Chinese scientists have revealed a new mechanism for chronic hepatitis B and a new strategy for immunotherapy

Researchers from the Institute of Life Histology/National Protein Science Center (Beijing) of the Military Academy of Sciences found that abnormal immune function of antiviral body fluids is an important cause of chronic infection of hepatitis B, and activation and restoration of body fluid immune function can significantly promote the removal of HBV. This discovery not only puts forward a new understanding of the pathogenesis of chronic hepatitis B, but also points out a new direction for the development of chronic hepatitis B treatment drugs. The findings were published online in the world's top international journals
. The authors of this study are Tang Li Researcher and He Fuchu, and the first author is Dr. Wang Xiaowen, Ph.D. students Dong Qingyang and Li Wei. The study was also supported by a team of academicians from Wang Fusheng of the PLA 302 Hospital.
hepatitis B is a caused by HBV infection caused by the world disease, but also one of the most burdened diseases in our society. Nearly 100 million of the world's approximately 350 million HBV carriers are in China, and more than 700,000 people die each year from chronic hepatitis B complications, including cirrhosis and liver cancer, which account for half Chinese of the disease. Although the widespread use of preventive hepatitis B vaccine has led to a significant decrease in the rate of new infections of HBV, there is still a lack of effective treatment for patients with chronic hepatitis B infection.
virus infection, the body can produce a specific antiviral immune response to remove the virus. However, the virus also shows weakness, evolved an efficient latent infection strategy to escape the body's immune attack. The study found that the antiviral immunity of patients with chronic hepatitis B is inhibited, failed or toned. Therefore, the treatment of chronic hepatitis B, increasingly widely recognized trend is a two-pronged approach: both antiviral, but also to mobilize immunization. The antiviral immune response mainly includes cellular immunity and body fluid immunity. In the late 1970s, researchers began developing a preventive hepatitis B vaccine that produces protective antibodies by stimulating the body's immune response. However, cd8, one of the main representatives of cellular immunity,
T cells, is the key effect cell for HBV removal. Therefore, there have been systematic studies on the immunosuppression pathology of CD8
T cells for chronic hepatitis B, and at the same time, breaking the immunosuppressive environment and inducing antiviral CD8
T cell immune response have gradually brought new dawn to the treatment of chronic hepatitis B. However, as one of the main representatives of body fluid immunity B cells, people's understanding of its contribution in the fight against hepatitis B infection, but also stay at the level of preventive hepatitis B vaccine, that is, B-cell-mediated body fluid immune production neutral antibodies, before infection can prevent HBV infection, and there is nothing that can be done for patients with hepatitis B infection. The reason is that there has been little research and little knowledge of the body fluid immune response mechanism of chronic hepatitis B and its related intervention strategies for a long time.
Tang Li / Hefuchu academician team first established a mouse model that can simulate clinical acute and chronic HBV infection, and on this basis found that B cell-mediated body fluid immunity, especially surface antibody response, the contribution to HBV removal is much higher than previously recognized. In the acute HBV mouse model of CD20 antibody treatment (removal of B cells in the body), B cell differentiation defect or folytic auxiliary T cell (Tfh cell) differentiation defect that assists B cells in producing antibodies, the serum and HBV removal in the liver were significantly impaired; On the basis of fully realizing that B-cell-mediated body fluid immunity has an important contribution to HBV removal, they further traced the characteristics of body fluid immunological abnormalities of chronic hepatitis B and their back causes, and found that abnormal Treg cells appeared in chronic hepatitis B mice, which inhibited Tfh cell response, resulting in B-cell surface antibody response defects, which led to virus removal obstruction. More importantly, their findings in mouse models showed that they were also validated in clinical exoclinical blood samples in patients with hepatitis B. These studies have found that Tfh-B cell-mediated body fluid immunity plays a key role in HBV removal, and suggest that breaking down specific body fluid immunosuppression environments and activating body fluid immune response may lead to a new breakthrough in the treatment of chronic hepatitis B.
, as expected, they further found that there are feasible and effective intervention strategies for chronic hepatitis B immune response abnormalities! Previous studies have suggested that CTLA-4 is a key molecule in the inhibitory function of Treg cells. Inspired by this, they injected chronic HBV mice with CTLA-4 closed antibodies, which were found to break the immunosuppressive environment created by Treg cells, restore the function of Tfh-B cells, secrete surface antibodies and significantly accelerate virus removal. They then validated the key findings using clinical samples from patients with hepatitis B. As the industry is known, CTLA-4-specific antibody ipilimumab has been approved for immunotherapy of tumors as early as 2011. For the first time, the team proposed a "new use of old drugs" strategy and demonstrated that CTLA-4 antibodies can target Treg cells, restore the surface antibody response of hepatitis B, and treat chronic infections of hepatitis B. They are conducting more in-depth and extensive research to this end.
the study was jointly funded by the National Natural Science Foundation of China, the 863 Program and the 973 Program. (Source: Science.com)