Allergy Asthma Immunol Res.  2012 May;4(3):143-149. 10.4168/aair.2012.4.3.143.

The HLA-DRB1 Polymorphism is Associated With Atopic Dermatitis, but not Egg Allergy in Korean Children

Affiliations
  • 1Department of Pediatrics, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea.
  • 2Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. kmaped@skku.edu
  • 3Environmental Health Center for Atopic Diseases, Samsung Medical Center, Seoul, Korea.
  • 4Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea. parkmhee@snu.ac.kr

Abstract

PURPOSE
We investigated whether particular HLA-DRB1 polymorphisms contribute to egg allergy development in Korean children with atopic dermatitis (AD).
METHODS
HLA-DRB1 alleles were determined by PCR-sequence-specific oligonucleotide (SSO) and PCR-single-strand conformation polymorphism (SSCP) methods in 185 patients with AD and 109 normal control (NC) subjects. AD patients were divided into two groups: 1) AD with egg allergy, consisting of 96 patients with egg allergies as determined by egg-specific immunoglobulin E (IgE) reactivity; and 2) AD without egg allergy, consisting of 89 patients without egg allergies. HLA-DRB1 alleles were classified into functional groups (A, De, Dr, E, Q, R, a). HLA-DRB1 phenotype and functional group frequencies in the AD, AD with egg allergy, and AD without egg allergy groups were compared with those in the NC group.
RESULTS
The frequency of DRB1*08:02 was decreased in the AD with egg allergy group compared with the AD without egg allergy group (2.1% vs. 10.1%, P=0.021), and DRB1*15:01 was increased in the AD with egg allergy group compared with the AD without egg allergy group (22.9% vs. 11.2%, P=0.036). However, significance was lost after Bonferroni correction. HLA-DRB1*11:01 had a significantly higher frequency in AD patients compared with NCs (12.4% vs. 1.8%, corrected P=0.048) and was regarded as a susceptibility factor associated with AD. DRB1*08:03 was decreased in AD patients compared with NCs (10.8% vs. 19.3%, P=0.043). HLA-DRB1 functional group 'a', which includes DRB1*15:01, seemed to be associated with the development of egg allergy in AD (P=0.033), but this result was not significant after Bonferroni correction.
CONCLUSIONS
HLA-DRB1 polymorphism is not associated with egg allergy, but HLA-DRB1*11:01 is associated with AD in Korean children.

Keyword

Egg; atopic dermatitis; HLA-DRB1; children; Korean

MeSH Terms

Alleles
Child
Dermatitis, Atopic
Egg Hypersensitivity
HLA-DRB1 Chains
Humans
Immunoglobulin E
Immunoglobulins
Ovum
Phenotype
HLA-DRB1 Chains
Immunoglobulin E
Immunoglobulins

Reference

1. Eigenmann PA, Sicherer SH, Borkowski TA, Cohen BA, Sampson HA. Prevalence of IgE-mediated food allergy among children with atopic dermatitis. Pediatrics. 1998. 101:E8.
2. Guillet G, Guillet MH. Natural history of sensitizations in atopic dermatitis. A 3-year follow-up in 250 children: food allergy and high risk of respiratory symptoms. Arch Dermatol. 1992. 128:187–192.
3. Eggesbø M, Botten G, Halvorsen R, Magnus P. The prevalence of allergy to egg: a population-based study in young children. Allergy. 2001. 56:403–411.
4. Dean T, Venter C, Pereira B, Arshad SH, Grundy J, Clayton CB, Higgins B. Patterns of sensitization to food and aeroallergens in the first 3 years of life. J Allergy Clin Immunol. 2007. 120:1166–1171.
5. Ricci G, Patrizi A, Baldi E, Menna G, Tabanelli M, Masi M. Long-term follow-up of atopic dermatitis: retrospective analysis of related risk factors and association with concomitant allergic diseases. J Am Acad Dermatol. 2006. 55:765–771.
6. Woo JG, Assa'ad A, Heizer AB, Bernstein JA, Hershey GK. The -159 C-->T polymorphism of CD14 is associated with nonatopic asthma and food allergy. J Allergy Clin Immunol. 2003. 112:438–444.
7. Campos E, Shimojo N, Inoue Y, Arima T, Suzuki S, Tomiita M, Matsuura T, Hata A, Suzuki Y, Aoyagi M, Kohno Y. No association of polymorphisms in the 5' region of the CD14 gene and food allergy in a Japanese population. Allergol Int. 2007. 56:23–27.
8. Torgerson TR, Linane A, Moes N, Anover S, Mateo V, Rieux-Laucat F, Hermine O, Vijay S, Gambineri E, Cerf-Bensussan N, Fischer A, Ochs HD, Goulet O, Ruemmele FM. Severe food allergy as a variant of IPEX syndrome caused by a deletion in a noncoding region of the FOXP3 gene. Gastroenterology. 2007. 132:1705–1717.
9. Amoli MM, Hand S, Hajeer AH, Jones KP, Rolf S, Sting C, Davies BH, Ollier WE. Polymorphism in the STAT6 gene encodes risk for nut allergy. Genes Immun. 2002. 3:220–224.
10. Negoro T, Orihara K, Irahara T, Nishiyama H, Hagiwara K, Nishida R, Takagi H, Satoh K, Yamamoto Y, Shimizu S, Hagiwara T, Ishii M, Tanioka T, Nakano Y, Takeda K, Yoshimura I, Iikura Y, Tobe T. Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children. Pediatr Allergy Immunol. 2006. 17:583–590.
11. Kusunoki T, Okafuji I, Yoshioka T, Saito M, Nishikomori R, Heike T, Sugai M, Shimizu A, Nakahata T. SPINK5 polymorphism is associated with disease severity and food allergy in children with atopic dermatitis. J Allergy Clin Immunol. 2005. 115:636–638.
12. Campos Alberto EJ, Shimojo N, Suzuki Y, Mashimo Y, Arima T, Matsuura T, Inoue Y, Yamaide A, Tomiita M, Fujii K, Hata A, Kohno Y. IL-10 gene polymorphism, but not TGF-beta1 gene polymorphisms, is associated with food allergy in a Japanese population. Pediatr Allergy Immunol. 2008. 19:716–721.
13. Liu X, Beaty TH, Deindl P, Huang SK, Lau S, Sommerfeld C, Fallin MD, Kao WH, Wahn U, Nickel R. Associations between specific serum IgE response and 6 variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study. J Allergy Clin Immunol. 2004. 113:489–495.
14. Scherer MN, Graeb C, Tange S, Justl M, Jauch K, Geissler EK. Soluble allogeneic MHC class I molecule gene transfer promotes CTL apoptosis in vivo. Transplant Proc. 2001. 33:583–584.
15. Cardaba B, Cortegano I, Florido F, Arrieta I, Aceituno E, del Pozo V, Gallardo S, Rojo M, Palomino P, Lahoz C. Genetic restrictions in olive pollen allergy. J Allergy Clin Immunol. 2000. 105:292–298.
16. D'Amato M, Picardi A, Menna T, Di Somma C, Ariano R, di Pietro A, Charron D, Maggi E, Matricardi P, Plebani A, Poto S, Testa G, Sacerdoti G, Ruffilli A. HLA-DRB1* and allergy to Parietaria: linkage and association analyses. Hum Immunol. 1999. 60:1250–1258.
17. Sénéchal H, Geny S, Desvaux FX, Busson M, Mayer C, Aron Y, Oster JP, Bessot JC, Peltre G, Pauli G, Swierczewski E. Genetics and specific immune response in allergy to birch pollen and food: evidence of a strong, positive association between atopy and the HLA class II allele HLA-DR7. J Allergy Clin Immunol. 1999. 104:395–401.
18. Stephan V, Kuehr J, Seibt A, Saueressig H, Zingsem S, Dinh TD, Moseler M, Wahn V, Deichmann KA. Genetic linkage of HLA-class II locus to mite-specific IgE immune responsiveness. Clin Exp Allergy. 1999. 29:1049–1054.
19. Blumenthal MN. Positive association between HLA-DRB1*07 and specific IgE responses to purified major allergens of D. pteronyssinus (Der p 1 and Der p 2). Ann Allergy Asthma Immunol. 2002. 88:147–149.
20. Camponeschi B, Lucarelli S, Frediani T, Barbato M, Quintieri F. Association of HLA-DQ7 antigen with cow milk protein allergy in Italian children. Pediatr Allergy Immunol. 1997. 8:106–109.
21. Higgins JA, Lamb JR, Lake RA, O'Hehir RE. Polyclonal and clonal analysis of human CD4+ T-lymphocyte responses to nut extracts. Immunology. 1995. 84:91–97.
22. Hand S, Darke C, Thompson J, Stingl C, Rolf S, Jones KP, Davies BH. Human leucocyte antigen polymorphisms in nut-allergic patients in South Wales. Clin Exp Allergy. 2004. 34:720–724.
23. Rajka G. On definition and framework of atopic dermatitis. Acta Derm Venereol Suppl (Stockh). 1989. 144:10–12.
24. Berth-Jones J. Six area, six sign atopic dermatitis (SASSAD) severity score: a simple system for monitoring disease activity in atopic dermatitis. Br J Dermatol. 1996. 135:Suppl 48. 25–30.
25. Sampson HA. Utility of food-specific IgE concentrations in predicting symptomatic food allergy. J Allergy Clin Immunol. 2001. 107:891–896.
26. Bannai M, Tokunaga K, Lin L, Kuwata S, Mazda T, Amaki I, Fujisawa K, Juji T. Discrimination of human HLA-DRB1 alleles by PCR-SSCP (single-strand conformation polymorphism) method. Eur J Immunogenet. 1994. 21:1–9.
27. Ou D, Mitchell LA, Tingle AJ. A new categorization of HLA DR alleles on a functional basis. Hum Immunol. 1998. 59:665–676.
28. Stern LJ, Brown JH, Jardetzky TS, Gorga JC, Urban RG, Strominger JL, Wiley DC. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature. 1994. 368:215–221.
29. Marsh SG, Albert ED, Bodmer WF, Bontrop RE, Dupont B, Erlich HA, Fernández-Viña M, Geraghty DE, Holdsworth R, Hurley CK, Lau M, Lee KW, Mach B, Maiers M, Mayr WR, Müller CR, Parham P, Petersdorf EW, Sasazuki T, Strominger JL, Svejgaard A, Terasaki PI, Tiercy JM, Trowsdale J. Nomenclature for factors of the HLA system, 2010. Tissue Antigens. 2010. 75:291–455.
30. Ozawa A, Ohkido M, Tsuji K. Some recent advances in HLA and skin diseases. J Am Acad Dermatol. 1981. 4:205–230.
31. Schultz Larsen F, Grunnet N. Genetic investigations in atopic dermatitis. Tissue Antigens. 1987. 29:1–6.
32. Lee HJ, Ha SJ, Han H, Kim JW. Distribution of HLA-A, B alleles and polymorphisms of TAP and LMP genes in Korean patients with atopic dermatitis. Clin Exp Allergy. 2001. 31:1867–1874.
33. Saeki H, Kuwata S, Nakagawa H, Etoh T, Yanagisawa M, Miyamoto M, Tokunaga K, Juji T, Shibata Y. HLA and atopic dermatitis with high serum IgE levels. J Allergy Clin Immunol. 1994. 94:575–583.
34. Svejgaard E, Jakobsen B, Svejgaard A. Studies of HLA-ABC and DR antigens in pure atopic dermatitis and atopic dermatitis combined with allergic respiratory disease. Acta Derm Venereol Suppl (Stockh). 1985. 114:72–76.
35. Howell WM, Holgate ST. HLA genetics and allergic disease. Thorax. 1995. 50:815–818.
36. Boehncke WH, Loeliger C, Kuehnl P, Kalbacher H, Böhm BO, Gall H. Identification of HLA-DR and -DQ alleles conferring susceptibility to pollen allergy and pollen associated food allergy. Clin Exp Allergy. 1998. 28:434–441.
37. Shreffler WG, Charlop-Powers Z, Sicherer SH. Lack of association of HLA class II alleles with peanut allergy. Ann Allergy Asthma Immunol. 2006. 96:865–869.
38. Shinbara M, Kondo N, Agata H, Fukutomi O, Nishida T, Kobayashi Y, Orii T. T cell proliferation restricted by HLA class II molecules in patients with hen's egg allergy. Exp Clin Immunogenet. 1995. 12:103–110.
39. Fu XT, Bono CP, Woulfe SL, Swearingen C, Summers NL, Sinigaglia F, Sette A, Schwartz BD, Karr RW. Pocket 4 of the HLA-DR (alpha, beta 1*0401) molecule is a major determinant of T cells recognition of peptide. J Exp Med. 1995. 181:915–926.
40. Torres-Galván MJ, Quiralte J, Blanco C, Castillo R, Carrillo T, Pérez-Aciego P, Sánchez-García F. Pocket 4 in the HLA-DRB1 antigen-binding groove: an association with atopy. Allergy. 2000. 55:398–401.
41. van Nieuwaal NH, Lasfar W, Meijer Y, Kentie PA, Flinterman AE, Pasmans SG, Knulst AC, Hoekstra MO. Utility of peanut-specific IgE levels in predicting the outcome of double-blind, placebo-controlled food challenges. J Allergy Clin Immunol. 2010. 125:1391–1392.
42. Bernhisel-Broadbent J, Dintzis HM, Dintzis RZ, Sampson HA. Allergenicity and antigenicity of chicken egg ovomucoid (Gal d III) compared with ovalbumin (Gal d I) in children with egg allergy and in mice. J Allergy Clin Immunol. 1994. 93:1047–1059.
43. Cooke SK, Sampson HA. Allergenic properties of ovomucoid in man. J Immunol. 1997. 159:2026–2032.
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