HLA‐DR and HLA‐DP genotypes and immunoglobulin E responses to common major allergens

Young, R. P.; Dekker, James; Wordsworth, B P; Schou, C.; Pile, K; Matthiesen, Finn; Rosenberg, William; Bell, J I; Hopkin, J. M.; Cookson, W. O. C. M.

doi:10.1111/j.1365-2222.1994.tb00931.x

Cited by 153 publications

(106 citation statements)

References 30 publications

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“…A strong and consistent association has been found between a ragweed antigen (Amb a V) and HLA-DR2 (HLA-DRB1*1501). 20 Other confirmed associations include Alt a I (from the mould Alternaria alternata) and DRB1*04, 21 Bet v I (from Birch tree pollen Betula verrucosa) and DRB3*0101, 22,23 Par o I (from the weed Parietaria officinalis) and DRB1*1101 and/or 1104, 24 and cockroach allergy and DRB1*0101 (in Hutterites) or DRB1*0102 (in African Americans). 25 Many other associations have been claimed, but have not been replicated (see 26 for review), perhaps as a result of small sample sizes, and failure to correct for multiple comparisons or hidden admixture.…”

Section: Discussionmentioning

confidence: 99%

Association between quantitative traits underlying asthma and the HLA-DRB1 locus in a family-based population sample

et al. 2001

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The region of human chromosome 6 containing the MHC has been identified as influencing asthma and atopy (allergy) by several genome-wide searches. The MHC contains many genes with potential effects on innate and specific immunity. As a first step in dissecting MHC influences on asthma and its underlying quantitative phenotypes, we have examined the HLA-DRB1 locus in a population sample consisting of 1004 individuals from 230 families from the rural Australian town of Busselton. The locus was strongly associated with the (log e ) total serum IgE concentration, accounting for 4.0% of the s 2 (variance) in that trait (multiallelic test, P=0.00001). The locus also influenced specific IgE titres to common allergens (multi-allelic tests, 2.8% s 2 for the house dust mite allergen Der p I, P=0.0013; 3.0% of s 2 for Der p II, P=0.0007; and 2.1% of s 2 for the cat allergen Fel d I, P=0.014). No associations were found to the categorical phenotype of asthma, or to the quantitative traits of peripheral blood eosinophil counts and bronchial hyper-responsiveness. Transmission disequilibrium tests excluded genetic admixture as a cause of false-positive findings. The results indicate that HLA-DRB1 alleles modulate the total serum IgE concentration and IgE responses to allergens, but do not account for the previous observations of linkage of asthma to the MHC. European Journal of Human Genetics (2001) 9, 341 ± 346.

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Section: Discussionmentioning

confidence: 99%

Association between quantitative traits underlying asthma and the HLA-DRB1 locus in a family-based population sample

et al. 2001

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“…In addition, HLA-DRB1*01 was also identified as the main restriction element for presentation of Art v 1 22–36 [68]. In the past, type I hypersensitivity to certain major allergens such as Fel d 1, Alt a 1 or bee venom has been associated with particular HLA class II phenotypes, but this association was less clear [69, 70] and these publications did not include analyses at the T cell epitope level. …”

Section: T Cell Recognitionmentioning

confidence: 99%

The Spectrum of Allergens in Ragweed and Mugwort Pollen

Wopfner

Gadermaier

Egger

et al. 2005

Int Arch Allergy Immunol

161

132

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Ragweed and mugwort are important allergenic weeds belonging to the Asteraceae or Compositae plant family. Pollen of mugwort is one of the main causes of allergic reactions in late summer and autumn in Europe and affects about 10–14% of the patients suffering from pollinosis. Ragweed pollen represents the major source of allergenic protein in the United States, with a prevalence of about 50% in atopic individuals. In Europe, ragweed allergy is now rapidly increasing particularly in certain areas in France, Italy, Austria, Hungary, Croatia, and Bulgaria. Amb a 1 and Art v 1, the major allergens of ragweed and mugwort, respectively, are unrelated proteins. Amb a 1 is an acidic 38-kDa nonglycosylated protein. The natural protein undergoes proteolysis during purification and is cleaved into a 26-kDa alpha chain, which associates noncovalently with the beta chain of 12 kDa. The two-chain form seems to be immunologically indistinguishable from the full-length molecule. Art v 1 is a basic glycoprotein comprising two domains: an N-terminal cysteine-rich, defensin-like domain and a C-terminal proline/hydroxyproline-rich module. The proline/hydroxyproline-rich domain was recently shown to contain two types of glycosylation: (1) a large hydroxyproline-linked arabinogalactan composed of a short β1,6-galactan core substituted by a variable number (5–28) of α-arabinofuranose residues forming branched side chains with 5-, 2,5-, 3,5-, and 2,3,5-substituted arabinoses, and (2) single and adjacent β-arabinofuranoses linked to hydroxyproline. As described for other pollen, ragweed and mugwort pollen also contain the pan-allergen profilin and calcium-binding proteins, which are responsible for extensive cross-reactivity among pollen-sensitized patients.

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“…The human MHC on chromosome 6p, particularly HLA (Freidhoff et al 1988;Marsh and Huang 1991;Young et al 1994;Aron et al 1996) and tumor necrosis factor (TNF) locus polymorphism (Campbell et al 1995;Moffatt and Cookson 1997), has also been investigated extensively, as has polymorphism in the 12q15-24 region (Barnes et al 1996;Wilkinson et al 1996). Other candidate genes investigated include, but are not limited to, the ␣ region of the T-Cell Receptor (TCR) ␣/␦ locus (Moffatt et al 1994); the ␣ 1 -Antitrypsin gene (␣ 1 -AT; Katz et al 1976;Hyde et al 1979; Liebermann and Colp 1990); histo-blood-group genetic systems (Kauffmann et al 1996); the cystic fibrosis gene (⌬F508; Mennie et al 1995;Schroeder et al 1995); Gm allotypes of IgG genes (Oxelius 1990); the Ig heavychain ␥ 4 locus (IGHG4; Amoroso et al 1996); the Clara cell-secretory-protein (CC16) locus (Laing et al 1998;Mao et al 1998); the chemokine receptor loci on chromosome 3 (Hall et al 1999;Syed et al 1999); and angiotensin-converting enzyme (ACE) gene (Benessiano et al 1997).…”

Section: Candidate Gene Approachesmentioning

confidence: 99%

Genomic Approaches to Understanding Asthma

Palmer¹,

Cookson²

2000

Genome Res.

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Asthma is the most common chronic childhood disease in developed nations, and it is a complex disease that has high social and economic costs. Asthma and its associated intermediate phenotypes are under a substantial degree of genetic control. The genetic aetiology of asthma offers a means of better understanding its pathogenesis and, thus, improving preventive strategies, diagnostic tools, and therapies. Considerable effort and expense have been expended in attempts to detect genetic loci contributing to asthma susceptibility, and extensive candidate gene studies and a number of whole-genome screens have been undertaken. This article reviews the current state of knowledge of the genetics of asthma, with a focus on genomic approaches to understanding allergic diseases.

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HLA‐DR and HLA‐DP genotypes and immunoglobulin E responses to common major allergens

Cited by 153 publications

References 30 publications

Association between quantitative traits underlying asthma and the HLA-DRB1 locus in a family-based population sample

Association between quantitative traits underlying asthma and the HLA-DRB1 locus in a family-based population sample

The Spectrum of Allergens in Ragweed and Mugwort Pollen

Genomic Approaches to Understanding Asthma

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