B-cell isotype control in atopy and asthma assessed with cDNA array technology.
B-cell isotype switching and the production of IgE is regulated by a variety of gene products through different mechanisms. A better understanding of these processes has the potential to identify markers of disease and new therapeutic targets. The aim of the study was to investigate human B-cell isotype control and IgE production in atopy and asthma with cDNA array technology. Eighteen atopic asthmatic, eight atopic nonasthmatic, and fourteen healthy control subjects were included. Peripheral blood mononuclear cells were separated by gradient centrifugation, mRNA was purified, and the reverse-transcribed probes were hybridized to cDNA membranes. Group differences were assessed with the Mann-Whitney U-test. Twenty-three of seventy-eight tested IgE-related genes had significantly altered expression in atopy and asthma compared with that in the healthy subjects. The differentially expressed genes include surface molecules involved in T- and B-cell interaction and activation, cytokines, intracellular signaling products, and transcription factors. In conclusion, both atopic nonasthmatic and atopic asthmatic individuals had activated proinflammatory pathways, a minimal requirement for B-cell isotype switching, and a clear net pro-IgE cytokine climate.
Pulmonology, University Hospital of Basel, Petersgraben 4, CH-4031 Basel, Switzerland. mbrutsche@uhbs.ch
M H
MH
Brutsche
I C
IC
Brutsche
P
P
Wood
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N
Mogulkoc
A
A
Custovic
J
J
Egan
A
A
Woodcock
D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001402:B-Lymphocytes / Q000378:metabolism*; D002469:Cell Separation; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D006967:Hypersensitivity / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D012016:Reference Values; D012720:Severity of Illness Index
D018076:DNA, Complementary; D007132:Immunoglobulin Isotypes; D015375:Receptors, Interleukin-2; D007073:Immunoglobulin E