title: Anti-inflammatory therapies of amyotrophic lateral sclerosis guided by immune pathways.
abstract: 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.
authors.affiliation: Department of Molecular, Cell and Developmental Biology, UCLA School of Medicine Los Angeles, CA 90095-1606.
authors.forename: Larry
authors.initials: L
authors.lastname: Lam
authors.affiliation: Department of Surgery, UCLA School of Medicine Los Angeles, CA 90095-7022.
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Halder
authors.affiliation: Department of Molecular, Cell and Developmental Biology, UCLA School of Medicine Los Angeles, CA 90095-1606.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Montoya
authors.affiliation: Department of Molecular, Cell and Developmental Biology, UCLA School of Medicine Los Angeles, CA 90095-1606.
authors.forename: Liudmilla
authors.initials: L
authors.lastname: Rubbi
authors.affiliation: Department of Molecular, Cell and Developmental Biology, UCLA School of Medicine Los Angeles, CA 90095-1606.
authors.forename: Arturo
authors.initials: A
authors.lastname: Rinaldi
authors.affiliation: Department of Surgery, UCLA School of Medicine Los Angeles, CA 90095-7022.
authors.forename: Bien
authors.initials: B
authors.lastname: Sagong
authors.affiliation: Department of Surgery, UCLA School of Medicine Los Angeles, CA 90095-7022.
authors.forename: Sarah
authors.initials: S
authors.lastname: Weitzman
authors.affiliation: Department of Surgery, UCLA School of Medicine Los Angeles, CA 90095-7022.
authors.forename: Rachel
authors.initials: R
authors.lastname: Rubattino
authors.affiliation: Department of Medicine, UCLA School of MedicineLos Angeles, CA 90095-1670; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLALos Angeles, CA 90095-1670.
authors.forename: Ram Raj
authors.initials: RR
authors.lastname: Singh
authors.affiliation: Department of Molecular, Cell and Developmental Biology, UCLA School of Medicine Los Angeles, CA 90095-1606.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pellegrini
authors.affiliation: Department of Surgery, UCLA School of Medicine Los Angeles, CA 90095-7022.
authors.forename: Milan
authors.initials: M
authors.lastname: Fiala
keywords: Amyotrophic lateral sclerosis; hepatic fibrosis; immune pathways; tocilizumab; vitamin E