such as pituitary swelling and hypopituitarism, are similar to those of other pituitary diseases, including lymphocytic hypophysitis and sellar/suprasellar tumors. The presence and significance of anti-pituitary antibodies (APA) in IgG4-RH is unclear.
In this case-control study, we used single indirect immunofluorescence on human pituitary substrates to assess the prevalence of serum APA in 17 patients with IgG4-RH, 8 control patients with other pituitary diseases (lymphocytic infundibulo-neurohypophysitis, 3; craniopharyngioma, 2; germinoma, 3), and 9 healthy subjects. We further analyzed the endocrine cells targeted by the antibodies using double indirect immunofluorescence.
APA were found in 5 of 17 patients with IgG4-RH (29%), and in none of the pituitary controls or healthy subjects. The endocrine cells targeted by the antibodies in the 5 IgG4-RH cases were exclusively corticotrophs. Antibodies were of the IgG1 subclass, rather than IgG4, in all 5 cases, suggesting that IgG4 is not directly involved in the pathogenesis. Finally, antibodies recognized pro-opiomelanocortin in 2 of the cases.
Our study suggests that autoimmunity is involved in the pathogenesis of IgG4-RH and that corticotrophs are the main antigenic target, highlighting a possible new diagnostic marker for this condition.
IgG4相关疾病是一种全身性炎症性疾病，其特征是IgG4阳性浆细胞浸润包括垂体在内的多个器官。自身免疫被认为参与了IgG4相关疾病的发病机制。IgG4相关垂体炎（IgG4-RH）的诊断较为困难，因为其临床特征，如垂体肿大和垂体功能减退，与其他垂体疾病，包括淋巴细胞性垂体炎和鞍区/鞍上肿瘤相似。IgG4-RH中抗垂体抗体（APA）的存在及其意义尚不清楚。
在这项病例对照研究中，我们用人垂体底物进行单间接免疫荧光检测，以评估17例IgG4-RH患者、8例其他垂体疾病对照患者（淋巴细胞性漏斗神经垂体炎3例；颅咽管瘤2例；生殖细胞瘤3例）和9名健康受试者血清中APA的患病率。我们进一步使用双间接免疫荧光分析抗体靶向的内分泌细胞。
17例IgG4-RH患者中有5例（29%）检测到APA，垂体疾病对照患者和健康受试者均未检测到。5例IgG4-RH病例中抗体靶向的内分泌细胞均为促肾上腺皮质激素细胞。所有5例病例中抗体均为IgG1亚类，而非IgG4，这表明IgG4不直接参与发病机制。最后，2例病例中的抗体识别促肾上腺皮质激素原。
我们的研究表明自身免疫参与了IgG4-RH的发病机制，促肾上腺皮质激素细胞是主要的抗原靶点，这突出了该疾病可能的新诊断标志物。
