Gene expression profiling of the effects of intravenous immunoglobulin in human whole blood.
Intravenous immunoglobulin (IVIG) is involved in many complex mechanisms that act in synergy including expression and function of Fc receptors, complement activation, the cytokine network, interaction with the anti-idiotypic network and modulation of B and T cell activation. To gain insight into the early effects of IVIG on this broad range of activities at the gene level we performed DNA microarray analysis. Human whole blood was incubated in vitro for 4 h followed by extraction of RNA which was hybridized to a chip containing 8793 genes. About 75 upregulated genes and 21 downregulated genes were identified using a cut off for the false discovery rate of 5%. These genes are associated with a wide range of cellular immune functions in line with the broad mechanism of action of IVIG. A striking upregulation of a series of genes coding for chemokines was measured. This finding was confirmed at the protein level as pharmacologically relevant concentrations of CXCL9 and CXCL10 were measured in serum. Interestingly, IVIG shows a partial overlap of its gene expression program with lipopolysaccharide. Our data suggests multiple hypotheses regarding the pharmacology of IVIG that must be validated by complementary studies.
Ghielmetti
Marco
M
ZLB Behring AG, Wankdorfstrasse 10, 3000 Bern 22, Switzerland. marco.ghielmetti@dkf6.unibe.ch
Bellis
Michel
M
Spycher
Martin O
MO
Miescher
Sylvia
S
Vergères
Guy
G
D001769:Blood / Q000187:drug effects* / Q000276:immunology; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000097:blood / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D005796:Genes / Q000187:drug effects; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology
C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D016756:Immunoglobulins, Intravenous; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides