Abstract
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 (both p < 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 and p < 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.
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This study was supported by JSPS KAKENHI (Grant Numbers 16K08973 and 19K08478); Kitasato University Research Grant for Young Researchers (grant number 2013, 2014, 2015); and Kitasato University School of Allied Health Sciences (Grants-in-Aid for Research Project, No. 2017–1014, 2018–1026, and 2019–1015).
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Satoh T., Takiguchi H., and Uojima H. designed the study. Satoh T., Takiguchi H., Tanaka C., and Yokoyama F. performed experiments and analyzed the data. Kubo M. and Kuwana M. offered technical support. Horie R. and Kuwana M. offered material support. Uojima H., Wada N., Miyazaki K., Hidaka H., Kusano C., and Horie R. collected clinical data. Satoh T. drafted the manuscript. All authors discussed and approved the final manuscript.
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Satoh, T., Takiguchi, H., Uojima, H. et al. B cell-activating factor is involved in thrombocytopenia in patients with liver cirrhosis. Ann Hematol 101, 2433–2444 (2022). https://doi.org/10.1007/s00277-022-04973-x
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DOI: https://doi.org/10.1007/s00277-022-04973-x