title: Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis.
abstract: Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, genetically heterogeneous autosomal recessive immune disorder that results when the critical regulatory pathways that mediate immune defense mechanisms and the natural termination of immune/inflammatory responses are disrupted or overwhelmed. To advance the understanding of FHL, we performed gene expression profiling of peripheral blood mononuclear cells from 11 children with untreated FHL. Total RNA was isolated and gene expression levels were determined using microarray analysis. Comparisons between patients with FHL and normal pediatric controls (n = 30) identified 915 down-regulated and 550 up-regulated genes with more than or equal to 2.5-fold difference in expression (P ≤ .05). The expression of genes associated with natural killer cell functions, innate and adaptive immune responses, proapoptotic proteins, and B- and T-cell differentiation were down-regulated in patients with FHL. Genes associated with the canonical pathways of interleukin-6 (IL-6), IL-10 IL-1, IL-8, TREM1, LXR/RXR activation, and PPAR signaling and genes encoding of antiapoptotic proteins were overexpressed in patients with FHL. This first study of genome-wide expression profiling in children with FHL demonstrates the complexity of gene expression patterns, which underlie the immunobiology of FHL.
authors.affiliation: Division of Bone Marrow Transplantation and Immunodeficiency, Cincinnati Children’s Hospital Medical Center, University of Cincinnati Faculty of Medicine, Cincinnati, OH, USA.
authors.forename: Janos
authors.initials: J
authors.lastname: Sumegi
authors.forename: Michael G
authors.initials: MG
authors.lastname: Barnes
authors.forename: Shawnagay V
authors.initials: SV
authors.lastname: Nestheide
authors.forename: Susan
authors.initials: S
authors.lastname: Molleran-Lee
authors.forename: Joyce
authors.initials: J
authors.lastname: Villanueva
authors.forename: Kejian
authors.initials: K
authors.lastname: Zhang
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Risma
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Grom
authors.forename: Alexandra H
authors.initials: AH
authors.lastname: Filipovich
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D000071518:Liver X Receptors; D051359:Lymphohistiocytosis, Hemophagocytic / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism; D054353:Perforin / Q000235:genetics / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: C508606:CXCL8 protein, human; C508609:IL10 protein, human; C508600:IL6 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D000071518:Liver X Receptors; D008562:Membrane Glycoproteins; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors; D011971:Receptors, Immunologic; D047490:Retinoid X Receptor alpha; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D054353:Perforin; D016753:Interleukin-10