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寡核苷酸分型显示,I 型银屑病与 HLA-DRB1*0701/2、-DQA1*0201、-DQB1*0303 扩展单倍型相关。

Oligonucleotide typing reveals association of type I psoriasis with the HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 extended haplotype.

作者信息

Schmitt-Egenolf M, Boehncke W H, Ständer M, Eiermann T H, Sterry W

机构信息

Department of Dermatology, University of Ulm, Germany.

出版信息

J Invest Dermatol. 1993 Jun;100(6):749-52. doi: 10.1111/1523-1747.ep12476080.

Abstract

Although the pathogenesis of psoriasis is still a matter of debate, there are several lines of evidence supporting the concept of this disease being immunologically mediated with T cells playing a crucial role. Because a considerable portion of the cellular infiltrate in psoriasis consists of activated T-helper cells, expression of HLA class II antigens might be of particular importance for the understanding of its pathogenesis. Therefore, we investigated the HLA type of patients with type I (early onset, positive family history) and type II (late onset, no family history) psoriasis by means of serology (n = 89) and genotyping using sequence-specific oligonucleotide probes (n = 64). Serologic analysis of class I documented the association of type I psoriasis with HLA-Cw6, -B13, and -B57, whereas type II psoriasis showed a weaker correlation with HLA-Cw2 and -B27. Genotyping using SSO for class II detected the elevation of the HLA-DRB10701/2 allele frequency from 13% in normal population to 36% in type I, but only to 15% in type II psoriatics. Moreover, positive correlations with type I psoriasis were detected for HLA-DQA10201 and HLA-DQB10303. The HLA-DRB10701/2, -DQA10201, -DQB10303 extended haplotype was found exclusively in type I psoriasis. This is the first report documenting the association of distinct HLA class II alleles with type I psoriasis as detected on the DNA level, an approach both more specific and more sensitive when compared to serology.

摘要

尽管银屑病的发病机制仍存在争议,但有几条证据支持这种疾病是由免疫介导的,T细胞起着关键作用这一概念。因为银屑病中相当一部分细胞浸润由活化的辅助性T细胞组成,所以HLA II类抗原的表达对于理解其发病机制可能尤为重要。因此,我们通过血清学方法(n = 89)和使用序列特异性寡核苷酸探针的基因分型方法(n = 64)研究了I型(早发型,家族史阳性)和II型(晚发型,无家族史)银屑病患者的HLA类型。I类的血清学分析证明I型银屑病与HLA-Cw6、-B13和-B57相关,而II型银屑病与HLA-Cw2和-B27的相关性较弱。使用序列特异性寡核苷酸探针(SSO)对II类进行基因分型检测到HLA-DRB10701/2等位基因频率从正常人群的13%升高到I型银屑病患者的36%,但在II型银屑病患者中仅升高到15%。此外,还检测到HLA-DQA10201和HLA-DQB10303与I型银屑病呈正相关。HLA-DRB10701/2、-DQA10201、-DQB10303扩展单倍型仅在I型银屑病中发现。这是第一份记录在DNA水平上检测到的不同HLA II类等位基因与I型银屑病之间关联的报告,与血清学相比,这种方法更具特异性和敏感性。

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