title: Gene Expression Profiles from Disease Discordant Twins Suggest Shared Antiviral Pathways and Viral Exposures among Multiple Systemic Autoimmune Diseases.
abstract: Viral agents are of interest as possible autoimmune triggers due to prior reported associations and widely studied molecular mechanisms of antiviral immune responses in autoimmunity. Here we examined new viral candidates for the initiation and/or promotion of systemic autoimmune diseases (SAID), as well as possible related signaling pathways shared in the pathogenesis of those disorders. RNA isolated from peripheral blood samples from 33 twins discordant for SAID and 33 matched, unrelated healthy controls was analyzed using a custom viral-human gene microarray. Paired comparisons were made among three study groups-probands with SAID, their unaffected twins, and matched, unrelated healthy controls-using statistical and molecular pathway analyses. Probands and unaffected twins differed significantly in the expression of 537 human genes, and 107 of those were associated with viral infections. These 537 differentially expressed human genes participate in overlapping networks of several canonical, biologic pathways relating to antiviral responses and inflammation. Moreover, certain viral genes were expressed at higher levels in probands compared to either unaffected twins or unrelated, healthy controls. Interestingly, viral gene expression levels in unaffected twins appeared intermediate between those of probands and the matched, unrelated healthy controls. Of the viruses with overexpressed viral genes, herpes simplex virus-2 (HSV-2) was the only human viral pathogen identified using four distinct oligonucleotide probes corresponding to three HSV-2 genes associated with different stages of viral infection. Although the effects from immunosuppressive therapy on viral gene expression remain unclear, this exploratory study suggests a new approach to evaluate shared viral agents and antiviral immune responses that may be involved in the development of SAID.
authors.affiliation: Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Terrance P
authors.initials: TP
authors.lastname: O'Hanlon
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Zhennan
authors.initials: Z
authors.lastname: Lai
authors.affiliation: Microarray Core, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.
authors.forename: Rick
authors.initials: R
authors.lastname: Fannin
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Melodie L
authors.initials: ML
authors.lastname: Weller
authors.affiliation: Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Rider
authors.affiliation: Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: John A
authors.initials: JA
authors.lastname: Chiorini
authors.affiliation: Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D001327:Autoimmune Diseases / Q000235:genetics* / Q000821:virology; D015551:Autoimmunity / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D005814:Genes, Viral; D018258:Herpesvirus 2, Human; D006801:Humans; D008297:Male; D059467:Transcriptome; D014427:Twins / Q000235:genetics*; D055815:Young Adult