PMID- 26556803
OWN - NLM
STAT- MEDLINE
DCOM- 20160616
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 11
DP  - 2015
TI  - Gene Expression Profiles from Disease Discordant Twins Suggest Shared Antiviral 
      Pathways and Viral Exposures among Multiple Systemic Autoimmune Diseases.
PG  - e0142486
LID - 10.1371/journal.pone.0142486 [doi]
LID - e0142486
AB  - 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.
FAU - Gan, Lu
AU  - Gan L
AD  - Environmental Autoimmunity Group, Clinical Research Branch, National Institute of 
      Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland, 
      United States of America.
FAU - O'Hanlon, Terrance P
AU  - O'Hanlon TP
AD  - Environmental Autoimmunity Group, Clinical Research Branch, National Institute of 
      Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland, 
      United States of America.
FAU - Lai, Zhennan
AU  - Lai Z
AD  - Molecular Physiology and Therapeutics Branch, National Institute of Dental and 
      Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United 
      States of America.
FAU - Fannin, Rick
AU  - Fannin R
AD  - 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.
FAU - Weller, Melodie L
AU  - Weller ML
AD  - Molecular Physiology and Therapeutics Branch, National Institute of Dental and 
      Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United 
      States of America.
FAU - Rider, Lisa G
AU  - Rider LG
AD  - Environmental Autoimmunity Group, Clinical Research Branch, National Institute of 
      Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland, 
      United States of America.
FAU - Chiorini, John A
AU  - Chiorini JA
AD  - Molecular Physiology and Therapeutics Branch, National Institute of Dental and 
      Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United 
      States of America.
FAU - Miller, Frederick W
AU  - Miller FW
AD  - Environmental Autoimmunity Group, Clinical Research Branch, National Institute of 
      Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland, 
      United States of America.
LA  - eng
SI  - GEO/GSE74027
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Twin Study
DEP - 20151110
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Adolescent
MH  - Autoimmune Diseases/*genetics/virology
MH  - Autoimmunity/genetics
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Gene Expression Profiling
MH  - *Genes, Viral
MH  - *Herpesvirus 2, Human
MH  - Humans
MH  - Male
MH  - Transcriptome
MH  - Twins/*genetics
MH  - Young Adult
PMC - PMC4640563
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/11/12 06:00
MHDA- 2016/06/17 06:00
PMCR- 2015/11/10
CRDT- 2015/11/12 06:00
PHST- 2015/07/14 00:00 [received]
PHST- 2015/10/22 00:00 [accepted]
PHST- 2015/11/12 06:00 [entrez]
PHST- 2015/11/12 06:00 [pubmed]
PHST- 2016/06/17 06:00 [medline]
PHST- 2015/11/10 00:00 [pmc-release]
AID - PONE-D-15-30945 [pii]
AID - 10.1371/journal.pone.0142486 [doi]
PST - epublish
SO  - PLoS One. 2015 Nov 10;10(11):e0142486. doi: 10.1371/journal.pone.0142486. 
      eCollection 2015.