Genome-level longitudinal expression of signaling pathways and gene networks in pediatric septic shock

被引:95
作者
Shanley, Thomas P.
Cvijanovich, Natalie
Lin, Richard
Allen, Geoffrey L.
Thomas, Neal J.
Doctor, Allan
Kalyanaraman, Meena
Tofil, Nancy M.
Penfil, Scott
Monaco, Marie
Odoms, Kelli
Barnes, Michael
Sakthivel, Bhuvaneswari
Aronow, Bruce J.
Wong, Hector R.
机构
[1] Cincinnati Childrens Hosp Med Ctr, Div Crit Care Med, Cincinnati, OH 45229 USA
[2] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Res Fdn, Dept Pediat, Cincinnati, OH USA
[3] Univ Michigan, CS Mott Childrens Hosp, Ann Arbor, MI 48109 USA
[4] Childrens Hosp, Oakland, CA 94609 USA
[5] Res Ctr, Oakland, CA USA
[6] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA
[7] Childrens Mercy Hosp, Kansas City, MO 64108 USA
[8] Penn State Childrens Hosp, Hershey, PA USA
[9] Washington Univ, Sch Med, St Louis, MO USA
[10] Newark Beth Israel Med Ctr, Dept Surg, Newark, NJ 07112 USA
[11] Univ Alabama Birmingham, Birmingham, AL USA
[12] DuPont Hosp Children, Delaware, OH USA
关键词
D O I
10.2119/2007-00065.Shanley
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have conducted longitudinal studies focused on the expression profiles of signaling pathways and gene networks in children with septic shock. Genome-level expression profiles were generated from whole blood-derived RNA of children with septic shock (n = 30) corresponding to day one and day three of septic shock, respectively. Based on sequential statistical and expression filters, day one and day three of septic shock were characterized by differential regulation of 2,142 and 2,504 gene probes, respectively, relative to controls (n = 15). Venn analysis demonstrated 239 unique genes in the day one dataset, 598 unique genes in the day three dataset, and 1,906 genes common to both datasets. Functional analyses demonstrated timedependent, differential regulation of genes involved in multiple signaling pathways and gene networks primarily related to immunity and inflammation. Notably, multiple and distinct gene networks involving T cell- and MHC antigen-related biology were persistently downregulated on both day one and day three. Further analyses demonstrated large scale, persistent downregulation of genes corresponding to functional annotations related to zinc homeostasis. These data represent the largest reported cohort of patients with septic shock subjected to longitudinal genome-level expression profiling. The data further advance our genome-level understanding of pediatric septic shock and support novel hypotheses.
引用
收藏
页码:495 / 508
页数:14
相关论文
共 53 条
[31]   The pediatric risk of mortality .3. Acute physiology score (PRISM III APS): A method of assessing physiologic instability for pediatric intensive care unit patients [J].
Pollack, MM ;
Patel, KM ;
Ruttimann, UE .
JOURNAL OF PEDIATRICS, 1997, 131 (04) :575-581
[32]   Epidemiology of sepals and multiple organ dysfunction syndrome in children [J].
Proulx, F ;
Fayon, M ;
Farrell, CA ;
Lacroix, J ;
Gauthier, M .
CHEST, 1996, 109 (04) :1033-1037
[33]   Expression profiling:: Toward an application in sepsis diagnostics [J].
Prucha, M ;
Ruryk, A ;
Boriss, H ;
Möller, E ;
Zazula, R ;
Herold, I ;
Claus, RA ;
Reinhart, KA ;
Deigner, P ;
Russwurm, S .
SHOCK, 2004, 22 (01) :29-33
[34]   Gene expression patterns in blood leukocytes discriminate patients with acute infections [J].
Ramilo, Octavio ;
Allman, Windy ;
Chung, Wendy ;
Mejias, Asuncion ;
Ardura, Monica ;
Glaser, Casey ;
Wittkowski, Knut M. ;
Piqueras, Bernard ;
Banchereau, Jacques ;
Palucka, A. Karolina ;
Chaussabel, Damien .
BLOOD, 2007, 109 (05) :2066-2077
[35]   Zinc homeostasis and immunity [J].
Rink, Lothar ;
Haase, Hajo .
TRENDS IN IMMUNOLOGY, 2007, 28 (01) :1-4
[36]   Agonistic monoclonal antibody against CD40 receptor decreases lymphocyte apoptosis and improves survival in sepsis [J].
Schwulst, Steven J. ;
Grayson, Mitchell H. ;
DiPasco, Peter J. ;
Davis, Christopher G. ;
Brahmbhatt, Tejal S. ;
Ferguson, Thomas A. ;
Hotchkisst, Richard S. .
JOURNAL OF IMMUNOLOGY, 2006, 177 (01) :557-565
[37]   Increased natural CD4+CD25+ regulatory T cells and their suppressor activity do not contribute to mortality in murine polymicrobial sepsis [J].
Scumpia, Philip O. ;
Delano, Matthew J. ;
Kelly, Lundra M. ;
O'Malley, Kerri A. ;
Efron, Philip A. ;
McAuliffe, Priscilla F. ;
Brusko, Todd ;
Ungaro, Ricardo ;
Barker, Tolga ;
Wynn, James L. ;
Atkinson, Mark A. ;
Reeves, Westley H. ;
Salzler, Michael J. Clare ;
Moldawer, Lyle L. .
JOURNAL OF IMMUNOLOGY, 2006, 177 (11) :7943-7949
[38]   Zinc and immune function: the biological basis of altered resistance to infection [J].
Shankar, AH ;
Prasad, AS .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 1998, 68 (02) :447S-463S
[39]  
Shanley T.P., 2006, PEDIAT CRITICAL CARE, V3rd ed., P1474, DOI [10.1016/b978-032301808-1.50099-7, DOI 10.1016/B978-032301808-1.50099-7]
[40]  
SHANLEY TP, 1995, J IMMUNOL, V154, P3454