Clinica Pediatrica II, Ospedale Pediatrico Microcitemico Antonio Cao, Clinical and Molecular Medicine, University of Cagliari, Cagliari (CA), Italy.
Sardinian APECED Association, Baunei (OG), Italy.
J Clin Endocrinol Metab. 2019 Jan 1;104(1):150-162. doi: 10.1210/jc.2018-01313.
In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), autoantibodies (AutoAbs) labeling brain neurons were reported; conversely, brain MRI alterations associated with these AutoAbs were never reported.
To describe brain alterations in APECED and to correlate them with AutoAbs against glutamic acid decarboxylase (GAD), tyrosine hydroxylase (TH), and 5-tryptophan hydroxylase (5-HT) neurons.
Fourteen Sardinian patients with APECED and age-matched control subjects were recruited for MRI analysis and blood sampling to detect AutoAbs to GAD, TH, and 5-HT neurons by using rat brain sections. The majority of patients (n = 12) were investigated for AutoAbs a decade earlier, and 7 of 12 were positive for AutoAbs to GAD and TH neurons.
Patients with APECED had smaller cerebellum and gray matter volumes, with a ventricular enlargement and a total cerebrospinal fluid (CSF) increase, compared with controls (P < 0.01). In 11 of 14 patients, brain abnormalities were associated with AutoAbs to GAD or TH neurons (titer 1:100 to 15,000) that had persisted for 10 years in 7 of 11 patients. AutoAbs to 5-HT neurons were revealed in all patients with AutoAbs to TH neurons. A decrease in whole brain and cerebellum volumes (P = 0.028) was associated with AutoAbs to GAD neurons, and a CSF increase was associated with AutoAbs to GAD and TH/5-HT neurons (P < 0.05). HLA alleles did not appear to be involved in neuronal autoimmunity.
Brain alterations and neuronal AutoAbs were observed in 78.6% of Sardinian patients with APECED, suggesting a brain autoimmune reaction. Prolonged clinical follow-up must be conducted for the possible appearance of clinical neurologic consequences.
在自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良（APECED）中，报道了标记脑神经元的自身抗体（AutoAbs）；相反，从未报道过与这些 AutoAbs 相关的脑 MRI 改变。
描述 APECED 中的脑改变，并将其与针对谷氨酸脱羧酶（GAD）、酪氨酸羟化酶（TH）和 5-色氨酸羟化酶（5-HT）神经元的 AutoAbs 相关联。
14 名患有 APECED 的撒丁岛患者和年龄匹配的对照组被招募进行 MRI 分析和血液采样，以使用大鼠脑切片检测针对 GAD、TH 和 5-HT 神经元的 AutoAbs。大多数患者（n=12）在 10 年前接受了 AutoAbs 检测，其中 12 名中有 7 名对 GAD 和 TH 神经元的 AutoAbs 呈阳性。
与对照组相比，APECED 患者的小脑和灰质体积较小，脑室扩大，总脑脊液（CSF）增加（P<0.01）。在 14 名患者中的 11 名中，脑异常与针对 GAD 或 TH 神经元的 AutoAbs 相关（滴度为 1:100 至 15,000），其中 7 名患者在 11 名患者中持续存在 10 年。所有对 TH 神经元 AutoAbs 阳性的患者均显示出对 5-HT 神经元的 AutoAbs。全脑和小脑体积的减少（P=0.028）与 GAD 神经元的 AutoAbs 相关，CSF 的增加与 GAD 和 TH/5-HT 神经元的 AutoAbs 相关（P<0.05）。HLA 等位基因似乎并未参与神经元自身免疫。
在 78.6%的撒丁岛 APECED 患者中观察到脑改变和神经元 AutoAbs，提示存在脑自身免疫反应。必须进行长期的临床随访，以观察可能出现的临床神经系统后果。
