Behçet disease, new insights in disease associations and manifestations: a next-generation sequencing study.
Behçet disease, new insights in disease associations and manifestations: a next-generation sequencing study.
复制标题
白塞病，疾病关联和表现的新见解：下一代测序研究。
DOI：
10.1111/cei.13571
复制
发表时间：
2021
影响因子：
4.6
通讯作者：
Elfishawi,S
中科院分区：
文献类型：
--
作者：
Elfishawi,M;Mossallam,G;Augusto,DG;Montero-Martin,G;deBruin,H;VandePasch,L;Norman,PJ;Rozemuller,E;Fernandez-Vina,M;Abrudescu,A;Hollenbach,JA;Zaky,K;Elfishawi,S
白塞病是一种与人类白细胞抗原（HLA）I类多态性相关的多系统疾病。高分辨率下一代测序（NGS）与单倍型分析尚未进行这种疾病以前。根据国际研究组（ISG）的标准诊断为白塞病的60名埃及患者和160名健康的地理和种族匹配的对照进行HLA I类基因座（HLA-A，B，C）的基因分型。对于HLA II类基因座（DRB 1、DRB 3/4/5、DQA 1、DQB 1、DPA 1、DPB 1），40个对照样品进行基因分型。使用NGS进行高分辨率HLA基因分型，并对结果进行分析。临床表现为口腔溃疡（100%）、生殖器溃疡（100%）、眼部溃疡（55%）、神经系统溃疡（28%）和血管病变（35%）。HLA-B*51：08 [比值比（OR）= 19·75，95%置信区间（CI）= 6·5-79;P< 0·0001]，HLA-B*15：03（OR = 12.15，95%CI = 3.7 ~ 50.7;P<0.0001），HLA-C*16：02（OR = 6.53，95%CI = 3-14;P<0.0001），HLA-A*68：02（OR = 3·14，95%CI = 1·1-8·9;P< 0·01）与白塞病相关，HLA-DRB 1 *13也是如此：HLA-DQB 1 *06：03与HLA-DQB 1 *06：01比较，差异有统计学意义（OR = 3.39，95%CI = 0.9 ~ 18.9;P= 0.04）。而HLA-A*03：01（OR = 0.13，95%CI = 0 ~ 0.8;P= 0.01）和HLA-DPB 1 *17：01（OR = 0.27，95%CI = 0.06 ~ 1.03;P= 0.02）则具有保护作用。我们在与白塞病相关的单倍型中发现了HLA-B*51：08和C*16：02和A*02：01之间的强连锁不平衡。HLA-B*51：08与法律的盲显著相关（OR = 2.98，95%CI = 1.06 ~ 8.3;P= 0.01）。在埃及白塞病患者中，HLA-B*51：08是最常见的易感等位基因，对眼部受累预后不良。
Behçet disease is a multi-system disease associated with human leukocyte antigen (HLA) class I polymorphism. High-resolution next-generation sequencing (NGS) with haplotype analysis has not been performed previously for this disease. Sixty Egyptian patients diagnosed according to the International Study Group (ISG) criteria for Behçet disease and 160 healthy geographic and ethnic-matched controls were genotyped for HLA class I loci (HLA-A, B, C). For HLA class II loci (DRB1, DRB3/4/5, DQA1, DQB1, DPA1, DPB1), 40 control samples were genotyped. High-resolution HLA genotyping was performed using NGS and the results were analyzed. Clinical manifestations were oral ulcers (100%), genital ulcers (100%), eye (55%) and neurological (28%) and vascular involvement (35%). HLA-B*51:08 [odds ratio (OR) = 19·75, 95% confidence interval (CI) = 6·5–79;P< 0·0001], HLA-B*15:03 (OR = 12·15, 95% CI = 3·7–50·7;P< 0·0001), HLA-C*16:02 (OR = 6·53, 95% CI = 3–14;P< 0·0001), HLA-A*68:02 (OR = 3·14, 95% CI = 1·1–8·9;P< 0·01) were found to be associated with Behçet disease, as were HLA-DRB1*13:01 and HLA-DQB1*06:03 (OR = 3·39, 95% CI = 0·9–18·9;P= 0·04 for both). By contrast, HLA-A*03:01 (OR = 0·13, 95% CI = 0–0·8;P= 0·01) and HLA-DPB1*17:01 were found to be protective (OR = 0·27, 95% CI = 0·06–1·03;P= 0·02). We identified strong linkage disequilibrium between HLA-B*51:08 and C*16:02 and A*02:01 in a haplotype associated with Behçet disease. HLA-B*51:08 was significantly associated with legal blindness (OR = 2·98, 95% CI = 1·06–8·3;P= 0·01). In Egyptian Behçet patients, HLA-B*51:08 is the most common susceptibility allele and holds poor prognosis for eye involvement.