TY - JOUR
T1 - Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis
AU - Sumegi, Janos
AU - Barnes, Michael G.
AU - Nestheide, Shawnagay V.
AU - Molleran-Lee, Susan
AU - Villanueva, Joyce
AU - Zhang, Kejian
AU - Risma, Kimberly A.
AU - Grom, Alexei A.
AU - Filipovich, Alexandra H.
PY - 2011/4/14
Y1 - 2011/4/14
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2010-08-300046
DO - 10.1182/blood-2010-08-300046
M3 - Article
C2 - 21325597
AN - SCOPUS:79954599747
SN - 0006-4971
VL - 117
SP - e151-e160
JO - Blood
JF - Blood
IS - 15
ER -