Ziemnicka Katarzyna, Gut Paweł, Gołąb Monika, Dworacki Grzegorz, Wrotkowska Elżbieta, Stajgis Marek, Katulska Katarzyna, Rabska-Pietrzak Barbara, Obara-Moszyńska Monika, Niedziela Marek, Budny Bartłomiej, Kałużna Małgorzata, Waśko Ryszard, Ruchała Marek
Chair and Department of Endocrinology, Metabolism and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland.
Chair of Clinical Immunology, Department of Immunology, Poznan University of Medical Sciences, Poznan, Poland.
Arch Immunol Ther Exp (Warsz). 2016 Dec;64(6):485-495. doi: 10.1007/s00005-016-0386-x. Epub 2016 Mar 12.
The role of autoimmunization in the pathogenesis of pituitary disorders is poorly understood. The presence of pituitary autoantibodies (APA) has been detected in various pituitary disorders. Their role, however, remains elusive. Childhood-onset combined pituitary hormone deficiency (CPHD) may be caused by environmental or genetic factors. In some of patients, causes of the disease remain unclear and contributions of autoimmune processes have been postulated. The aim of this study was to identify the microsomes-derived pituitary antigens (MPA) as potential immunogenic autoantigens in patients with hypopituitarism, therefore 62 CPHD patients, 100 healthy controls and five autoimmune polyglandular syndrome type II (APS II) patients were included in the study. The clinical evaluation included hormonal tests and magnetic resonance imaging of the pituitary. The sources of MPA were pituitary glands taken from autopsies. Isolated MPA were then separated on SDS-PAGE gel and incubated with sera obtained from patients and controls. Microsomal APA were detected using Western blot and radioimmunological method. In all CPHD and APS II patients and in 9 % individuals from control group marked immunoreactivity was detected against MPA. Antibodies showed high affinity to 67, 60, 50 and 36 kDa MPAs. Since the identified autoantigens were of unknown nature, an in silico exploration of UniProt database was applied and indicated their possible relationship with chaperones, golgins and already known autoantigens like GAD67. Reactivity against MPA indicates that these proteins certainly play a role in the processes undergoing within pituitary of CPHD patients. The identification and further detailed studies on their role in the pathogenesis of CPHD should be continued.
自身免疫在垂体疾病发病机制中的作用尚不清楚。在各种垂体疾病中均检测到垂体自身抗体（APA）的存在。然而，它们的作用仍然难以捉摸。儿童期起病的联合垂体激素缺乏症（CPHD）可能由环境或遗传因素引起。在一些患者中，疾病的病因仍不明确，有人推测自身免疫过程可能起了作用。本研究的目的是确定微粒体衍生的垂体抗原（MPA）作为垂体功能减退患者潜在的免疫原性自身抗原，因此本研究纳入了62例CPHD患者、100例健康对照和5例自身免疫性多内分泌腺综合征II型（APS II）患者。临床评估包括激素检测和垂体磁共振成像。MPA的来源是取自尸检的垂体。然后将分离出的MPA在SDS-PAGE凝胶上进行分离，并与患者和对照的血清孵育。使用蛋白质印迹法和放射免疫法检测微粒体APA。在所有CPHD和APS II患者以及9%的对照组个体中均检测到针对MPA的明显免疫反应性。抗体对67、60、50和36 kDa的MPA表现出高亲和力。由于所鉴定的自身抗原性质未知，因此对UniProt数据库进行了计算机探索，结果表明它们可能与伴侣蛋白、高尔基体蛋白以及已知的自身抗原如GAD67有关。对MPA的反应性表明这些蛋白质肯定在CPHD患者垂体内部发生的过程中起作用。应继续对其在CPHD发病机制中的作用进行鉴定和进一步的详细研究。
