進入胎兒腦部的母親抗體可能對自閉症有所影響


  April 3, 2008 — 最近的一篇研究中,相較於非自閉症兒童的母親,自閉症孩童的母親有40%出現比較強的胎兒腦蛋白抗體反應性、或者較多的區域有胎兒腦蛋白血清抗體;此外,自閉症孩童的母親出現退化者也比較容易有與一些胎兒腦蛋白有反應的血清抗體。
  
  這些發現認為,和其他可能的基因和/或環境因素一樣,母親經胎盤傳入的抗體也會影響自閉症。
  
  主要作者、約翰霍普金斯大學醫學院的Harvey S. Singer醫師向Medscape精神醫學表示,本研究僅代表自閉症免疫學關聯的初步結果。
  
  該研究登載於2月份的Journal of Neuroimmunology。
  
  Singer醫師表示,90%自閉症患者的潛在病因屬於未知,這一方面的認知有限,有間接證據認為免疫因素可能有所影響。
  
  有些自閉症小孩有不尋常的抗體值,但是大部分沒有自體免疫的臨床證據,這表示經胎盤傳遞給胎兒的抗體可能是造成自閉症的一個因素。
  
  該研究團隊的目標是探討母親血清抗體和腦部組織的反應性,假設在有自閉症和無自閉症小孩的母親之間會有所不同。
  
  本研究共包括了100名有自閉症小孩的母親 (平均年紀41 ± 6歲;範圍27 – 66歲),以及100名無自閉症小孩之年紀相仿的母親 (平均年紀43 ± 5歲;範圍27 – 66歲) 。
  
  使用西方印潰法(Western immunoblotting ),分析這200個母親之血清樣本中人類和嚙齒動物胎兒和成年人的腦組織;Singer醫師表示,用此技術,當抗體和一些特定分子量的抗原產生反應時會形成連結帶。
  
  【多種因素的複雜交互作用】
  研究者發現,相較於無自閉症小孩的母親,有自閉症小孩的母親明顯有較多和分子量36 kilodaltons (kDa)的人類胎兒腦組織蛋白反應抗體;有自閉症小孩的母親也明顯有較多的和分子量61 kDa的人類胎兒腦組織反應抗體,也傾向有較多的和分子量39 kDa的人類胎兒腦組織反應抗體。
  
  有自閉症小孩的母親中,47名顯示有發展性退化,對分子量36 kDa和 39 kDa的人類胎兒腦組織有較大的血清抗體反應力。
  
  Singer醫師警告表示,孕婦有胎兒腦組織抗體的事實不代表她會產下有自閉症的小孩;自閉症是一種複雜的狀況,可能原因包括了免疫、基因與環境等因素的複雜影響。
  
  他指出,在後續未發表的研究中,研究者發現,注射腦部抗體的老鼠後代出現類似自閉症的發展與社會行為。
  
  本研究接受自閉症研究聯盟( Alliance for Autism Research)之贊助。

Maternal Antibodies to Fetal B

By Marlene Busko
Medscape Medical News

April 3, 2008 — In a recent study, compared with mothers of nonautistic children, about 40% of mothers of children with autistic disorder had either stronger reactivity or more areas of reactivity of serum antibodies with fetal brain proteins. In addition, mothers of autistic children with developmental regression were more likely to have serum antibodies that reacted with certain fetal brain proteins.

These findings suggest that, along with other possible genetic and/or environmental factors, placental transfer of maternal antibodies might play a role in autism.

"This study represents only the initial step in proving an immunological association with autism," lead study author, Harvey S. Singer, MD, from the Johns Hopkins University School of Medicine, in Baltimore, Maryland, told Medscape Psychiatry.

The study was published in the February issue of the Journal of Neuroimmunology.

The underlying etiology for autism is unknown in about 90% of people, said Dr. Singer, adding that there is limited, circumstantial evidence that immune factors might play a role.

Some autistic children have unusual antibody levels, but most have no clinical evidence of autoimmune disease, which suggests that placental transfer of antibodies to the developing fetus might be a factor in autism.

The team aimed to investigate the reactivity of maternal serum antibodies with brain tissue, hypothesizing that this would be different for mothers of autistic vs nonautistic children.

The study enrolled 100 mothers (mean age, 41 ± 6 years; range, 27 – 66 years) of children with autistic disorder and 100 age-matched mothers (mean age, 43 ± 5 years; range, 27 – 66 years) of nonautistic children.

Serum samples from the 200 mothers were assayed against human and rodent fetal and adult brain tissue, using a Western immunoblotting assay. With this technique, bands are formed where antibodies react with antigens of certain molecular weights, said Dr. Singer.

Complex Interplay of Multiple Factors

The researchers found that compared with mothers of nonautistic children, significantly more mothers of children with autistic disorder had antibodies that reacted with human fetal brain tissue protein weighing 36 kilodaltons (kDa). The mothers of autistic children also had significantly greater amounts of antibody that reacted with human fetal brain tissue at 61 kDa and a trend to greater amounts of antibody that reacted with human fetal brain tissue at 39 kDa.

The 47 mothers of autistic children who showed developmental regression had serum antibodies that showed greater reactivity against human fetal brain tissue at 36 kDa and 39 kDa.

"The mere fact that a pregnant woman has antibodies against fetal brain tissue doesn’t mean she will have an autistic child," Dr. Singer cautioned. "Autism is a complex condition that is likely caused by the interplay of immune, genetic, and environmental factors."

In further unpublished studies, the investigators have found that the offspring of mice injected with brain antibodies exhibit developmental and social behaviors consistent with autism, he added.

The study was funded by the Alliance for Autism Research.

J Neuroimmunology 2008;162:261-267. Abstract

    
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