The Key Events Dose-Response Framework: a foundation for examining variability in elicitation thresholds for food allergens.
Food allergies are caused by immunological reactions in individuals sensitized to normal protein components of foods. For any given sensitized individual, the severity of a reaction is generally assumed to be proportional to the dose of allergenic protein. There is substantial clinical evidence that "threshold" doses exist for the elicitation of an allergic reaction; however, the threshold (i.e., lowest dose that elicits a reaction) varies substantially across the sensitized population. Current approaches to protecting sensitized individuals from exposure to food allergens are highly qualitative (i.e., they rely on food avoidance). The Key Events Dose-Response Framework is an analytical approach for refining understanding of the biological basis of the dose-response. Application of this approach to food allergy provides a foundation for a more rigorous quantitative understanding of variability in allergic response. This study reviews the allergic disease process and the current approaches to identifying thresholds for food allergens. The pathway of key biological events occurring between food intake and allergic response is considered, along with factors that may determine the nature and severity of response to food allergens. Data needs, as well as implications for identifying thresholds, and for characterizing variability in thresholds, are also discussed.
Taylor
Steve L
SL
Food Allergy Research and Resource Program, Dept. of Food Science & Technology, University of Nebraska, Lincoln, NE, USA.
Gendel
Steven M
SM
Houben
Geert F
GF
Julien
Elizabeth
E
D000465:Algorithms; D000485:Allergens / Q000009:adverse effects*; D004306:Dose-Response Relationship, Immunologic; D005512:Food Hypersensitivity; D006801:Humans; D011634:Public Health
D000485:Allergens
Food Chem Toxicol. 2009 Jun;47(6):1198-204
19232533
Curr Allergy Asthma Rep. 2005 Jan;5(1):80-5
15659269
Biochem J. 2006 May 1;395(3):463-72
16372900
Med Clin North Am. 2006 Jan;90(1):97-127
16310526
Ann Allergy. 1988 Dec;61(6 Pt 2):47-52
3264668
Curr Opin Allergy Clin Immunol. 2006 Jun;6(3):207-13
16670516
Curr Opin Allergy Clin Immunol. 2004 Jun;4(3):235-40
15126948
J Allergy Clin Immunol. 2007 Nov;120(5):1172-7
17935766
J Allergy Clin Immunol. 2000 Mar;105(3):582-6
10719311
J Allergy Clin Immunol. 1989 Feb;83(2 Pt 1):435-40
2918186
Curr Opin Allergy Clin Immunol. 2004 Jun;4(3):205-9
15126943
Toxicol Appl Pharmacol. 1985 Nov;81(2):241-9
3933141
Br J Dermatol. 1997 Feb;136(2):153-8
9068723
J Allergy Clin Immunol. 2008 Jun;121(6):1331-6
18539191
Clin Exp Allergy. 2004 May;34(5):689-95
15144458
N Engl Reg Allergy Proc. 1986 Nov-Dec;7(6):504-10
3475552
J Allergy Clin Immunol. 2008 Feb;121(2):320-5
18086492
J Allergy Clin Immunol. 2003 Sep;112(3):616-23
13679824
Food Chem Toxicol. 2007 May;45(5):691-701
17343968
J Allergy Clin Immunol. 2007 Jul;120(1):171-6
17544097
Food Chem Toxicol. 2008 May;46(5):1437-43
18358932
Crit Rev Food Sci Nutr. 1996;36 Suppl:S91-118
8959380
Pediatrics. 2003 Jun;111(6 Pt 3):1595-600
12777598
Pediatrics. 2003 Jun;111(6 Pt 3):1601-8
12777599
J Allergy Clin Immunol. 2002 Jul;110(1):117-24
12110830
N Engl J Med. 2008 Jan 3;358(1):28-35
18172172
Int Arch Allergy Immunol. 2001 Apr;124(4):461-9
11340329
Nat Biotechnol. 2008 Jan;26(1):73-81
18183024
Allergy. 2002 Oct;57(10):873-5
12269931
Pediatr Allergy Immunol. 2006 Aug;17(5):356-63
16846454
Clin Exp Allergy. 1995 Jul;25 Suppl 1:7-9
8542462
J Pediatr. 1990 Jun;116(6):862-7
2348289
J Food Prot. 2008 May;71(5):1043-88
18522044
Int Arch Allergy Immunol. 2003 Sep;132(1):13-24
14555854
Mar Biotechnol (NY). 2003 Jul-Aug;5(4):339-48
14719162
Crit Rev Food Sci Nutr. 2009 Sep;49(8):682-9
19690994
Am J Physiol Gastrointest Liver Physiol. 2007 Dec;293(6):G1234-43
17916645
Allergy. 2001 Jun;56(6):478-90
11421891
Int J Dermatol. 1980 Jan-Feb;19(1):7-17
7358443
J Allergy Clin Immunol. 1995 Jun;95(6):1179-90
7797786
Crit Rev Food Sci Nutr. 1996;36 Suppl:S69-89
8959379
Allergy. 2002 Aug;57(8):741-6
12121196
Food Chem Toxicol. 2007 Jan;45(1):49-54
16979276