Enhanced B‐cell differentiation driven by advanced cirrhosis resulting in hyperglobulinemia

Abstract

Enhanced TLR9-induced differentiation into antibody secreting cell may explain peripheral reductions of circulating CD27 memory B cells as well as increased serum Ig levels in cirrhosis.

Reduced Energy Metabolism Impairs T Cell-Dependent B Cell Responses in Patients With Advanced HBV-Related Cirrhosis

“…B cells in HBV-related advanced cirrhosis had a lower percentage of memory B cells, a higher ratio of plasmablasts and an increased percentage of naïve B cells, which was in accordance with the findings of other studies ( 10 , 11 ). Memory B cells were chronically activated in advanced cirrhosis, as memory B cells in advanced cirrhosis were more easily activated by TLR9 plus elevated PAMP levels in cirrhotic conditions ( 10 , 11 ). Activated memory B cells differentiate into short-lived antibody-secreting plasmablasts, increasing the percentage of plasmablasts and the consumption of memory B cells ( 23 , 24 ).…”

“…A decrease in the CD27 + memory subgroup among cirrhotic B cells may contribute to this effect ( 10 ). Regarding B cell functional changes after stimulation, the conclusions were contradictory: one result showed that activation of peripheral B cells in cirrhosis was attenuated after CD40/TLR9 stimulation, manifesting as reductions in CD70 expression and IgG production ( 10 ), and the other result demonstrated that cirrhotic B cells were prone to differentiate into plasma cells and produce increased amounts of immunoglobulins ( 11 ). Although the damaged humoral response in cirrhosis has been confirmed, the mechanism and B cell response after activation, especially the T cell-dependent B cell response, remain to be further explored, as T cell help plays a pivotal role in humoral immunity.…”

Hyperactive Follicular Helper T Cells Contribute to Dysregulated Humoral Immunity in Patients With Liver Cirrhosis

“…The contribution of hyperactive Tfh cells to plasma cell differentiation may lead to the increased levels of non-specific antibodies and autoimmune antibodies during cirrhosis. It is reported that cirrhotic patients manifested hyper-immunoglobnemia (9) and had more anti-microbial antibodies than control subjects (27). Therefore, the enhanced systemic inflammation and Tfh cell immunity in cirrhotic patients may break the barrier tolerance and facilitate the induction of anti-microbial antibodies, which consequently affect the normal symbiosis of gut flora and lead to the increased microbial translocation.…”

“…LC profoundly depletes the circulating CD27 + memory B cells (7, 8). Accompanying this, hyper-globulinemia and elevated IgG and IgA levels were observed in advancing cirrhosis, irrespective of the underlying etiology (9). LC also causes T cell lymphopenia and disrupts T cell compartments.…”

Inversed albumin-to-globulin ratio and underlying liver disease severity as a prognostic factor for survival in hepatocellular carcinoma patients undergoing transarterial chemoembolization

“…Globulins consist of several proinflammatory proteins (14), including C-reactive protein, α2-macroglobulin, fibrinogen, prothrombin, and serum amyloid A (34). Since immunoglobulins in humans are mainly metabolized by the liver, the ability to clear immunoglobulins in patients with severe hepatic dysfunction may be reduced, resulting in hyperglobulinemia (35,36).Tumor-related inflammation stimulates the production of various cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor (37), which can act on the liver and induce the synthesis of positive acute-phase reactants (34). This might explain the increased serum globulin levels observed in this study.…”