State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Front Immunol. 2023 Jan 30;14:1056381. doi: 10.3389/fimmu.2023.1056381. eCollection 2023.
Activated cytotoxic T cells (CTLs) recognize the auto-antigens presented on hematopoietic stem/progenitor cells (HSPCs) through class I human leukocyte antigen (HLA) molecules and play an important role in the immune pathogenesis of aplastic anemia (AA). Previous reports demonstrated that HLA was related to the disease susceptibility and response to immunosuppressive therapy (IST) in AA patients. Recent studies have indicated that specific HLA allele deletions, which helped AA patients to evade CTL-driven autoimmune responses and escape from immune surveillance, may lead to high-risk clonal evolution. Therefore, HLA genotyping has a particular predictive value for the response to IST and the risk of clonal evolution. However, there are limited studies on this topic in the Chinese population.
To explore the value of HLA genotyping in Chinese patients with AA, 95 AA patients treated with IST were retrospectively investigated.
The alleles HLA-B15:18 and HLA-C04:01 were associated with a superior long-term response to IST (P = 0.025; P = 0.027, respectively), while the allele HLA-B40:01 indicated an inferior result (P = 0.02). The allele HLA-A01:01 and HLA-B54:01 were associated with high-risk clonal evolution (P = 0.032; P = 0.01, respectively), and the former had a higher frequency in very severe AA (VSAA) patients than that in severe AA (SAA) patients (12.7% vs 0%, P = 0.02). The HLA-DQ03:03 and HLA-DR*09:01 alleles were associated with high-risk clonal evolution and poor long-term survival in patients aged ≥40 years. Such patients may be recommended for early allogeneic hematopoietic stem cell transplantation rather than the routine IST treatment.
HLA genotype has crucial value in predicting the outcome of IST and long-term survival in AA patients, and thus may assist an individualized treatment strategy.
细胞毒性 T 细胞（CTLs）通过 I 类人白细胞抗原（HLA）分子识别造血干细胞/祖细胞（HSPCs）上的自身抗原，在再生障碍性贫血（AA）的免疫发病机制中发挥重要作用。先前的报告表明，HLA 与 AA 患者的疾病易感性和对免疫抑制治疗（IST）的反应有关。最近的研究表明，特定的 HLA 等位基因缺失有助于 AA 患者逃避 CTL 驱动的自身免疫反应并逃脱免疫监视，可能导致高风险的克隆进化。因此，HLA 基因分型对 IST 的反应和克隆进化的风险具有特殊的预测价值。然而，在中国人群中，关于这个主题的研究有限。
为了探讨 HLA 基因分型在 AA 中国患者中的价值，回顾性调查了 95 例接受 IST 治疗的 AA 患者。
等位基因 HLA-B15:18 和 HLA-C04:01 与 IST 的长期反应良好相关（P = 0.025；P = 0.027），而等位基因 HLA-B40:01 则结果较差（P = 0.02）。等位基因 HLA-A01:01 和 HLA-B54:01 与高危克隆进化相关（P = 0.032；P = 0.01），前者在极严重 AA（VSAA）患者中的频率高于严重 AA（SAA）患者（12.7%比 0%，P = 0.02）。HLA-DQ03:03 和 HLA-DR*09:01 等位基因与年龄≥40 岁患者的高危克隆进化和长期生存不良相关。对于这些患者，可能建议进行早期异基因造血干细胞移植，而不是常规 IST 治疗。
HLA 基因型在预测 AA 患者 IST 疗效和长期生存方面具有重要价值，因此可能有助于制定个体化治疗策略。
