Cytokine and chemokine dysregulation in hyper-IgE syndrome.
Hyper-IgE syndrome is characterized by severe recurrent staphylococcal infections, eczema, bone abnormalities, and markedly elevated levels of immunoglobulin E (IgE). The genetic basis is not known and the central immunologic defect is largely undefined. Reduced neutrophil chemotaxis is often described, and variable T cell defects have been demonstrated in some patients. It has been hypothesized that hyper-IgE is associated with a Th1/Th2 imbalance. We wished to characterize cytokine and chemokine imbalances that might reflect the underlying disease process or reflect ongoing pathologic processes. Nine patients with hyper-IgE syndrome and six controls were studied. Radioimmunoassays, flow cytometry, and gene array analyses were performed to characterize cytokine and chemokine production. Hyper-IgE patients express more IL-12, while ENA-78, MCP-3, and eotaxin are markedly underexpressed. Underexpression of a set of chemokines could explain a number of features of hyper-IgE syndrome and may offer a new paradigm for the understanding of this disorder.
Chehimi
J
J
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Elder
M
M
Greene
J
J
Noroski
L
L
Stiehm
E R
ER
Winkelstein
J A
JA
Sullivan
K E
KE
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured / Q000187:drug effects; D054413:Chemokine CCL11; D054410:Chemokine CCL7; D054365:Chemokine CXCL5; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019742:Chemokines, CC; D019743:Chemokines, CXC; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D007589:Job Syndrome / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis / Q000235:genetics; D054409:Nicotinamide Phosphoribosyltransferase; D053495:Osteopontin; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D020917:Receptor, trkA / Q000096:biosynthesis / Q000235:genetics; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
C515456:CCL11 protein, human; C515450:CCL7 protein, human; C486263:CXCL5 protein, human; D054413:Chemokine CCL11; D054410:Chemokine CCL7; D054365:Chemokine CXCL5; D018925:Chemokines; D019742:Chemokines, CC; D019743:Chemokines, CXC; D016207:Cytokines; D018076:DNA, Complementary; D016209:Interleukin-8; D007378:Interleukins; D018945:Monocyte Chemoattractant Proteins; D010835:Phytohemagglutinins; D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin; D018664:Interleukin-12; D007371:Interferon-gamma; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D020917:Receptor, trkA; D013755:Tetradecanoylphorbol Acetate