Search for Quantitative Trait Loci of Atopy-associated Immune Responses Using Allergen-specific IgG1 As an "endophenotype"

Overview

Journal Hum Immunol

Specialty Allergy & Immunology

Date 2007 Oct 27

PMID 17961772

Citations 1

Authors

Duaine R Jackola

Michael B Miller

Carol L Liebeler

Malcolm N Blumenthal

Affiliations

Soon will be listed here.

Abstract

Inherited atopic diseases of humans arise from adverse adaptive humoral responses to noninfectious environmental allergens. We previously reported that allergen-specific IgG1 provides more reliable heritability estimates for responses to allergens than total IgE. Genome scans were done for 91 Caucasian nuclear families with history of atopy for total IgE and IgG1 produced against a common major allergen from house dust mite, Der p 1. Suggestive associations for Der p 1-IgG1 production were found at 7 quantitative trait loci (QTL) (logarithm of the odds, LOD > or = 1.23; p < or = 0.009) with QTL-specific heritabilities of 73%-80%. Scans using total IgE found suggestive associations for 12 QTLs (LOD > or = 1.44; p < or = 0.004), but QTL-specific heritabilities only in the range of 30%-35%. Allergen-specific IgG1 is a suitable "endophenotype" to be used in searches for genes associated with atopy-associated humoral immune responses to common aeroallergens.

Citing Articles

Two loci on chromosome 5 are associated with serum IgE levels in Labrador retrievers.

Owczarek-Lipska M, Lauber B, Molitor V, Meury S, Kierczak M, Tengvall K PLoS One. 2012; 7(6):e39176.

PMID: 22720065 PMC: 3376118. DOI: 10.1371/journal.pone.0039176.

References

Almasy L, Blangero J . Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet. 1998; 62(5):1198-211. PMC: 1377101. DOI: 10.1086/301844. View

Tangye S, Ferguson A, Avery D, Ma C, Hodgkin P . Isotype switching by human B cells is division-associated and regulated by cytokines. J Immunol. 2002; 169(8):4298-306. DOI: 10.4049/jimmunol.169.8.4298. View

Pierson L, Allauzen S, Blumenthal M, Rosenberg A . An automated method for determination of antibody affinity distribution functions with nanogram quantities. J Immunol Methods. 1998; 211(1-2):97-109. DOI: 10.1016/s0022-1759(97)00204-4. View

Jackola D . Random allergen-specific IgE expression in atopic families: evidence for inherited "stochastic bias" in adverse immune response development to non-infectious antigens. Mol Immunol. 2007; 44(10):2549-57. PMC: 1987375. DOI: 10.1016/j.molimm.2006.12.018. View

Hasbold J, Corcoran L, Tarlinton D, Tangye S, Hodgkin P . Evidence from the generation of immunoglobulin G-secreting cells that stochastic mechanisms regulate lymphocyte differentiation. Nat Immunol. 2003; 5(1):55-63. DOI: 10.1038/ni1016. View

Jung S, Siebenkotten G, Radbruch A . Frequency of immunoglobulin E class switching is autonomously determined and independent of prior switching to other classes. J Exp Med. 1994; 179(6):2023-6. PMC: 2191511. DOI: 10.1084/jem.179.6.2023. View

Abecasis G, Cherny S, Cookson W, Cardon L . Merlin--rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet. 2001; 30(1):97-101. DOI: 10.1038/ng786. View

Ober C, Hoffjan S . Asthma genetics 2006: the long and winding road to gene discovery. Genes Immun. 2006; 7(2):95-100. DOI: 10.1038/sj.gene.6364284. View

Marsh D . Approaches toward the genetic analysis of complex traits: asthma and atopy. Am J Respir Crit Care Med. 1997; 156(4 Pt 2):S133-8. DOI: 10.1164/ajrccm.156.4.12tac11. View

10.

Batard T, Basuyaux B, Laroze A, Lambin P, Bremard-Oury C, Aucouturier P . Isotypic analysis of grass-pollen-specific immunoglobulins in human plasma. 2. Quantification of the IgE, IgM, IgA class and the IgG subclass antibodies. Int Arch Allergy Immunol. 1993; 102(3):279-87. DOI: 10.1159/000236537. View

11.

Batard T, Basuyaux B, Lambin P, Bremard-Oury C, Hamilton R, David B . Isotypic analysis of grass pollen-specific immunoglobulins in human plasma. 1. Specialization of certain classes and subclasses in the immune response. Int Arch Allergy Immunol. 1993; 100(1):68-78. DOI: 10.1159/000236390. View

12.

Geha R, Jabara H, Brodeur S . The regulation of immunoglobulin E class-switch recombination. Nat Rev Immunol. 2003; 3(9):721-32. DOI: 10.1038/nri1181. View

13.

Jackola D, Pierson-Mullany L, Liebeler C, Blumenthal M, Rosenberg A . Variable binding affinities for allergen suggest a 'selective competition' among immunoglobulins in atopic and non-atopic humans. Mol Immunol. 2002; 39(5-6):367-77. DOI: 10.1016/s0161-5890(02)00108-6. View

14.

Jackola D, Liebeler C, Lin C, Chiu Y, Blumenthal M, Rosenberg A . Evidence that negative feedback between antibody concentration and affinity regulates humoral response consolidation to a non-infectious antigen in infants. Mol Immunol. 2004; 42(1):19-30. DOI: 10.1016/j.molimm.2004.07.006. View

15.

. Worldwide variations in the prevalence of asthma symptoms: the International Study of Asthma and Allergies in Childhood (ISAAC). Eur Respir J. 1998; 12(2):315-35. DOI: 10.1183/09031936.98.12020315. View

16.

. A genome-wide search for asthma susceptibility loci in ethnically diverse populations. Nat Genet. 1997; 15(4):389-92. DOI: 10.1038/ng0497-389. View

17.

Liebeler C, Basu S, Jackola D . Allergen-specific IgG1 provides parsimonious heritability estimates for atopy-associated immune responses to allergens. Hum Immunol. 2007; 68(2):113-21. PMC: 1868472. DOI: 10.1016/j.humimm.2006.12.001. View

18.

Jackola D, Liebeler C, Blumenthal M, Rosenberg A . Random outcomes of allergen-specific responses in atopic families. Clin Exp Allergy. 2004; 34(4):540-7. DOI: 10.1111/j.1365-2222.2004.1920.x. View

19.

Jackola D, Blumenthal M, Rosenberg A . Evidence for two independent distributions of serum immunoglobulin E in atopic families: cognate and non-cognate IgE. Hum Immunol. 2004; 65(1):20-30. DOI: 10.1016/j.humimm.2003.10.012. View