湖北漢族人群對(duì)乙肝疫苗免疫應(yīng)答的水平與HLA-I類分子多態(tài)性的相關(guān)研究

1、湖北漢族人群對(duì)乙肝疫苗免疫應(yīng)答的水平與HLA-I類分子多態(tài)性的相關(guān)研究    涂正坤吳雄文劉敏姜曉丹楊志章吳鋒龔非力趙修竹中國(guó)圖書分類號(hào)R392.11R394.5R311.144R730.3摘要目的：探討人群對(duì)乙肝疫苗免疫應(yīng)答與HLA遺傳多態(tài)性的相關(guān)性。方法：對(duì)52名湖北漢族健康自愿者進(jìn)行HBV血源疫苗標(biāo)準(zhǔn)全程接種，共3次(第0、1、6月)，末次接種后8 w用酶免疫法(EIA)檢測(cè)血清抗HBs抗體水平：S/N2.1為應(yīng)答者；S/N2.1為無(wú)應(yīng)答者。同時(shí)對(duì)受試者進(jìn)行HLA-I類抗原多態(tài)性檢測(cè)。結(jié)果：應(yīng)答者42人(81.0%)，無(wú)應(yīng)答者10人(19.0%)；

2、無(wú)應(yīng)答者與HLA-B39具有顯著相關(guān)性，RR17.5，25.22，P0.05，而與HLA-B62呈負(fù)相關(guān)，26.41，P0.05。結(jié)論：在湖北漢族人群中，HLA-B39表型陽(yáng)性個(gè)體對(duì)乙肝疫苗免疫應(yīng)答水平明顯低于其他個(gè)體，而HLA-B62表型陽(yáng)性個(gè)體明顯高于其他個(gè)體。關(guān)鍵詞人類白細(xì)胞抗原乙肝疫苗免疫應(yīng)答Association between the feature of the immune response to hepatitis B vaccine and HLA class I polymorphism in a Hubei population of the Han nationali

3、tyTU Zheng-Kun ，WU Xiong-Wen， LIU Min et al. Department of Immunology,Tongji Medical University,Wuhan 430030AbstractObjective:To study association between the feature of the immune response to hepatitis B vaccine and HLA genetic polymorphism on human.Methods:52 healthy volunteers of the Han national

4、ity from Hubei province were subjected to a standard course of immunization with HBV plasma vaccine at month 0,1 and 6 successively. 8 weeks after the last immunization,serum level of anti-HBs antibody were assayed with EIA.Individuals with S/N2.1 are responders,and S/N2.1 are nonresponders. Results

5、:42(81.0%) of the 52 subjects were responders,10(19.0%) individuals were nonresponders.Unresponsiveness of the 10 individuals to hepatitis B vaccine were found to be positively associated with HLA-B39(RR17.5,2=5.22,P0.05) and negatively associated with HLA-B62(2=6.41,P0.05),as demonstrated by HLA-I

6、antigen polymorphism analysis.Conclusion:The level of immune response to hepatitis B vaccine of individuals bearing HLA-B39 antigen was significantly lower than others,individuals bearing HLA-B62 antigen was significantly higher than others.Key wordsHLAHepatitis B vaccineImmune response乙肝疫苗是取自慢性乙型肝炎

7、病毒(HBV)攜帶者血液、通過滅活并純化的乙肝表面抗原(HBsAg)，它的問世為乙型肝炎的預(yù)防提供了有力的武器，使乙型肝炎及其續(xù)發(fā)癥(慢性肝炎、肝硬化和原發(fā)性肝癌等)得到了有效的控制。但并非所有接種乙肝疫苗者均能免遭HBV感染，人群對(duì)乙肝疫苗的免疫應(yīng)答存在明顯的個(gè)體差異，據(jù)此可將接種人群分為應(yīng)答者和無(wú)應(yīng)答者。影響個(gè)體對(duì)乙肝疫苗應(yīng)答能力的因素包括年齡、性別、疫苗的品牌、是否吸煙、HLA型別等，其中HLA在人類對(duì)乙肝疫苗的免疫應(yīng)答中起重要作用。研究無(wú)應(yīng)答人群的免疫遺傳學(xué)背景，將有助于進(jìn)一步完善無(wú)應(yīng)答人群的HBV預(yù)防對(duì)策，也有助于進(jìn)一步闡明人類免疫應(yīng)答基因(Ir gene)的生物學(xué)意義。本課題選擇湖

8、北漢族人群進(jìn)行乙肝疫苗標(biāo)準(zhǔn)全程接種，觀察其應(yīng)答水平，并分析該組人群HLA-I類表型頻率，以探討無(wú)應(yīng)答人群與HLA-I類抗原多態(tài)性的關(guān)聯(lián)情況。2結(jié)果52名受試者HLA-I類分型結(jié)果和抗HBs抗體水平見表1。52例中無(wú)應(yīng)答者為10名(19.0%)，應(yīng)答者為42名(81.0%)。HLA-I類抗原型別與乙肝疫苗無(wú)應(yīng)答的相關(guān)性見表2。10名無(wú)應(yīng)答者中攜帶HLA-B39表型者為3人，其比例明顯高于應(yīng)答者(42人)中攜帶HLA-B39表型者(1人，2=5.22，P0.05，RR=17.5)。42名應(yīng)答者中攜帶HLA-B62表型者為14人，而10名無(wú)應(yīng)答者中無(wú)一人攜帶HLA-B62(2=6.41，P0.05)

9、。此外，HLA-A2、A24、B16、B17、B40、B46等表型與乙肝疫苗免疫應(yīng)答無(wú)明顯關(guān)聯(lián)。其他HLA型別由于在本實(shí)驗(yàn)中檢出的頻率較低，無(wú)統(tǒng)計(jì)學(xué)意義。      表1湖北漢族人群52名個(gè)體HLA-I類分子多態(tài)性和抗HBs抗體水平Tab.1HLA class I phenotype and level of anti-HBs antibody in 52 individuals tested in this study Specimen ID HLA-I phenotype Level of anti-HbsAb Specimen ID HL

10、A-I phenotype Level of anti-HbsAb A B OD S/N A B OD S/N D409 A1 A2 B5 B62 0.49 5.76 D4371) A2 A10 B39 0.16 1.88 D4101) A2 B12 B39 0.13 1.52 D438 A2 2.69 31.64 D411 A2 3.00 35.29 D439 A10 B35 3.32 39.05 D412 A25 B53 1.60 18.82 D4411) A10 B40B17 0.13 1.52 D4131) A2A24 B16B46 0.14 1.64 D442 A2A10 B40 1

11、.37 16.11 D414 A2A10 B40B62 2.21 26.00 D443 A2A10 B46 0.19 2.23 D417 A2 B46B17 0.18 2.11 D444 A2A11 B62 0.28 3.29 D4181) A2 B16B13 0.09 1.05 D446 A11A2 B12B5 2.47 29.05 00D419 A10A24 B62 2.73 32.11 D447 A2A11 B5B46 1.78 20.94 D420 A2 2.36 27.76 D548 A2 B5 2.84 33.41 D421 B5 3.32 39.05 D549 A2 B62 1.

12、07 12.58 D4221) A33 B17 0.15 1.76 D550 A2 B16B27 0.78 9.17 D423 A10 0.44 5.17 D551 A2 B16B13 3.19 37.52 D424 A25 B7B14 1.21 14.23 D5521) A9 B39B27 0.15 1.76 D425 A2 B46 0.19 2.23 D553 A2 B13B46 2.43 28.58 D426 A2A25 B62 0.33 3.88 D554 A2 B46 0.54 6.35 D427 A33A25 B46B17 1.22 14.35 D555 A2 B62 2.79 3

13、2.87 D428 A1A2 B46B62 0.42 4.94 D556 A2 B46 0.29 3.41 D429 A1A2 B7B62 0.78 9.17 D5571) A11 B5B40 0.15 1.76 D430 A10 B40 1.46 17.17 D558 A24 B40B46 3.04 35.76 D431 A28 B35 3.32 39.05 D5591) A2 B5 0.15 1.76 D4321) A24A25 B46 0.11 1.29 D560 A9 B40 0.20 2.35 D433 A2 B46 3.32 39.05 D561 A9A10 B62B40 0.32

14、 3.76 D434 A2 B5B15 3.20 37.64 D561 A9A10 B62B40 0.32 3.76 D435 B35B12 2.19 25.76 D563 A2A33 B62 1.08 12.70 D436 A2 B62 2.58 30.35 D564 A2A33 B62 2.53 29.76 HLA-phenotype Nonresponders Responders P B39 3 1 0.05 B62 0 14 0.05 B16 2 2 N.s B46 2 11 N.s B17 2 2 N.s B40 2 6 N.s A2 5 25 N.s A24 2 2 N.s No

15、te:N.s:not significant4參考文獻(xiàn)1Milich D R,Leroux-Roels G G,Chisari I V.Genetic regulation of the immune response to the hepatitis B surface antigen (HBsAg) ，qualiative characteristic of the humoral immune response to the a，d and y determinates of HBsAg .J Immunol,1983;130:13952Milich D R， Leroux-Roels

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17、an R E. Alterations in the immune response in nonresponders to the hepatitis B vaccine. J Infect Dis,1985;152:12454Watanabe H， Matsushita S， Nobuhiro K et al. Immunosuppressor gene on HLA-Bw54,DR4,DRw53 haplotype controls nonresponsiveness in humans to hepatitis B surface antigen via CD8+suppressor

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