Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype.
Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype.
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DOI：
10.1186/s13075-015-0640-3
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发表时间：
2015-05-07
影响因子：
4.9
通讯作者：
Winchester R
中科院分区：
文献类型：
--
作者：
FitzGerald O;Haroon M;Giles JT;Winchester R
本文综述了银屑病关节炎（PsA）的遗传特征及其与该病表型异质性的关系，并提出了三个问题：最近人类白细胞抗原（HLA）的研究如何揭示皮肤银屑病（PsO）与PsA之间的遗传关系，即PsO是单一表型吗？PsA是基因异质还是同质的实体；决定PsA易感性的遗传因素是否能预测临床表型？我们首先讨论比较两个PsO队列的HLA分型结果：一个队列提供皮肤病学观点，由无关节炎疾病证据的PsO患者组成；第二组提供风湿病学视角，由PsA患者组成。我们发现这两个队列的主要HLA等位基因差异很大，这表明PsO整体表型存在异质性。此外，PsA队列患者的基因型具有异质性，HLA-B*08、HLA-C*06:02、HLA-B*27、HLA-B*38和HLA-B*39单倍型的频率显著升高。由于不同的遗传易感基因意味着不同的疾病机制，可能不同的临床过程和治疗反应，因此我们回顾了遗传不同HLA等位基因的PsA患者之间表型差异的证据。我们提供的证据表明，决定PsA易感性的不同等位基因，更重要的是，不同的单倍型与不同的表型特征相关，这些特征似乎是亚表型。本文讨论了这些发现对PsA的整体病理生理机制的影响，并具体讨论了PsA是被定义为自身免疫过程还是基于内皮反应的过程。
This review focuses on the genetic features of psoriatic arthritis (PsA) and their relationship to phenotypic heterogeneity in the disease, and addresses three questions: what do the recent studies on human leukocyte antigen (HLA) tell us about the genetic relationship between cutaneous psoriasis (PsO) and PsA – that is, is PsO a unitary phenotype; is PsA a genetically heterogeneous or homogeneous entity; and do the genetic factors implicated in determining susceptibility to PsA predict clinical phenotype? We first discuss the results from comparing the HLA typing of two PsO cohorts: one cohort providing the dermatologic perspective, consisting of patients with PsO without evidence of arthritic disease; and the second cohort providing the rheumatologic perspective, consisting of patients with PsA. We show that these two cohorts differ considerably in their predominant HLA alleles, indicating the heterogeneity of the overall PsO phenotype. Moreover, the genotype of patients in the PsA cohort was shown to be heterogeneous with significant elevations in the frequency of haplotypes containing HLA-B*08, HLA-C*06:02, HLA-B*27, HLA-B*38 and HLA-B*39. Because different genetic susceptibility genes imply different disease mechanisms, and possibly different clinical courses and therapeutic responses, we then review the evidence for a phenotypic difference among patients with PsA who have inherited different HLA alleles. We provide evidence that different alleles and, more importantly, different haplotypes implicated in determining PsA susceptibility are associated with different phenotypic characteristics that appear to be subphenotypes. The implication of these findings for the overall pathophysiologic mechanisms involved in PsA is discussed with specific reference to their bearing on the discussion of whether PsA is conceptualised as an autoimmune process or one that is based on entheseal responses.
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影响因子：
5.5
作者：
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通讯作者：
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通讯作者：
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通讯作者：
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通讯作者：
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