PMID- 23985570
OWN - NLM
STAT- MEDLINE
DCOM- 20140716
LR  - 20131205
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Linking)
VI  - 14
IP  - 8
DP  - 2013 Dec
TI  - Genome-wide expression analysis suggests unique disease-promoting and 
      disease-preventing signatures in Pemphigus vulgaris.
PG  - 487-99
LID - 10.1038/gene.2013.44 [doi]
AB  - To evaluate pathogenetic mechanisms underlying disease development and 
      progression in the autoimmune skin disease Pemphigus vulgaris (PV), we examined 
      global peripheral blood gene expression in patients and healthy controls. Our 
      goals were to: (1) assign blood gene expression signatures to patients and 
      controls; (2) identify differentially expressed genes (DEGs) and investigate 
      functional pathways associated with these signatures; and (3) evaluate the 
      distribution of DEGs across the genome to identify transcriptional 'hot spots'. 
      Unbiased hierarchical clustering clearly separated patients from human leukocyte 
      antigen (HLA)-matched controls (MCRs; 'disease' signature), and active from 
      remittent patients ('activity' signature). DEGs associated with these signatures 
      are involved in immune response, cytoskeletal reorganization, mitogen-activated 
      protein kinase (MAPK) signaling, oxidation-reduction and apoptosis. We further 
      found that MCRs carrying the PV-associated HLA risk alleles cluster distinctly 
      from unmatched controls (UMCR) revealing an HLA-associated 'control' signature. A 
      subset of DEGs within the 'control' signature overlap with the 'disease' 
      signature, but are inversely regulated in MCR when compared with either PV 
      patients or UMCR, suggesting the existence of a 'protection' signature in healthy 
      individuals carrying the PV HLA genetic risk elements. Finally, we identified 19 
      transcriptional 'hot spots' across the signatures, which may guide future studies 
      aimed at pinpointing disease risk genes.
FAU - Dey-Rao, R
AU  - Dey-Rao R
AD  - Department of Dermatology, University at Buffalo, Buffalo, NY, USA.
FAU - Seiffert-Sinha, K
AU  - Seiffert-Sinha K
FAU - Sinha, A A
AU  - Sinha AA
LA  - eng
PT  - Journal Article
DEP - 20130829
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adult
MH  - Case-Control Studies
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - *Genome, Human
MH  - HLA Antigens/genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pemphigus/diagnosis/*genetics
MH  - *Transcriptome
EDAT- 2013/08/30 06:00
MHDA- 2014/07/17 06:00
CRDT- 2013/08/30 06:00
PHST- 2013/03/26 00:00 [received]
PHST- 2013/07/02 00:00 [revised]
PHST- 2013/07/19 00:00 [accepted]
PHST- 2013/08/30 06:00 [entrez]
PHST- 2013/08/30 06:00 [pubmed]
PHST- 2014/07/17 06:00 [medline]
AID - gene201344 [pii]
AID - 10.1038/gene.2013.44 [doi]
PST - ppublish
SO  - Genes Immun. 2013 Dec;14(8):487-99. doi: 10.1038/gene.2013.44. Epub 2013 Aug 29.