Introduction of direct-acting antiviral agents alters frequencies of anti-GPIIb/IIIa antibody-producing B cells in chronic hepatitis C patients with thrombocytopenia

Introduction of direct-acting antiviral agents alters frequencies of anti-GPIIb/IIIa antibody-producing B cells in chronic hepatitis C patients with thrombocytopenia
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DOI:
10.1080/09537104.2022.2161498
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发表时间:
2023-12-31
期刊:
影响因子:
3.3
通讯作者:
Horie,Ryouichi
Horie,Ryouichi
中科院分区:
医学3区
文献类型:
--
作者:
Satoh,Takashi;Uojima,Haruki;Horie,Ryouichi

文献摘要

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慢性丙型肝炎(CHC)血小板减少症的发病机制可能与自身免疫有关;然而,自身抗体的动态和其他自身免疫机制仍不清楚。在这项研究中,我们检查了在CHC与直接作用抗病毒药物(DAA)治疗后,抗糖蛋白(GP)II B/IIIa抗体产生B细胞的频率和血浆B细胞活化因子(BAFF)、增殖诱导配体(APRIL)和白细胞介素(IL)-21水平的变化。我们招募了28例CHC患者,他们接受了8-12周的DAA治疗,随后血清丙型肝炎病毒RNA检测呈阴性。招募了30名健康对照进行比较。与DAA治疗前(基线)相比,治疗结束时(EOT)伴有血小板减少的CHC患者血小板计数显著增加(p= 0.016),抗GPIIb/IIIa抗体产生B细胞的频率显著降低(p= 0.002)。然而,在没有血小板减少的CHC患者中没有观察到这些变化。伴有血小板减少症的CHC患者的血浆BAFF水平从基线至EOT显著降低(p= .002)。在这些患者中,产生抗GPIIb/IIIa抗体的B细胞与血浆BAFF水平呈正相关(r= 0.669,p = 0.039)。这些结果表明,DAA治疗抑制血小板的自身免疫反应,改善血小板减少症。
The pathogenesis of thrombocytopenia in chronic hepatitis C (CHC) conceivably involves autoimmunity; however, the dynamics of autoantibodies and other autoimmune mechanisms remain unclear. In this study, we examined the changes in the frequency of anti-glycoprotein (GP) IIb/IIIa antibody-producing B cells and the levels of plasma B-cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), and interleukin (IL)-21 following treatment of CHC with direct-acting antiviral agents (DAA). We recruited 28 patients with CHC who underwent treatment with DAA for 8–12 weeks and subsequently tested negative for serum hepatitis C virus RNA. Thirty healthy controls were recruited for comparison. Platelet counts increased significantly (p= .016), and the frequency of anti-GPIIb/IIIa antibody-producing B cells decreased significantly (p= .002) in CHC patients with thrombocytopenia at the end of treatment (EOT) than before DAA treatment (baseline). However, these changes were not observed in CHC patients without thrombocytopenia. Plasma BAFF levels in CHC patients with thrombocytopenia significantly decreased from baseline to EOT (p= .002). Anti-GPIIb/IIIa antibody-producing B cells were positively correlated with plasma BAFF levels in these patients (r= 0.669,p= .039). These results suggest that DAA treatment suppresses the autoimmune response against platelets and improves thrombocytopenia.