Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.
Ann Hematol. 2024 Jun;103(6):1897-1907. doi: 10.1007/s00277-024-05740-w. Epub 2024 Apr 15.
Glycosylphosphatidylinositol-anchored protein-deficient hematopoietic stem and progenitor cell development caused by PIGA mutations cannot fully explain the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH). Herein, patients newly diagnosed with PNH at our hospital between April 2019 and April 2021 were recruited. The human leukocyte antigen (HLA) class I and II loci were analyzed, and patients were stratified by PNH clone sizes: small (< 50%) and large (≥ 50%). In 40 patients (29 males; 72.5%), the median PNH clone size was 72%. Thirteen (32.5%) and twenty-seven (67.5%) patients harbored small and large PNH clones, respectively. DRB115:01 and DQB106:02 had higher frequencies in patients with PNH than in healthy controls (adjusted P-value = 4.10 × 10 and 4.10 × 10, respectively). Whole HLA class I and II allele contributions differed (P = 0.046 and 0.065, not significant difference) when comparing patients with small and large PNH clones. B13:01 and C04:01 allelic frequencies were significantly higher in patients with small clones (P = 0.032 and P = 0.032, respectively). Patients with small clones had higher class II HLA evolutionary divergence (HED) (P = 0.041) and global class I and II HED (P = 0.019). In the entire cohort, 17 HLA aberrations were found in 11 (27.5%) patients. No significant differences in HLA aberrations were found between patients with small or large clones. In conclusion, patients with small clones tended to have a higher frequency of immune attack-associated alleles. A higher HED in patients with small clones may reflect a propensity for T cell-mediated autoimmunity. HLA aberrations were similar between patients with small and large clones.
糖基磷脂酰肌醇锚定蛋白缺陷的造血干细胞和祖细胞发育障碍是阵发性睡眠性血红蛋白尿症（PNH）发病机制的重要原因之一，但 PIGA 突变尚不能完全解释 PNH 的发病机制。本研究纳入了 2019 年 4 月至 2021 年 4 月在我院新诊断为 PNH 的患者。分析了人类白细胞抗原（HLA）I 类和 II 类基因座，并根据 PNH 克隆大小进行分层：小（<50%）和大（≥50%）。在 40 例患者（29 例男性；72.5%）中，PNH 克隆的中位数为 72%。13 例（32.5%）和 27 例（67.5%）患者分别携带小和大 PNH 克隆。与健康对照组相比，DRB115:01 和 DQB106:02 在 PNH 患者中的频率更高（校正 P 值分别为 4.10×10 和 4.10×10）。比较小和大 PNH 克隆患者时，全 HLA I 类和 II 类等位基因贡献不同（P=0.046 和 0.065，无显著性差异）。B13:01 和 C04:01 等位基因频率在小克隆患者中显著升高（P=0.032 和 P=0.032）。小克隆患者的 II 类 HLA 进化分歧（HED）更高（P=0.041），全 I 类和 II 类 HLA HED 也更高（P=0.019）。在整个队列中，11 例（27.5%）患者发现了 17 种 HLA 异常。小或大克隆患者的 HLA 异常无显著差异。总之，小克隆患者倾向于具有更高频率的与免疫攻击相关的等位基因。小克隆患者的 HED 较高可能反映了 T 细胞介导自身免疫的倾向。小和大克隆患者的 HLA 异常相似。
