B cell-activating factor is involved in thrombocytopenia in patients with liver cirrhosis
B cell-activating factor is involved in thrombocytopenia in patients with liver cirrhosis
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DOI：
10.1007/s00277-022-04973-x
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发表时间：
2022-09
影响因子：
3.5
通讯作者：
T. Satoh;Hayato Takiguchi;H. Uojima;M. Kubo;Chisato Tanaka;Fumiko Yokoyama;Naohisa Wada;K. Miyazaki;H. Hidaka;Chika Kusano;M. Kuwana;R. Horie
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文献类型：
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作者：
T. Satoh;Hayato Takiguchi;H. Uojima;M. Kubo;Chisato Tanaka;Fumiko Yokoyama;Naohisa Wada;K. Miyazaki;H. Hidaka;Chika Kusano;M. Kuwana;R. Horie
肝硬化（LC）涉及产生抗糖蛋白（GP）II B/IIIa抗体的B细胞，在原发性免疫性血小板减少症（ITP）中发现。自身免疫在LC血小板减少症病理学中的作用进行了研究，其中包括25例伴有血小板减少症的LC患者，18例ITP患者和30例健康对照。使用酶联免疫斑点试验定量抗GPIIb/IIIa抗体产生B细胞。采用酶联免疫吸附试验测定血小板相关和血浆抗GPIIb/IIIa抗体、血浆B细胞活化因子（BAFF）和增殖诱导配体（APRIL）水平。流式细胞术检测LC患者外周血B细胞亚群和调节性T细胞（TCLs），发现LC患者外周血产生抗GPIIb/IIIa抗体的B细胞数量显著高于ITP患者和健康对照组（P均< 0.001）。LC患者的血小板相关抗GPIIb/IIIa抗体显著高于ITP患者和健康对照组（分别为p= 0.002，p < 0.001）。LC患者的BAFF水平显著高于ITP患者和健康对照组（分别为p= 0.001和p < 0.001），LC患者的APRIL水平显著高于健康对照组（p< 0.001）。LC患者中产生抗GPIIb/IIIa抗体的B细胞和血小板相关抗GPIIb/IIIa抗体与BAFF水平呈正相关。LC患者的幼稚B细胞和浆母细胞比健康对照组多（分别为p= 0.005，p = 0.03）;浆母细胞与BAFF水平呈正相关。LC患者与ITP患者和健康对照组的TcR水平相似。因此，在伴有血小板减少症的LC患者中过多的BAFF产生可能与自身免疫性B细胞应答相关，诱导抗GPIIb/IIIa抗体产生。
Liver cirrhosis (LC) involves B cells that produce anti-glycoprotein (GP) IIb/IIIa antibodies, found in primary immune thrombocytopenia (ITP). The role of autoimmunity in the pathology of thrombocytopenia in LC was investigated using 25 LC patients with thrombocytopenia, 18 ITP patients, and 30 healthy controls. Anti-GPIIb/IIIa antibody-producing B cells were quantified using enzyme-linked immunospot assay. Platelet-associated and plasma anti-GPIIb/IIIa antibody, plasma B cell-activating factor (BAFF), and a proliferation-inducing ligand (APRIL) levels were measured using enzyme-linked immunosorbent assay. B cell subset fractions and regulatory T cells (Tregs) were quantified using flow cytometry.The number of anti-GPIIb/IIIa antibody-producing B cells was significantly higher in LC patients than in ITP patients and healthy controls (bothp< 0.001). Platelet-associated anti-GPIIb/IIIa antibodies were significantly higher in LC patients than in ITP patients and healthy controls (p= 0.002,p< 0.001, respectively). BAFF levels were significantly higher in LC patients than in ITP patients and healthy controls (p= 0.001 andp< 0.001, respectively), and APRIL levels were significantly higher in LC patients than in healthy controls (p< 0.001). Anti-GPIIb/IIIa antibody-producing B cells and platelet-associated anti-GPIIb/IIIa antibodies were positively correlated with BAFF levels in LC patients. LC patients had more naïve B cells and plasmablasts than healthy controls (p= 0.005,p= 0.03, respectively); plasmablasts were positively correlated with BAFF levels. LC patients had similar Tregs levels as ITP patients and healthy controls. Therefore, excessive BAFF production in LC patients with thrombocytopenia is likely associated with autoimmune B cell response, inducing anti-GPIIb/IIIa antibody production.