Functional analysis of histamine release from basophils and mast cells in subjects with the Ile-181-->Leu variant of Fc epsilon RI-beta.
1. Atopy is a genetically heterogeneous disorder, but there is now strong evidence that one important locus is on chromosome 11q13. Fc epsilon RI-beta at that location has been identified as a candidate gene and variants have been associated with atopy in population studies. 2. No information is available on the functional consequences of any of these variants, and defining this may prove difficult because of the complexity of the atopy phenotype and because Fc epsilon RI beta is expressed on a range of cells with different functions, including basophils, mast cells, eosinophils and antigen-presenting Langerhan's cells. 3. We have conducted a qualitative study of mast cell and basophil histamine release in nine atopic individuals with Ile-181-->Leu mutation of Fc epsilon RI beta, and ten unrelated similarly atopic individuals without Ile-181-->Leu mutation. There were non-significant trends for Ile-181-->Leu-positive atopic subjects to produce wheal responses at lower allergen challenge in skin prick tests, and to release more histamine from basophils following in vitro allergen challenge. 4. The data do not provide decisive evidence of functional differences between atopic subjects with Ile-181-->Leu and other atopic individuals; more discriminating functional experiments are required.
Li
A
A
Osler Chest Unit, Churchill Hospital, Oxford, U.K.
Mackay
G A
GA
Hopkin
J M
JM
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage; D001491:Basophils / Q000378:metabolism*; D005260:Female; D006636:Histamine Release; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology*; D007073:Immunoglobulin E; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D011058:Pollen; D017455:Receptors, IgE / Q000235:genetics*; D012882:Skin Tests
D000888:Antibodies, Anti-Idiotypic; D017455:Receptors, IgE; D007073:Immunoglobulin E