Singh Vijendra K, Lin Sheren X, Newell Elizabeth, Nelson Courtney
Department of Biology and Biotechnology Center, Utah State University, Logan, Utah 84322, USA.
J Biomed Sci. 2002 Jul-Aug;9(4):359-64. doi: 10.1007/BF02256592.
Autoimmunity to the central nervous system (CNS), especially to myelin basic protein (MBP), may play a causal role in autism, a neurodevelopmental disorder. Because many autistic children harbor elevated levels of measles antibodies, we conducted a serological study of measles-mumps-rubella (MMR) and MBP autoantibodies. Using serum samples of 125 autistic children and 92 control children, antibodies were assayed by ELISA or immunoblotting methods. ELISA analysis showed a significant increase in the level of MMR antibodies in autistic children. Immunoblotting analysis revealed the presence of an unusual MMR antibody in 75 of 125 (60%) autistic sera but not in control sera. This antibody specifically detected a protein of 73-75 kD of MMR. This protein band, as analyzed with monoclonal antibodies, was immunopositive for measles hemagglutinin (HA) protein but not for measles nucleoprotein and rubella or mumps viral proteins. Thus the MMR antibody in autistic sera detected measles HA protein, which is unique to the measles subunit of the vaccine. Furthermore, over 90% of MMR antibody-positive autistic sera were also positive for MBP autoantibodies, suggesting a strong association between MMR and CNS autoimmunity in autism. Stemming from this evidence, we suggest that an inappropriate antibody response to MMR, specifically the measles component thereof, might be related to pathogenesis of autism.
针对中枢神经系统(CNS)的自身免疫,尤其是针对髓鞘碱性蛋白(MBP)的自身免疫,可能在自闭症(一种神经发育障碍)中起因果作用。由于许多自闭症儿童体内麻疹抗体水平升高,我们开展了一项关于麻疹-腮腺炎-风疹(MMR)和MBP自身抗体的血清学研究。我们使用125名自闭症儿童和92名对照儿童的血清样本,通过酶联免疫吸附测定(ELISA)或免疫印迹法检测抗体。ELISA分析显示自闭症儿童体内MMR抗体水平显著升高。免疫印迹分析显示,125份自闭症血清中有75份(60%)存在一种异常的MMR抗体,而对照血清中未检测到。这种抗体特异性地检测到MMR中一种73 - 75kD的蛋白质。用单克隆抗体分析这条蛋白带时,其对麻疹血凝素(HA)蛋白呈免疫阳性,但对麻疹核蛋白以及风疹或腮腺炎病毒蛋白呈免疫阴性。因此,自闭症血清中的MMR抗体检测到的是麻疹HA蛋白,这是疫苗中麻疹亚单位所特有的。此外,超过90%的MMR抗体阳性自闭症血清对MBP自身抗体也呈阳性,这表明在自闭症中MMR与中枢神经系统自身免疫之间存在很强的关联。基于这一证据,我们认为对MMR,特别是其麻疹成分的不适当抗体反应可能与自闭症的发病机制有关。