Perniola R, Falorni A, Clemente M G, Forini F, Accogli E, Lobreglio G
Paediatric Unit, Vito Fazzi Regional Hospital, Lecce, Italy.
Eur J Endocrinol. 2000 Oct;143(4):497-503. doi: 10.1530/eje.0.1430497.
The aim of the study was to assess the complex of autoantibodies which can be detected in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a rare autosomal recessive disease in which the extent of autoimmunity is still unknown.
Antibodies (A) to parathyroid glands, adrenal cortex (AC-A), ovary and testis (steroid cell antibodies, SC-A), pancreatic islet cells (IC-A), gastric parietal cells, and non-organ-specific antigens were investigated in 11 APECED patients living in the Salento region of southern Italy. Further measurements included antibodies to cytochrome P450 (CYP) enzymes: cholesterol side-chain cleavage enzyme (CYP11A), 21-hydroxylase (CYP21) and 17alpha-hydroxylase (CYP17); and to glutamic acid decarboxylase 65-kDa isoform (GAD65), tyrosine phosphatase-like protein IA2, thyroglobulin (TG), thyroperoxidase (TPO), thyrotropin receptor, liver CYP enzymes and intrinsic factor.
Antibodies to organs and subcellular fractions were detected by immunofluorescence. Radiobinding, immunoradiometric, and immunoblotting assays were used for the other measurements.
AC-A and SC-A were positive in all sera; among antibodies to adrenal CYP enzymes, only CYP21-A were present in all the patients with Addison's disease of short-medium duration (<15 years). Of three patients with Addison's disease of long duration (>15 years), two tested positive for antibodies to all three CYP enzymes, and the other for only CYP11A-A. In all sera CYP11A-A and/or CYP17-A were found. Two patients tested positive for both IC-A and GAD65-A, one for both IC-A and IA2-A, and one for GAD65-A; the fasting C-peptide assay showed no statistical difference between these four subjects and the others. All four hypothyroid patients were positive for TPO-A, while two of them were positive and two were negative for TG-A; two euthyroid subjects had positivity for TG-A. Liver-kidney microsomal antibodies reacting against the CYP2A6 were detected in two patients with autoimmune hepatitis. All but one sera contained anti-nuclear antibodies at a titre ranging between 1:20 and 1:80; however, only two patients had a connective tissue disease (Sjögren's syndrome).
Several autoantibodies may be detected in any APECED patient. Our data confirm that CYP21-A and TPO-A are major autoantibodies involved in APECED-associated Addison's disease and hypothyroidism respectively, while CYP11A-A and CYP17-A correlate with positivity for SC-A. Markers of islet cell autoimmunity are frequent, but prevalence and modalities of progression to overt beta-cell failure have to be clarified. Low-titre non-organ-specific autoantibodies are a feature of autoimmunity in APECED, but their role has yet to be fully explained.
本研究旨在评估自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良（APECED）患者体内可检测到的自身抗体复合物。APECED是一种罕见的常染色体隐性疾病，其自身免疫程度尚不清楚。
对居住在意大利南部萨伦托地区的11例APECED患者，检测其针对甲状旁腺、肾上腺皮质（AC-A）、卵巢和睾丸（类固醇细胞抗体，SC-A）、胰岛细胞（IC-A）、胃壁细胞以及非器官特异性抗原的抗体。进一步检测包括针对细胞色素P450（CYP）酶的抗体：胆固醇侧链裂解酶（CYP11A）、21-羟化酶（CYP21）和17α-羟化酶（CYP17）；以及谷氨酸脱羧酶65-kDa异构体（GAD65）、类酪氨酸磷酸酶IA2、甲状腺球蛋白（TG）、甲状腺过氧化物酶（TPO）、促甲状腺激素受体、肝脏CYP酶和内因子的抗体。
通过免疫荧光检测针对器官和亚细胞成分的抗体。其他检测采用放射结合、免疫放射测定和免疫印迹分析。
所有血清中AC-A和SC-A均为阳性；在肾上腺CYP酶抗体中，仅CYP21-A在所有病程较短（<15年）的艾迪生病患者中均有出现。在3例病程较长（>15年）的艾迪生病患者中，2例对所有三种CYP酶抗体检测呈阳性，另1例仅对CYP11A-A呈阳性。所有血清中均检测到CYP11A-A和/或CYP17-A。2例患者IC-A和GAD65-A均呈阳性，1例IC-A和IA2-A均呈阳性，1例GAD65-A呈阳性；空腹C肽检测显示这4例患者与其他患者之间无统计学差异。所有4例甲状腺功能减退患者TPO-A均为阳性，其中2例TG-A阳性，2例TG-A阴性；2例甲状腺功能正常者TG-A呈阳性。在2例自身免疫性肝炎患者中检测到与CYP2A6反应的肝肾微粒体抗体。除1例血清外，所有血清抗核抗体滴度在1:20至1:80之间；然而，仅有2例患者患有结缔组织病（干燥综合征）。
任何APECED患者体内均可检测到多种自身抗体。我们的数据证实，CYP21-A和TPO-A分别是与APECED相关的艾迪生病和甲状腺功能减退症的主要自身抗体，而CYP11A-A和CYP17-A与SC-A阳性相关。胰岛细胞自身免疫标志物常见，但向明显的β细胞功能衰竭进展的患病率和方式尚需阐明。低滴度非器官特异性自身抗体是APECED自身免疫的一个特征，但其作用尚未完全阐明。
