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Research ArticleOriginal Article
Open Access

The immunologic abnormalities in patients with paroxysmal nocturnal hemoglobinuria are associated with disease progression

Guanrou Wang, Mengting Che, Lijie Zeng, Hui Liu, Liyan Li, Zhaoyun Liu and Rong Fu
Saudi Medical Journal April 2024, 45 (4) 424-432; DOI: https://doi.org/10.15537/smj.2024.45.4.20231010
Guanrou Wang
From the Department of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China.
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Mengting Che
From the Department of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China.
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Lijie Zeng
From the Department of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China.
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Hui Liu
From the Department of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China.
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Liyan Li
From the Department of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China.
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Zhaoyun Liu
From the Department of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China.
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Rong Fu
From the Department of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China.
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    Figure 1

    - Differences in T-cells and their subsets between patients with PNH and healthy controls. A) In comparison to healthy controls, the proportion of total T-cells (CD3+) increased considerably. B) We found that patients with PNH had higher percentages of CD3+CD8+ and CD8+CD4+ cells, which is consistent with the T-cell results. CD4+/CD8+ ratio was decreased in patients with PNH. C) In both groups, in the proportion of CD3+CD4+ cells were the same. D-G) Positive correlations were found between the number of CD3+ cells in patients with PNH and LDH, indirect bilirubin levels, and Flear− cells in monocytes; on the other hand, negative correlations were seen with hemoglobin levels.

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    Figure 2

    - Differences in B-cells and their subsets between patients with PNH and healthy controls. A) Patients with PNH had a lower proportion of total B-cells. B) The proportion of naive B-cells were decreased. The percentage of CD21low B-cells, Class-unswitched memory B-cells and Class-switched memory B-cells increased significantly. C) The percentages of Marginal zone B-cells, Breg-cells and Transitional B-cell were not different between the 2 groups. D&E) The proportion of CD19+ cells is negatively correlated with LDH level and the ratio of Flear− cells in monocytes.

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    Figure 3

    - Differences in DC cells and their subsets between patients with PNH and healthy controls. A) When comparing patients to healthy controls, there was an increase in the proportion of total DC cells. B) The percentage of pDC/DC% was lower while mDC/DC% was higher than normal controls. There was also a marked decrease in the pDC/mDC and mDC1/mDC ratio. C) The ratio of mDC2/mDC and CD16+mDC/mDC did not have distinction between patients and controls. D) The proportion of mDC/DC cell was positively correlated with CD59− cells (II + III types) in red cells and Flear− cells in granulocytes and monocytes.

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    Figure 4

    - Differences in several cytokines and their subsets between patients with PNH and healthy controls. A) The plasma concentration of IL-6 increased and IL-17A are decreased in PNH, compared with healthy controls. B) Hemoglobin levels and IL-17A plasma concentration are correlated.

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    Table 1

    - Hematological and clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria.

    CharacteristicsPNH patients (n=25)Healthy controls (n=50)
    Age in years, median (range)48.5 (23-68)45 (20-68)
    Male/female, n (%)14/11 (56/44)27/23 (54/46)
    PNH clones, median (range)
    Flear- cells in granulocyte88.23 (59.73-98.55)NA
    Flear- cells in monocytes90.02 (50.06-99.52)
    CD59- cells (II+III types)43.83 (3.28-97.58)
    History of AA, n (%)5 (20.0)NA
    Current treatment, n (%)
    Supportive5 (20.0)NA
    Hormone16 (64.0)
    Cyclosporin A4 (16.0)
    Peripheral blood values, median (range)
    Hb (g/L)65.5 (39-126)133 (109-153)
    Platelets (x109/L)116 (7-242)210 (167-298)
    WBC (x109/L)3.72 (0.62-10.41)6.42 (5.88-10.02)
    Retic (%)7.615 (1.67-44.02)0.67 (0.45-1.55)
    LDH (U/L), median (range)1171 (276-4053)189 (102-225)
    IBIL (umol/L), median (range)18.5 (5.6-45.2)6.8 (1.6-11.3)
    Cr (μmol/L), median (range)54 (27-142)66 (44-103)
    D-Dimer (mg/L), median (range)928.5 (112-5217)NA
    History of thrombosisn, n (%)3 (12.0)NA

    Values are presented as numbers and precentages (%) or median (range). PNH: paroxysmal nocturnal hemoglobinuria, AA: aplastic anemia, Hb: hemoglobin, WBC: white blood cell, Retic: reticulocyte, LDH: lactate dehydrogenase, IBIL: Indirect bilirubin, Cr: creatinine, NA: not applicable.

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    The immunologic abnormalities in patients with paroxysmal nocturnal hemoglobinuria are associated with disease progression
    Guanrou Wang, Mengting Che, Lijie Zeng, Hui Liu, Liyan Li, Zhaoyun Liu, Rong Fu
    Saudi Medical Journal Apr 2024, 45 (4) 424-432; DOI: 10.15537/smj.2024.45.4.20231010

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    The immunologic abnormalities in patients with paroxysmal nocturnal hemoglobinuria are associated with disease progression
    Guanrou Wang, Mengting Che, Lijie Zeng, Hui Liu, Liyan Li, Zhaoyun Liu, Rong Fu
    Saudi Medical Journal Apr 2024, 45 (4) 424-432; DOI: 10.15537/smj.2024.45.4.20231010
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    Keywords

    • paroxysmal nocturnal hemoglobinuria
    • T-cells
    • B-cells
    • dendritic cells
    • cytokines

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