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Comparison of human leukocyte antigen in patients with paroxysmal nocturnal hemoglobinuria of different clone sizes

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Abstract

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. DRB1*15:01 and DQB1*06:02 had higher frequencies in patients with PNH than in healthy controls (adjusted P-value = 4.10 × 10–4 and 4.10 × 10–4, 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. B*13:01 and C*04:01 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.

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Data availability

The datasets are not publicly available for personal data protection reasons, but are available from the corresponding author upon reasonable request.

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Funding

This study was supported by funding from the National Natural Science Foundation (82370121), Beijing Natural Science Foundation (2023) (7232109), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-026, 2022-PUMCH-D-002, 2022-PUMCH-B-046), and the CAMS Innovation Fund for Medical Sciences (2023-12M-C&T-B-013).

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  1. Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China

    Zhuxin Zhang, Qinglin Hu, Chen Yang, Miao Chen & Bing Han

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Contributions

Zhuxin Zhang: Data curation, Formal analysis, Investigation; Writing the original draft, Writing the review, and Editing.

Qinglin Hu: Data curation; Formal analysis; Investigation.

Chen Yang: Conceptualization; Resources.

Miao Chen: Conceptualization; Resources.

Bing Han: Conceptualization; Funding acquisition, Methodology; Resources; Supervision; Validation.

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Correspondence to Miao Chen or Bing Han.

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Zhang, Z., Hu, Q., Yang, C. et al. Comparison of human leukocyte antigen in patients with paroxysmal nocturnal hemoglobinuria of different clone sizes. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05740-w

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