Manzardo A M, Henkhaus R, Dhillon S, Butler M G
Department of Psychiatry & Behavioral Sciences and Pediatrics, Kansas University Medical Center, Kansas City, KS 66160, USA.
Int J Dev Neurosci. 2012 Apr;30(2):121-7. doi: 10.1016/j.ijdevneu.2011.12.003. Epub 2011 Dec 16.
The pathogenesis of autistic disorder (AD) is not clearly understood but genetic factors and the immune system have been implicated. Disturbed immunoglobulin levels and autoantibodies to neuronal elements have been reported in AD including cytokines encoded by genes involved with cell proliferation, migration and adhesion but there is a paucity of data comparing cytokine levels in children with AD and unrelated siblings without AD.
We analyzed 39 plasma cytokines in 99 well-characterized children with AD between 5 and 10 years of age and 40 age and gender matched healthy unrelated siblings without AD under the same clinical assessments, specimen processing and laboratory conditions. Multiplex sandwich immunoassays were used with the Luminex fluorescent-bead based platform. Log-transformed values of the 29 cytokines meeting laboratory criteria for inclusion were analyzed by analysis of covariance with a general linear model adjusting for diagnosis, gender, diagnosis by gender interaction effects, age and days of specimen handling. The Tukey-Kramer post hoc test was used to control for multiple comparisons.
Eight of 29 cytokine levels analyzed were significantly lower in children with AD compared with unrelated siblings without the diagnosis of AD. Three of the cytokines are known to be involved with hematopoiesis and five with attraction of T-cells, natural killer cells and monocytes.
Plasma cytokine levels representing chemokines involved in the T-helper cell immune system and hematopoiesis were lower in the children with AD compared with unrelated siblings without AD necessitating further studies to confirm immunological disturbances influencing hematopiesis and antibody production in the children with AD. Linking genes that encode immune related proteins and cytokines are important to study for their impact on critical periods of brain development and function.
自闭症谱系障碍(AD)的发病机制尚不清楚,但遗传因素和免疫系统与之相关。据报道,AD患者存在免疫球蛋白水平紊乱以及针对神经元成分的自身抗体,包括与细胞增殖、迁移和黏附相关基因编码的细胞因子,但关于AD患儿与无AD的非亲属同胞的细胞因子水平比较的数据较少。
我们在相同的临床评估、样本处理和实验室条件下,分析了99名5至10岁特征明确的AD患儿和40名年龄及性别匹配的无AD的健康非亲属同胞的39种血浆细胞因子。采用基于Luminex荧光微球平台的多重夹心免疫分析法。对符合实验室纳入标准的29种细胞因子的对数转换值进行协方差分析,采用一般线性模型,对诊断、性别、诊断与性别的交互作用、年龄和样本处理天数进行校正。采用Tukey-Kramer事后检验控制多重比较。
与未诊断为AD 的非亲属同胞相比,AD患儿中29种分析的细胞因子水平中有8种显著降低。其中3种细胞因子已知与造血有关,5种与T细胞、自然杀伤细胞和单核细胞的吸引有关。
与无AD的非亲属同胞相比,AD患儿中代表参与辅助性T细胞免疫系统和造血的趋化因子的血浆细胞因子水平较低,需要进一步研究以证实影响AD患儿造血和抗体产生的免疫紊乱。研究编码免疫相关蛋白和细胞因子的基因对大脑发育和功能关键期的影响具有重要意义。