Department of Experimental Medicine, Second University of Naples , Naples , Italy ; Centre for Autism - La Forza del Silenzio , Caserta , Italy ; Cancellautismo , Florence , Italy.
Front Immunol. 2013 Jun 10;4:140. doi: 10.3389/fimmu.2013.00140. eCollection 2013.
Autism and autism spectrum disorders (ASDs) are heterogeneous, severe neuro-developmental disorders with core symptoms of dysfunctions in social interactions and communication skills, restricted interests, repetitive - stereotypic verbal and non-verbal behaviors. Biomolecular evidence points to complex gene-environmental interactions in ASDs. Several biochemical processes are associated with ASDs: oxidative stress (including endoplasmic reticulum stress), decreased methylation capacity, limited production of glutathione; mitochondrial dysfunction, intestinal dysbiosis, increased toxic metal burden, and various immune abnormalities. The known immunological disorders include: T-lymphocyte populations and function, gene expression changes in monocytes, several autoimmune-related findings, high levels of N-acetylgalactosaminidase (which precludes macrophage activation), and primary immune deficiencies. These immunological observations may result in minicolumn structural changes in the brain, as well as, abnormal immune mediation of synaptic functions. Equally, these immune dysregulations serve as the rationale for immune-directed interventions such as hematopoietic stem cells (HSCs), which are pivotal in controlling chronic inflammation and in the restoration of immunological balance. These properties make them intriguing potential agents for ASD treatments. This prospective review will focus on the current state-of-the-art knowledge and challenges intrinsic in the application of HSCs for ASD-related immunological disorders.
自闭症和自闭症谱系障碍（ASD）是一种异质性的、严重的神经发育障碍，其核心症状包括社交互动和沟通技能障碍、兴趣受限、重复刻板的言语和非言语行为。生物分子证据表明 ASD 与复杂的基因-环境相互作用有关。几种生化过程与 ASD 相关：氧化应激（包括内质网应激）、甲基化能力下降、谷胱甘肽生成有限；线粒体功能障碍、肠道菌群失调、毒性金属负荷增加以及各种免疫异常。已知的免疫性疾病包括：T 淋巴细胞群体和功能、单核细胞中的基因表达变化、几种自身免疫相关的发现、N-乙酰半乳糖胺酶水平升高（可阻止巨噬细胞激活）以及原发性免疫缺陷。这些免疫学观察结果可能导致大脑中小柱结构的改变，以及突触功能的异常免疫调节。同样，这些免疫失调为免疫导向干预提供了依据，例如造血干细胞（HSCs），它们在控制慢性炎症和恢复免疫平衡方面起着关键作用。这些特性使它们成为治疗 ASD 的潜在有吸引力的药物。本前瞻性综述将重点关注目前关于 HSCs 治疗与 ASD 相关免疫性疾病的最新知识和内在挑战。
