Association of a common dog leucocyte antigen class II haplotype with canine primary immune-mediated haemolytic anaemia

Association of a common dog leucocyte antigen class II haplotype with canine primary immune-mediated haemolytic anaemia
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DOI:
10.1111/j.1399-0039.2006.00715.x
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发表时间:
2006-12-01
期刊:
影响因子:
--
通讯作者:
Day, M. J.
Day, M. J.
中科院分区:
医学4区
文献类型:
--
作者:
Kennedy, L. J.;Barnes, A.;Day, M. J.

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免疫介导的溶血性贫血(IMHA)是犬最常见的免疫介导的疾病,是该物种的主要健康问题。本研究的目的是确定IMHA的遗传易感性是否与犬主要组织相容性复合体(MHC;犬白细胞抗原系统,DLA)的基因相关。从108只患有原发性特发性Coombs阳性IMHA的犬中采集样本。根据Coombs试验结果将该患病人群细分为两组:1)具有显性温反应性免疫球蛋白(IG)G血凝素的犬和(2)具有额外或显性冷反应性IgM血凝素的犬。DLA II类等位基因和单倍型的患病人群进行了表征,这些数据进行了比较,来自品种匹配的对照组和一个更大的DLA型犬组。在患者组中有两种单倍型增加:DLA-DRB 1 *00601/DQA 1 *005011/DQB 1 *00701(仅在热反应性IgG血凝素组中)和DLA-DRB 1 *015/DQA 1 *00601/DQB 1 *00301(在两组中,但在冷反应性IgM血凝素组中更多)。一种单倍型DLA-DRB 1 *001/DQA 1 *00101/DQB 1 *00201在总患者组中减少,但这种减少仅限于热反应性IgG血凝素组,而在冷反应性IgM血凝素组中实际上增加。第二个单倍型DLA-DRB 1 *015/DQA 1 *00601/DQB 1 *02301在总患者组中也减少,并且在两个亚组中均发现这种减少。此外,携带DLA-DRB 1 *001的所有单倍型在冷反应性IgM血凝素组中显著增加。当整个患者组被划分的基础上,个别品种超过6只动物的代表,每一个单倍型可以被证明是牵连的品种之一。因此,很明显,不同的品种具有不同的MHC与犬IMHA的关联,这类似于不同的人类种族群体可以具有不同的HLA与相同的免疫介导的疾病的关联的观察。
Immune-mediated haemolytic anaemia (IMHA) is the commonest immune-mediated disease of the dog, representing a major health concern to this species. The aim of this investigation was to determine whether genetic susceptibility to IMHA is associated with genes of the canine major histocompatibility complex (MHC; dog leucocyte antigen system, DLA). Samples were collected from 108 dogs with primary idiopathic, Coombs' positive IMHA. This diseased population was subdivided on the basis of Coombs' test results into two groups: 1) dogs with dominant warm-reactive immunoglobulin (Ig) G haemagglutinins and (2) dogs with an additional or dominant cold-reactive IgM haemagglutinin. The DLA class II alleles and haplotypes of the diseased population were characterised, and these data were compared with those derived from a breed-matched control cohort and a much larger group of DLA-typed dogs. Two haplotypes were increased in the patient group: DLA-DRB1*00601/DQA1*005011/DQB1*00701 (in the group with warm-reactive IgG haemagglutinins only) and DLA-DRB1*015/DQA1*00601/DQB1*00301 (in both groups, but more so in the group with cold-reactive IgM haemagglutinins). One haplotype, DLA-DRB1*001/DQA1*00101/DQB1*00201, was decreased in the total patient group, but this decrease was limited to the warm-reactive IgG haemagglutinins group, and it was actually increased in the cold-reactive IgM haemagglutinins group. A second haplotype, DLA-DRB1*015/DQA1*00601/DQB1*02301, was also decreased in the total patient group, and this decrease was found in both subgroups. In addition, all haplotypes carrying DLA-DRB1*001 were significantly increased in the cold-reactive IgM haemagglutinins group. When the overall patient group was divided on the basis of individual breeds with more than six animals represented, each of the haplotypes could be shown to be implicated in one of the breeds. Thus, it was apparent that different breeds had different MHC associations with canine IMHA, which is similar to the observation that different human ethnic groups can have different HLA associations with the same immune-mediated disease.