CD14 promoter polymorphisms in atopic families: implications for modulated allergen-specific immunoglobulin E and G1 responses.
BACKGROUND
CD14 promoter DNA sequence polymorphisms for the endotoxin receptor gene have been implicated in modulating allergen-specific immunoglobulin (Ig)E responses in randomly selected individuals with atopy. We sought to determine if a single nucleotide polymorphism in the CD14 promoter region is associated with atopy in atopic families, and to assess its influence on serum levels of CD14 and allergen-specific IgE and IgG1 responses.


METHODS
We screened 367 members of 91 Caucasian nuclear families with a history of asthma for pulmonary function by spirometry, including methacholine challenge to detect bronchial hyperreactivity, and atopy by serum total IgE and skin prick test to 14 allergens. The CD14 promoter single nucleotide polymorphism was analyzed in DNA isolated from peripheral blood mononuclear cells to identify C/C, C/T and T/T genotypes. Serum tests were done for soluble CD14 (sCD14) and dust mite-specific antibody (Der p 1-IgG1).


RESULTS
Serum sCD14 levels were not associated with clinical phenotypes (asthma, bronchial hyperreactivity or atopy). However, sCD14 levels were inversely related to both allergen-specific IgE and Der p 1-IgG1 production, but only among those with evidence of atopic sensitization. Linear regression analysis, accounting for random family effects, demonstrated a higher production of allergen-specific IgE or Der p 1-IgG1 associated with the T/T genotype and a lower level of specific IgE and IgG1 production associated with sCD14 levels.


CONCLUSIONS
An element of the innate immune system (CD14) has profound effects upon modulating the acquired allergen-specific immunoglobulin responses among those with an inherited atopic predisposition.
Jackola
Duaine R
DR
The Asthma and Allergy Program, Division of Pulmonary, Allergy and Critical Care Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA. jacko001@umn.edu
Basu
Saonli
S
Liebeler
Carol L
CL
Willaert
Rebecca
R
Luah
San-San
SS
Oetting
William
W
King
Richard A
RA
Blumenthal
Malcolm N
MN
D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology*; D039741:Antigens, Dermatophagoides / Q000097:blood / Q000276:immunology; D060829:Arthropod Proteins; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D002648:Child; D003546:Cysteine Endopeptidases; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012882:Skin Tests
D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D007074:Immunoglobulin G; D018950:Lipopolysaccharide Receptors; D007073:Immunoglobulin E; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1