Holloway J W, Doull I, Begishvili B, Beasley R, Holgate S T, Howell W M
Malaghan Institute of Medical Research, Wellington School of Medicine, New Zealand.
Clin Exp Allergy. 1996 Oct;26(10):1142-9.
HLA class II genetic polymorphism has been variably implicated in susceptibility to specific immune responsiveness to house dust mite (HDM) allergens, and may also influence the development of atopy.
In order to assess accurately the influence of HLA alleles in the atopic immune response, we typed 22 families selected from 131 previously obtained randomly selected families (i.e. without regard to atopy or asthma), chosen on the basis of two or more members having skin prick reactivity to HDM.
Each individual was fully typed for HLA-DRB1, DQA1, DQB1 and DPB1 class II alleles using a combination of sequence-specific oligonucleotide probes (SSOP) and sequence-specific primer (SSP) polymerase chain reaction (PCR) typing and direct sequencing.
Using appropriate statistical tests, no significant allelic associations were found between any DRB1, DQB1 or DPB1 alleles and atopy or skin prick reactivity to Dermataphagoides pteronyssinus (Der p) or D. farinae (Der f). However, positive associations were found between DQA1*0301 and skin prick reactivity to Der f (P = 0.009) and atopy (P = 0.027). Sib-pair analysis revealed no significant sharing of alleles between affected sib pairs for any of the phenotypes studied.
These results fail to confirm a previously reported association between the DRB1*04 and 07 haplotypes and atopy, and suggest that HLA class II restriction does not play a major role in the development of the IgE response to domestic house dust mite allergens in the British population.
HLA Ⅱ类基因多态性与对屋尘螨(HDM)过敏原的特异性免疫反应易感性存在不同程度的关联,也可能影响特应性的发展。
为了准确评估 HLA 等位基因在特应性免疫反应中的影响,我们对从 131 个先前随机选取的家庭(即不考虑特应性或哮喘)中挑选出的 22 个家庭进行了基因分型,这些家庭是基于有两名或更多成员对 HDM 有皮肤点刺反应而挑选出来的。
使用序列特异性寡核苷酸探针(SSOP)和序列特异性引物(SSP)聚合酶链反应(PCR)分型及直接测序相结合的方法,对每个个体的 HLA - DRB1、DQA1、DQB1 和 DPB1 Ⅱ类等位基因进行全面分型。
通过适当的统计学检验,未发现任何 DRB1、DQB1 或 DPB1 等位基因与特应性或对粉尘螨(Der p)或屋尘螨(Der f)的皮肤点刺反应之间存在显著的等位基因关联。然而,发现 DQA1*0301 与对 Der f 的皮肤点刺反应(P = 0.009)和特应性(P = 0.027)之间存在正相关。同胞对分析显示,在所研究的任何表型中,受影响的同胞对之间等位基因无显著共享。
这些结果未能证实先前报道的 DRB1*04 和 07 单倍型与特应性之间的关联,并表明 HLA Ⅱ类限制在英国人群对家用屋尘螨过敏原的 IgE 反应发展中不发挥主要作用。