Dersch Rick, Tebartz van Elst Ludger, Hochstuhl Benedikt, Fiebich Bernd L, Stich Oliver, Robinson Tilman, Matysik Miriam, Michel Maike, Runge Kimon, Nickel Kathrin, Domschke Katharina, Endres Dominique
Clinic of Neurology and Neurophysiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
Section for Experimental Neuropsychiatry, Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
J Clin Med. 2020 Jul 27;9(8):2391. doi: 10.3390/jcm9082391.
The risk of developing depression is increased in patients with autoimmune thyroiditis. Autoimmune Hashimoto thyroiditis is diagnosed using the serum markers anti-thyroid peroxidase (TPO) and anti-thyroglobulin (TG) antibodies. In rare cases, patients with autoimmune thyroiditis can also suffer from the heterogeneous and ill-defined syndrome of Hashimoto encephalopathy. Biomarkers for Hashimoto encephalopathy or for any brain involvement of autoimmune thyroiditis are currently lacking. The aim of the present descriptive study was therefore to determine whether a subgroup of seropositive patients shows intrathecal anti-thyroid antibody synthesis in the cerebrospinal fluid (CSF).
Paired serum and CSF samples from 100 patients with unipolar depression were examined for anti-TPO and anti-TG antibodies using enzyme-linked immunosorbent assays. Antibody-specific indices (ASIs) were calculated for seropositive samples. These ASIs allow the differentiation between the brain-derived fraction of antibodies and antibodies which are passively diffused from the serum. ASIs >1.4 were assessed as positive for brain-derived antibodies. Additionally, for explorative evaluations, a stricter ASI limit of >2 was applied.
Anti-TPO antibodies were increased in the serum of 16 patients (16%); increased anti-TPO ASIs (>1.4) were detected in 11 of these patients (69%). Anti-TG antibodies in the serum were detected in three patients (3%), with two of them (67%) showing increased ASIs (>1.4). Overall, the authors found increased anti-thyroid antibodies in 17 of 100 patients (17%), with 13 out of 17 patients showing increased ASIs (76%; range 1.4-4.1). Choosing ASI levels of >2 led to positive findings in six out of 16 patients (38%) with anti-TPO antibodies in their serum but no increase in ASIs in three patients (0%) who were seropositive for anti-TG antibodies. The patients with elevated ASIs (N = 13) were younger than the ASI-negative patients (N = 87; p = 0.009); no differences were noted in the frequency of CSF, electroencephalography, and/or magnetic resonance imaging alterations.
A subgroup of seropositive patients showed intrathecal synthesis of anti-TPO and, more rarely, of anti-TG antibodies, which might be an indication of central autoimmunity in a subgroup of patients with unipolar depression. The confirmation of elevated ASIs as a biomarker for Hashimoto encephalopathy must await further studies. The relevance of the findings is limited by the study's retrospective and uncontrolled design.
自身免疫性甲状腺炎患者患抑郁症的风险增加。自身免疫性桥本甲状腺炎通过血清标志物抗甲状腺过氧化物酶（TPO）和抗甲状腺球蛋白（TG）抗体进行诊断。在罕见情况下，自身免疫性甲状腺炎患者也可能患有异质性且定义不明确的桥本脑病综合征。目前缺乏用于诊断桥本脑病或自身免疫性甲状腺炎任何脑部受累的生物标志物。因此，本描述性研究的目的是确定血清学阳性患者亚组是否在脑脊液（CSF）中表现出鞘内抗甲状腺抗体合成。
使用酶联免疫吸附测定法检测了100例单相抑郁症患者的配对血清和脑脊液样本中的抗TPO和抗TG抗体。计算血清学阳性样本的抗体特异性指数（ASI）。这些ASI有助于区分抗体的脑源性部分和从血清被动扩散的抗体。ASI>1.4被评估为脑源性抗体阳性。此外，为了进行探索性评估，采用了更严格的ASI界限>2。
16例患者（16%）血清中的抗TPO抗体升高；其中11例患者（69%）检测到抗TPO ASI升高（>1.4）。3例患者（3%）血清中检测到抗TG抗体，其中2例（67%）显示ASI升高（>1.4）。总体而言，作者在100例患者中的17例（17%）中发现抗甲状腺抗体升高，17例患者中有13例（76%；范围1.4 - 4.1）显示ASI升高。选择ASI水平>2导致16例血清中抗TPO抗体阳性的患者中有6例（38%）出现阳性结果，但3例抗TG抗体血清学阳性患者中无ASI升高（0%）。ASI升高的患者（N = 13）比ASI阴性患者（N = 87；p = 0.009）年轻；在脑脊液、脑电图和/或磁共振成像改变的频率方面未发现差异。
血清学阳性患者亚组显示鞘内抗TPO合成，抗TG抗体合成较少见，这可能表明单相抑郁症患者亚组存在中枢自身免疫。将升高的ASI确认为桥本脑病的生物标志物必须等待进一步研究。本研究的回顾性和非对照设计限制了研究结果的相关性。
