Lam Larry, Halder Ramesh C, Montoya Dennis J, Rubbi Liudmilla, Rinaldi Arturo, Sagong Bien, Weitzman Sarah, Rubattino Rachel, Singh Ram Raj, Pellegrini Matteo, Fiala Milan
Department of Molecular, Cell and Developmental Biology, UCLA School of Medicine Los Angeles, CA 90095-1606.
Department of Surgery, UCLA School of Medicine Los Angeles, CA 90095-7022.
Am J Neurodegener Dis. 2015 Dec 28;4(2):28-39. eCollection 2015.
Sporadic ALS patients display heterogeneous immune pathways in peripheral blood mononuclear cells (PBMCs). We tested nine sALS patients and one unaffected identical twin of an index case by RNA-Seq of PBMCs. The inflammatory patients (n = 3) clustered into a subset with an inflammatory Th1/Th17 signature and the non-inflammatory patients (n = 7) into another subset with a B cell signature. The inflammatory subset was remarkable for granulocyte and agranulocyte diapedesis, hepatic fibrosis, roles of cytokines and metalloproteases. The non-inflammatory subset was highlighted by degradation of vitamin E, serotonin and nucleotides, altered T cell and B cell signaling, agranulocyte diapedesis, and up regulation of B cell genes. Identification of these differentially regulated pathways in sALS patients may guide the choice of anti-inflammatory therapies.
散发性肌萎缩侧索硬化症（sALS）患者外周血单核细胞（PBMCs）中存在异质性免疫途径。我们通过PBMCs的RNA测序对9例sALS患者和1例指数病例的未受影响的同卵双胞胎进行了检测。炎症性患者（n = 3）聚集为具有炎症性Th1/Th17特征的一个亚组，非炎症性患者（n = 7）聚集为具有B细胞特征的另一个亚组。炎症亚组在粒细胞和无粒细胞渗出、肝纤维化、细胞因子和金属蛋白酶的作用方面表现突出。非炎症亚组的特点是维生素E、5-羟色胺和核苷酸降解，T细胞和B细胞信号改变，无粒细胞渗出以及B细胞基因上调。sALS患者中这些差异调节途径的鉴定可能会指导抗炎治疗的选择。
