臨床検査49巻7号

2005年07月発行

今月の主題 アレルギー疾患の現況と今後の展望 総説

アレルギー疾患の疫学とメカニズム

著者： 鈴木雅雄¹ 程雷² 小野直哉¹ 山崎暁子¹ 毛暁全² 白川太郎¹

所属機関： ¹京都大学大学院医学研究科健康要因学講座健康増進・行動学分野 ²南京医科大学国際鼻アレルギーセンター疫学・分子アレルギー学部門

ページ範囲：P.700 - P.706

〔SUMMARY〕　近年，先進国で増加しているアレルギー疾患のメカニズムの1つにTh1/Th2バランスの不均衡が関与していることがいわてれおり，特にTh2型サイトカインが重要な役割を果たす．また，その疾患感受性遺伝子を同定することは治療や予防に有益と考えられている．このような，アレルギー疾患は多因子疾患であるため，数多くの遺伝因子と環境要因が複雑に絡み合って発症すると考えられており，これら遺伝的要因の解明は，以前は不可能と思われていた．しかし近年，高速大量タイピング法の確立により広範囲な候補領域からの絞り込みが非常に簡易になり，急速に各アレルギー疾患のSNPマップを用いた体系的症例―対照相関解析によりアレルギー疾患の原因が解明されつつある．今回はこれまで報告されてきた疫学調査を中心に解説したい．〔臨床検査　49：700-706，2005〕

参考文献

１) Taylor B, Wadsworth J, Wadsworth M, et al：Changes in the reported prevalence of childhood eczema since the 1939-1945 war. Lancet　324：1255-1257, 1984

２) Fleming DM, Crombie DL：Prevalence of asthma and fever in England and Wales. BMJ　31：279-283, 1987

３) Nakagomi T, Itaya H, Tominaga T, et al：Is atopy increasing? Lancet　343：121-122, 1994

４) Aberg N, Hesselmar B, Aberg B, et al：Increase of asthma, allergic rhinitis and eczema in Swedish schoolchildren between 1979 and 1991. Clin Exp Allergy　25：815-819, 1995

５) Butland BK, Strachan DP, Lewis S, et al：Investigation into the increase in hay fever and eczema at age 16 observed between the 1958 and 1970 British birth cohorts. BMJ　315：717-721, 1997

６) von Mutius E, Weiland SK, Fritzsch C, et al：Increasing prevalence of hay fever and atopy among children in Leipzig, East Germany. Lancet　351：862-866, 1998

７) Weiland SK, von Mutius E, Hirsch T, et al：Prevalence of respiratory and atopic disorders among children in the East and West of Germany five years after unification. Eur Respir J　14：862-870, 1999

８) Weinberg EG：Urbanization and childhood asthma：an African perspective. J Allergy Clin Immunol　105：224-231, 2000

９) Soto-Quiros ME, Soto-Martinez M, Hanson LA：Epidemiological studies of the very high prevalence of asthma and related symptoms among school children in Costa Rica from 1989 to 1998. Pediatr Allergy Immunol　13：342-349, 2002

10) Busse WW, Lemanske RF Jr：Asthma. N Engl J Med　344：350-362, 2001

11) Strachan DP：Hay fever, hygiene, and household size. BMJ　299：1259-1260, 1989

12) Braun-Fahrlander C, Riedler J, Herz U, et al：Environmental exposure to endotoxin and its relation to asthma in school-age children. N Engl J Med　347：869-877, 2002

13) Shirakawa T, Enomoto T, Shimazu S, et al：The inverse association between tuberculin responses and atopic disorder. Science　275：77-79, 1997

14) Mosmann TR, Sad S：The expanding universe of T-cell subsets：Th1, Th2 and more. Immunol Today　17：138-146, 1996

15) Von Mutius E, Pearce N, Beasey R, et al：International patterns of tuberculosis and the prevalence of symptoms of asthma, rhinitis, and eczema. Thorax　55：449-453, 2000

16) Aaby P, Shaheen SO, Heyes CB, at al：Early BCG Vaccination and reduction in atopy in Guinea-Bissau. Clin Exp Allergy　30：644-650, 2000

17) Stene LC, Nafstad P：Relation between occurrence of type 1 diabetes and asthma. Lancet　357：607-608, 2001

18) Sakaguchi S：Naturally arising CD4＋regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol　22：531-562, 2004

19) Bjorksten B, Sepp E, Julge K, et al：Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol　108：516-520, 2001

20) Kimura M, Koseki Y, Yamashita M, et al：Regulation of Th2 cell differentiation by mel-18, a mammalian poly comb group gene. Immunity　15：275-287, 2001

21) Zhang Y, Leaves NI, Anderson GG, et al：Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma. Nat Genet　34：181-186, 2003

22) Eder W, Klimecki W, Yu L, et al：Toll-like receptor 2 as a major gene for asthma in children of European farmers. J Allergy Clin Immunol　113：482-488, 2004

23) Fageras Bottcher M, Hmani-Aifa M, et al：A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children. J Allergy Clin Immunol　114：561-567, 2004

24) Werner M, Topp R, Wimmer K, et al：TLR4 gene variants modify endotoxin effects on asthma. J Allergy Clin Immunol　112：323-330, 2003

25) Noguchi E, Nishimura F, Fukai H, et al：An association study of asthma and total serum immunoglobin E levels for Toll-like receptor polymorphisms in a Japanese population. Clin Exp Allergy　34：177-183, 2004

26) Lauener RP, Birchler T, Adamski J, et al：Expression of CD14 and Toll-like receptor 2 in farmers’ and non-farmers’ children. Lancet　360：465-466, 2002

27) Sigurs N, Bjarnason R, Sigurbergsson F, et al：Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med　161：1501-1507, 2001

28) Wills-Karp M, Santeliz J, Karp CP：The germ-less theory of allergic disease：revisiting the hygiene hypothesis. Nat Vev Immunol　1：69-75, 2001

29) Fukuda S, Ishikawa H, Koga Y, et al：Allergic symptoms and microflora in schoolchildren. J Adolesc Health　35：156-158, 2004