Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, China.
BGI Genomics, BGI-Shenzhen, Shenzhen, China.
Exp Dermatol. 2020 Jul;29(7):639-646. doi: 10.1111/exd.14127.
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-C07:02 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-C07:02, a haplotype associated with psoriasis, was positively correlated with the diversity of the TCRV gene. Moreover, HLA-C07:02 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-C07:02 were significantly different from those without HLA-C07:02 and without HLA-C06:02. 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.
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要作用。在这里,我们旨在研究银屑病患者 T 细胞受体(TCR)与主要组织相容性复合体(MHC)之间的关系,以进一步了解疾病发病机制中的机制。我们进行了一项横断面研究,涉及 9 对不一致的银屑病双胞胎,并使用多重 PCR 和高通量测序检查了个体的 TCR 多样性和 MHC 单倍型。此外,还应用 665 例银屑病患者验证了人类白细胞抗原(HLA)I 类等位基因 HLA-C07:02 与银屑病的发病年龄或病变严重程度的关系。尽管差异不显著,但与双胞胎中的未受影响个体相比,银屑病患者的免疫多样性较低。具有高 PASI 评分和发病早的银屑病患者的 TCR 克隆型明显减少。与银屑病相关的 HLA-C07:02 单倍型与 TCRV 基因的多样性呈正相关。此外,HLA-C07:02 在 PASI 高和发病早的患者中聚集。在复制阶段,我们发现 HLA-C07:02 阳性银屑病患者的 PASI 和发病年龄与 HLA-C07:02 阴性和 HLA-C06:02 阴性患者明显不同。我们的观察结果表明,HLA-C*07:02 与银屑病 TCRV 基因的多样性呈正相关,可能是银屑病发病早/病变严重的潜在生物标志物。