Greer Judith M, Broadley Simon, Pender Michael P
Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia.
School of Medicine, Griffith University, Southport, QLD, Australia.
Front Immunol. 2017 May 8;8:514. doi: 10.3389/fimmu.2017.00514. eCollection 2017.
Several lines of evidence suggest a definite and unique link between CNS demyelinating diseases and autoimmune thyroid disease (AITD). The aim of the current study was to systematically compare the clinical and laboratory features of patients with coexistent AITD and CNS demyelinating disease with those of patients with just CNS demyelinating disease. Forty-four patients with coexisting CNS demyelinating disease and AITD were identified and their clinical and radiological features were recorded. Blood and DNA were collected and tested for HLA type and for the response of T cells and antibodies to a variety of antigens. Patients with multiple sclerosis (MS) without AITD and healthy individuals were included as controls. Patients with coexisting AITD and CNS demyelinating disease were almost exclusively female (43/44) and had prominent spinal cord involvement as the main neurological finding. The HLA molecules carried by individuals with CNS demyelinating disease and AITD differed from both other MS patients and healthy individuals. Furthermore, patients with both CNS disease and AITD showed less T cell reactivity than patients with MS alone to myelin proteolipid protein, but, compared to other groups, showed elevated levels of T cell reactivity to the calcitonin gene-related peptide, which is present in both the CNS and the thyroid, and elevated levels of T cell and antibody to the leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4), a molecule that is expressed in the brainstem and spinal cord, and which is a homolog of the thyroid-stimulating hormone receptor. We suggest that reactivity of autoreactive immune cells in these patients against antigens present in both the thyroid and the spinal cord is a potential mechanism underlying the pattern of lesion development in the CNS in patients with coexisting AITD and MS and might indicate a novel mechanism of disease pathogenesis in these patients.
多项证据表明中枢神经系统脱髓鞘疾病与自身免疫性甲状腺疾病（AITD）之间存在明确且独特的联系。本研究的目的是系统比较合并AITD和中枢神经系统脱髓鞘疾病患者与仅患有中枢神经系统脱髓鞘疾病患者的临床和实验室特征。确定了44例合并中枢神经系统脱髓鞘疾病和AITD的患者，并记录了他们的临床和放射学特征。采集血液和DNA，检测HLA类型以及T细胞和抗体对多种抗原的反应。将无AITD的多发性硬化症（MS）患者和健康个体作为对照。合并AITD和中枢神经系统脱髓鞘疾病的患者几乎均为女性（43/44），主要神经学表现为脊髓受累突出。患有中枢神经系统脱髓鞘疾病和AITD的个体所携带的HLA分子与其他MS患者和健康个体均不同。此外，与仅患MS的患者相比，患有中枢神经系统疾病和AITD的患者对髓磷脂蛋白脂蛋白的T细胞反应性较低，但与其他组相比，对降钙素基因相关肽的T细胞反应性水平升高，降钙素基因相关肽存在于中枢神经系统和甲状腺中，并且对富含亮氨酸重复序列的G蛋白偶联受体4（LGR4）的T细胞和抗体水平升高，LGR4是一种在脑干和脊髓中表达的分子，是促甲状腺激素受体的同源物。我们认为，这些患者中自身反应性免疫细胞对甲状腺和脊髓中均存在的抗原的反应性是合并AITD和MS的患者中枢神经系统病变发展模式的潜在机制，并且可能表明这些患者存在疾病发病的新机制。
