Cross-sectional study reveals that HLA-C*07:02 is a potential biomarker of early onset/lesion severity of psoriasis
Cross-sectional study reveals that HLA-C*07:02 is a potential biomarker of early onset/lesion severity of psoriasis
复制标题
横断面研究表明 HLA –C07:02 是银屑病早期发病/病变严重程度的潜在生物标志物
DOI：
10.1111/exd.14127
复制
发表时间：
2020-07-01
影响因子：
3.6
通讯作者：
Zhang, Kaiming
中科院分区：
文献类型：
--
作者：
Li, Junqin;Li, Xiaofang;Zhang, Kaiming
银屑病是一种常见的慢性自身免疫性皮肤病，T细胞在其发病机制中起主导作用。本研究旨在探讨银屑病患者T细胞亚群（TCR）和主要组织相容性复合体（MHC）的关系，以进一步了解银屑病的发病机制。我们进行了一项横断面研究，涉及9对单卵双胞胎与不一致的银屑病和检查TCR多样性和MHC单倍型的个人使用多重PCR和高通量测序。同时对665例银屑病患者进行了人类白细胞抗原（HLA）Ⅰ类等位基因HLA-C*07：02与银屑病早期发病及皮损严重程度的关系研究。双胞胎中银屑病患者的免疫多样性低于未受影响的个体，尽管差异不显著。PASI评分高、发病早的银屑病患者TCR克隆型明显减少。HLA-C*07：02是银屑病的单倍型，与TCRV基因的多样性呈正相关。此外，HLA-C*07：02聚集在高PASI和早发患者中。在复制阶段，我们发现HLA-C*07：02与无HLA-C * 07：02和无HLA-C*06：02的银屑病患者的PASI和发病年龄有显著差异。提示HLA-C*07：02与银屑病患者TCRV基因多态性呈正相关，可能是银屑病早发/严重病变的潜在生物标志物。
Psoriasis is a common chronic autoimmune skin disease, with T cells playing a predominant role in its pathogenesis. Here, we aimed to investigate the relation of T-cell repertoires (TCR) and major histocompatibility complex (MHC) in psoriatic patients to further understand mechanisms in disease pathogenesis. We conducted a cross-sectional study involving nine pairs of monozygotic twins with inconsistent psoriasis and examined the TCR diversity and MHC haplotype of the individuals using multiple-PCR and high-throughput sequencing. Additionally, 665 psoriatic patients were applied to validate the relation of human leucocyte antigen (HLA) class I allele HLA-C*07:02 and early onset or lesion severity of psoriasis. The immune diversity was lower in psoriatic patients compared with unaffected individuals within the twin pairs, although the difference was not significant. The clonotypes of TCR significantly decreased in psoriatic patients with high PASI score and early onset. HLA-C*07:02, a haplotype associated with psoriasis, was positively correlated with the diversity of the TCRV gene. Moreover, HLA-C*07:02 clustered in patients with high PASI and early onset. In the replication stage, we found that the PASI and onset age in psoriasis with HLA-C*07:02 were significantly different from those without HLA-C*07:02 and without HLA-C*06:02. Our observations indicate that HLA-C*07:02 is positively correlated with the diversity of TCRV gene in psoriasis and maybe a potential biomarker of early onset/severe lesions of psoriasis.