Peripheral Blood Lymphocyte Subsets in Factor VIII Inhibitor-Positive Patients with Severe Hemophilia A: A Case-Control Study.

IF 2.3 4区 医学 Q2 HEMATOLOGY
Lu Zhao, Yiqun Zhang, Xinlei Guo, Zhi Li, Wenliang Lu, Zhijuan Pan, Yanru Guo, Jiajia Sun, Ying Zhang, Jinyu Hao, Zhiping Guo
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Abstract

Introduction and objectives: The present study aimed to investigate different peripheral lymphocyte subsets in patients with severe hemophilia A (HA) and factor VIII (FVIII) inhibitor production. For this, age-matched cases of 19 FVIII inhibitor-positive (IP), 21 FVIII inhibitor-negative (IN) and 45 healthy controls were selected for study.

Methods: Flow cytometry was used to analyze the peripheral lymphocyte subsets, including T, B, natural killer (NK) and NKT cells. The T cell subsets included CD3 + CD4-CD8- [double negative T (DNT)], CD3 + CD4 + CD8+ [double-positive T (DPT)], CD3 + CD4 + CD8- and CD3 + CD4-CD8+ T cells. Pairwise comparisons of absolute lymphocyte subset values were conducted among the three groups. The cut-off value for absolute lymphocyte counts was determined using receiver operating characteristic curve analysis.

Results: The results demonstrated that the absolute values of DPT cells in the IN and IP groups were significantly lower than those in the healthy control group (P = 0.007). The DNT values were also lower in severe HA patients with or without inhibitor than those in healthy subjects, but these differences were not statistically significant (P = 0.053). In addition, the absolute value of CD4+ Th cells in the IP group was lower than that in the healthy controls (P = 0.013). Although not statistically significant (P = 0.064), the absolute values of NKT cells were higher in the IN group compared with the IP group, and higher in the IP group compared with the healthy control group. There were no statistically significant differences in total T, B, CD8 + and NK cells among the IN, IP and healthy control groups. The cut-off value for absolute CD4+ Th cells in the IN group was < 598/µl.

Conclusion: The decrease in absolute values of CD4+ Th cells in severe HA patients may contribute to the establishment of infused FVIII immune tolerance. If the CD4+ Th value remains > 598/µl, clinicians should be vigilant for possible FVIII inhibitor production, especially on days prior to FVIII exposure.

因子 VIII 抑制剂阳性重度血友病 A 患者的外周血淋巴细胞亚群:一项病例对照研究。
导言和目的:本研究旨在调查严重A型血友病(HA)患者不同的外周淋巴细胞亚群以及因子VIII(FVIII)抑制剂的产生情况。为此,研究人员选择了年龄匹配的 19 例 FVIII 抑制剂阳性(IP)、21 例 FVIII 抑制剂阴性(IN)和 45 例健康对照者:采用流式细胞术分析外周淋巴细胞亚群,包括 T 细胞、B 细胞、自然杀伤细胞(NK)和 NKT 细胞。T 细胞亚群包括 CD3 + CD4-CD8- [双阴性 T(DNT)]、CD3 + CD4 + CD8+ [双阳性 T(DPT)]、CD3 + CD4 + CD8- 和 CD3 + CD4-CD8+ T 细胞。对三组淋巴细胞绝对亚群值进行配对比较。采用接收者操作特征曲线分析法确定了淋巴细胞绝对计数的临界值:结果表明,IN 组和 IP 组的 DPT 细胞绝对值明显低于健康对照组(P = 0.007)。使用或不使用抑制剂的重症 HA 患者的 DNT 值也低于健康人,但差异无统计学意义(P = 0.053)。此外,IP 组 CD4+ Th 细胞的绝对值低于健康对照组(P = 0.013)。虽然没有统计学意义(P = 0.064),但 IN 组的 NKT 细胞绝对值高于 IP 组,IP 组的 NKT 细胞绝对值也高于健康对照组。IN 组、IP 组和健康对照组的 T、B、CD8 + 和 NK 细胞总数差异无统计学意义。IN 组 CD4+ Th 细胞绝对值的临界值为结论:重症 HA 患者 CD4+ Th 细胞绝对值的下降可能有助于输注 FVIII 免疫耐受的建立。如果 CD4+ Th 值仍大于 598/µl,临床医生应警惕可能产生的 FVIII 抑制剂,尤其是在暴露于 FVIII 的前几天。
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来源期刊
CiteScore
4.40
自引率
3.40%
发文量
150
审稿时长
2 months
期刊介绍: CATH is a peer-reviewed bi-monthly journal that addresses the practical clinical and laboratory issues involved in managing bleeding and clotting disorders, especially those related to thrombosis, hemostasis, and vascular disorders. CATH covers clinical trials, studies on etiology, pathophysiology, diagnosis and treatment of thrombohemorrhagic disorders.
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