The genetic and environmental basis of atopic diseases

Figures & data

Figure 1.  The three main pathways of antigen presentation and the effector mechanisms induced during the allergic reaction.

Table I.  Major candidate susceptibility genes for allergic diseases discovered to date.

Chromosome	Genes	Proposed function
20p13	ADAM33	Airway remodeling/bronchial smooth muscle contraction.
16p12	IL-4RA	Forming part of the IL-4 and IL-13 receptors.
14q11	TCR α/δ	Restricts the ability of T lymphocytes to react to specific allergens.
13q14	PHF11	Regulation of lymphocyte activation and immunoglobulin synthesis.
11q13-21	FcεRI-β	Amplifies FcεRI receptor's response to activation and stabilizes the expression of the receptor on the surface of mast cells.
7p15	NSR1	Encodes for the NSR1-B receptor found in bronchial epithelial and smooth muscle cells.
6p21-24	MHC	Restricts IgE response to certain allergens.
	TNF	Mediator of inflammatory response.
	LTα	Regulates TNF gene expression.
5q23-35	Cytokine cluster	Regulates the production of IL-4, IL-13, GM-CSF and IL-9.
	TIM family	Regulates IL-4, IL-13 production/degree of airway hypersensitivity.
	p40	Encodes for one of the two subunits of IL-12.
	ADRB2	Regulates airway's smooth muscle responsiveness.
	CD14	High affinity ligand for bacterial LPS.
2q14	DPP10	Regulates the activity of various cytokines and chemokines.
	T-bet, GATA-3, FOXP3	Regulate differentiation into Th1, Th2, and Treg cells, respectively.

ADAM33: Alpha disintegrin and metalloproteinase 33, IL-4RA: alpha chain of the IL-4 receptor, TCR α/δ: T cell receptor α/δ, PHF11: PHD finger protein 11, FcεRI-β: β chain of the high-affinity IgE receptor, NSR1: Neuropeptide S Receptor 1, MHC: Major Histocompatibility Complex, TNF: tumor necrosis factor, LTα: lymphotoxin-alpha, GM-CSF: granulocyte-macrophage colony-stimulating factor, TIM: T cell Immunoglobulin and Mucin domain, ADRB2: β2 adrenergic receptor, DPP10: dipeptidyl peptidase-10, FOXP3: forkhead box P3.

Table II.  Epidemiologic studies in support of the ‘hygiene hypothesis’. For a more extensive catalogue of relevant epidemiologic studies see reference 175.

Low rate of atopic disorders observed in	Location	Authors
Children with parasitic infections	Venezuela	Lynch et al., 1993 (137)
	Ethiopia	Yemaneberhan et al., 1997 (139)
	Ecuador	Cooper et al., 2003 (138)
Children with older siblings or attending day care	Germany	von Mutius et al., 1994 (112)
	USA	Ball et al., 2000 (114)
	USA	Celedon et al., 2003 (115)
	Brazil	Cardoso et al., 2004 (113)
Children that have grown in a farm	Canada	Ernst et al., 2000 (118)
	Denmark	Portengen et al., 2002 (119)
	USA	Elliott et al., 2004 (117)
	Norway	Eduard et al., 2004 (116)
	PARSIFAL	Alfven et al., 2006 (156)
Patients with previous tuberculosis (positive tuberculin response)	Japan	Shirakawa et al., 1997 (102)
Patients with previous hepatitis A virus infection	Italy	Matricardi et al., 1997 (104)
	USA	Matricardi et al., 2002 (105)
	Denmark	Linneberg et al., 2003 (103)
Patients with previous measles infection	Guinea Bissau	Shaheen et al., 1996 (109)

Figure 2.  Schematic representation of the immune-regulation network theory. This network is believed to be responsible for preventing the development of both autoimmune and atopic diseases.

Bloomfield SF, Stanwell-Smith R, Crevel RW, Pickup J. Too clean, or not too clean: the hygiene hypothesis and home hygiene. Clin Exp Allergy. 2006; 36: 402–25

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