Cihakova D, Trebusak K, Heino M, Fadeyev V, Tiulpakov A, Battelino T, Tar A, Halász Z, Blümel P, Tawfik S, Krohn K, Lebl J, Peterson P
Institute of Medical Technology, University of Tampere, Department of Pathology, Tampere University Hospital, Tampere, Finland.
Hum Mutat. 2001 Sep;18(3):225-32. doi: 10.1002/humu.1178.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder that results in several autoimmune diseases due to the mutations in the AIRE (autoimmune regulator) gene. APECED patients develop several autoimmune endocrine disorders and are characterized by the high titer autoantibodies to organ-specific antigens such as the steroidogenic P450 cytochromes. So far, 38 mutations have been identified in the AIRE gene. We report here the genetic and autoantibody analysis of 27 APECED patients of Eastern and Central European origins and one Egyptian patient. From 54 analyzed APECED chromosomes, eight mutations were detected, four of which (T16M, W78R, IVS1_IVS4, 30-53dup23bp) are novel. The most prevalent reason for APECED in these populations was the occurrence of R257X (36 chromosomes) that has been described earlier as a common and recurrent mutation in several other populations. The analysis of humoral immunity to steroidogenic P450 cytochromes by the immunoblotting of E. coli expressed antigens in the 18 APECED patients showed that 67%, 44%, and 61% of the Eastern and Central European APECED patients had autoantibodies to P450c17, P450c21, and P450scc, respectively.
自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良（APECED）是一种罕见的隐性疾病，由于自身免疫调节因子（AIRE）基因突变导致多种自身免疫性疾病。APECED患者会出现多种自身免疫性内分泌疾病，其特征是针对器官特异性抗原（如类固醇生成的细胞色素P450）的高滴度自身抗体。到目前为止，已在AIRE基因中鉴定出38种突变。我们在此报告对27名东欧和中欧血统的APECED患者以及1名埃及患者的基因和自身抗体分析。在54条分析的APECED染色体中，检测到8种突变，其中4种（T16M、W78R、IVS1_IVS4、30-53dup23bp）是新发现的。这些人群中APECED最常见的原因是R257X的出现（36条染色体），该突变在其他一些人群中已被描述为常见的复发性突变。通过对18名APECED患者中大肠杆菌表达抗原的免疫印迹分析对类固醇生成细胞色素P450的体液免疫，结果显示，东欧和中欧APECED患者中分别有67%、44%和61%的患者对P450c17、P450c21和P450scc有自身抗体。
