Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis

Janos Sumegi, Michael G. Barnes, Shawnagay V. Nestheide, Susan Molleran-Lee, Joyce Villanueva, Kejian Zhang, Kimberly A. Risma, Alexei A. Grom, Alexandra H. Filipovich

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e151-e160
JournalBlood
Volume117
Issue number15
DOIs
StatePublished - Apr 14 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis'. Together they form a unique fingerprint.

  • Cite this

    Sumegi, J., Barnes, M. G., Nestheide, S. V., Molleran-Lee, S., Villanueva, J., Zhang, K., Risma, K. A., Grom, A. A., & Filipovich, A. H. (2011). Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis. Blood, 117(15), e151-e160. https://doi.org/10.1182/blood-2010-08-300046