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Is aberrant CD8+ T cell activation by hypertension associated with cardiac injury in severe cases of COVID-19?

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Cellular & Molecular Immunology 2020年第6期17卷 675-676页

作者： Chao Zhang fu-sheng wang Jean-Sébastien Silvestre Fernando Arenzana-Seisdedos Hong Tang Treatment and Research Center for Infectious Diseases The Fifth Medical Center of PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijingChina Inserm UMRS 970 Paris Centre de Recherche Cardiovasculaire(PARCC)75737 Paris cedex 15CedexFrance CAS Key Laboratory of Molecular Virology and Immunology COVID-19 Response TeamInstitut Pasteur of ShanghaiChinese Academy of SciencesShanghaiChina

COVID-19 global pandemic,caused by severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2),1 has swept 185 countries and regions with more than 2,824,728 confirmed cases,and 197,667 death as on April 25,2020 according the Coronavirus Resource Center at Johns Hopkins University.Accumulating data suggest that hypertension,diabetes,and cardiovascular diseases are the most frequent comorbidities in COVID-19 patients,and case mortality rates tended to be high in these individuals.

关键词： hypertension cases Hopkins

Complement 5a receptor-mediated neutrophil dysfunction is associated with a poor outcome in sepsis

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Cellular & Molecular Immunology 2016年第1期13卷 103-109页

作者： Ruonan Xu Fang Lin Chunmei Bao Huihuang Huang Chengcheng Ji Siyu wang Lei Jin Lijian Sun Ke Li Zheng Zhang fu-sheng wang Research Centre for Biological Therapy The Institute of Translational Hepatology Beijing 302 Hospital Beijing China The Institute of Intensive Care Unit Beijing 302 Hospital Beijing China Centre of Clinical Laboratory Medicine Beijing 302 Hospital Beijing China

Complement 5a （C5a） has been implicated in the pathogenesis of sepsis by inducing the functional impairment of neutrophils; however, the utility of C5a receptors （C5aRs; C5aR and C5L2） as biomarkers for the management of sepsis is uncertain. This study investigated the dynamic expression of C5aR and C5L2 on neutrophits and their effects on neutrophil function. We found that sepsis patients displayed low expression levels of C5aR and C5L2 on neutrophils compared to healthy and systemic inflammatory response syndrome （SIRS） subjects, and this expression pattern was correlated with disease severity. Additionally, the expression levels of C5aR and C5L2 were associated with the survival of sepsis patients. In vitro, the addition of C5a significantly reduced C5aR and C5L2 expression levels and IL-8 production in neutrophils from sepsis patients. Those findings suggest that the reduced expression of C5aRs was associated with the functional impairment of neutrophils and a poor prognosis for sepsis patients. Overall, these findings may help establish C5aRs expression levels as early markers to predict the severity of sepsis.

关键词： complement 5a complement 5a receptor neutrophil prognosis sepsis

Frequency and Absolute Number of FoxP3^+ Regulatory T Cells Correlate with Disease Progression of Chronic HIV-1 Infection

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Virologica Sinica 2007年第6期22卷 501-508页

作者： Jun-liang fu fu-biao KANG Yan-mei JIAO Shao-jun XING Bao-yun fu Chun-bao ZHOU Xi-cheng wang Hao WU fu-sheng wang Research Center of Biological Therapy Beijing Institute of Infectious Diseases Beijing 302 Hospital 100 Xi Si Huan Middle Road Beijing 100039 China Postgraduate Team Military Postgraduate Medical CollegeBeijing 100853 China Department of Infectious Diseases Beijing You-An Hospital Affiliated to Capital University of Medical Science Beijing 100054 China

CD4+CD25+ Regulatory T cells (Treg) have been found to down-regulate immune activation in HIV-1 infection. However,whether the depletion of Treg benefits to the disease status of HIV infection remains undefined. To address this issue,we enumerated the Treg absolute counts and frequency in 75 antiviral-nave HIV-1-infected individuals in this study. It was found that HIV-infected patients displayed a significant decline in Treg absolute counts but a significant increase in Treg frequency. In addition,with disease progression indicated by CD4 T-cell absolute counts,circulating Treg frequency gradually increased; while Treg absolute counts were gradually decreased,suggesting that the alteration of Treg number closely correlated with disease progression in HIV infection. functional analysis further showed that Treg efficiently inhibit both CD4 and CD8 T cell proliferation in vitro. Thus,our findings indicates that Treg actively participate in pathogenesis of chronic HIV infection,influencing the disease progression.

关键词： T细胞艾滋病艾滋病病毒侵染疾病进展频率数量病毒复制

IDI: Building a Bridge of Communication Between China and Other Nations in the Field of Infectious Diseases

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Infectious Diseases & Immunity 2021年第1期1卷 1-2页

作者： fu-sheng wang Department of Infectious Diseases Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijing 100039China

A century ago,an imported plague epidemic broke out in Northeast China.At that time,Mr.Liande Wu was the person responsible for handling the outbreak situation.China promptly took measures such as quarantine,isolation,and diagnosis and treatment and successfully eliminated the severe infectious disease that shocked the world in 4months.At present,the COVID-19 epidemic broke out in Wuhan,China.Under the leadership of the Communist Party of China and Chinese authorities,China has adopted comprehensive measures such as early detection and diagnosis,treatment,and isolation to control the epidemic within 3months,embodying China’s considerable anti-epidemic spirit:life is supreme,the whole country is of one mind,regardless of life and death,respecting science,and destiny together.The prompt actions taken,efficiency,and experience that China has shown indicate that it has gradually been at the forefront of the global fight against infectious diseases.However,with the exception of China and a few countries,COVID-19 remains to threaten human health worldwide.

关键词： prompt measures isolation

Reversal of B-cell hyperactivation and functional impairment is associated with HBsAg seroconversion in chronic hepatitis B patients

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Cellular & Molecular Immunology 2015年第3期12卷 309-316页

作者： Xiangsheng Xu Qinghua Shang Xinyue Chen Weimin Nie Zhengsheng Zou Ang Huang Ming Meng Lei Jin Ruonan Xu Ji-Yuan Zhang Junliang fu Lifeng wang Zirong Tang Yunbo Xie Xiaoming Yang Zheng Zhang fu-sheng wang Beijing Institute of Radiation Medicine Beijing China Research Center for Biological Therapy The Institute of Translational Hepatology Beijing 302Hospital Beijing 100039 China Department of Infectious Diseases 88th Hospital of PLA Taian Shandong China Department of Infectious Diseases Beijing You'an Hospital Affiliated to Capital Medical University Beijing China Department of Infectious Diseases Beijing 302 Hospital Beijing China Department of Non-infectious Diseases Beijing 302 Hospital Beijing China Institute of Basic Medicine Hebei University Baoding China Xiangsheng Xu and Qinghua Shang have contributed equally to this work.

B cells play an important role in the clearance of hepatitis B virus （HBV） and protection against reinfection. However, the functional characteristics of these cells that are associated with the outcome of chronic HBV infection remain unknown. We comprehensively investigated the frequency, phenotype, and function of peripheral B-cell subsets from CHB patients in different phases： immune tolerance （IT）, immune activation （IA）, immune clearance （IC）, responders with HBsAg seroconversion （resolved patients, RP）, and healthy controls （HC）. IA patients displayed lower percentages of peripheral blood memory B cells compared with the other groups. Overall polyclonal activation of B cells, indicated by higher levels of activation markers and secretion of IgG and IgM, was observed in IA patients. This B-cell hyperactivation could be induced by increased IFN-a and soluble CD40 ligands in IA patients. Notably, the expression of the co-stimulator molecule CD80 and serum HBsAb and the frequency of HBsAg-specific B cells were significantly decreased in IT, IA, and IC patients compared with HC subjects. More importantly, the B-cell hyperactivation, co-stimulatory molecule downregulation and HBsAg-specific B-cell impairment were reversed in RP patients. The reversal of B-cell hyperactivation and functional impairment is associated with HBsAg seroconversion in chronic hepatitis B patients.

关键词： Reversal hyperactivation functional

Guidelines for the Prevention and Treatment of Chronic Hepatitis B(Version 2022)

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Infectious Diseases & Immunity 2023年第4期3卷 145-162页

作者： Hong You fu-sheng wang Taisheng Li Xiaoyuan Xu Yameng Sun Yuemin Nan Guiqiang wang Jinlin Hou Zhongping Duan Lai Wei Jidong Jia Hui Zhuang Chinese Society of Hepatology,Chinese Medical Association Chinese Society of Infectious Diseases,Chinese Medical Association Beijing Friendship Hospital Capital Medical UniversityBeijing 100050China The Fifth Medical Center of PLA General Hospital Beijing 100039China Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Peking University First Hospital Beijing 100034China Third Hospital of Hebei Medical University Shijiazhuang 050051China Nanfang Hospital Southern Medical UniversityGuangzhou 516006China Beijing You-An Hospital Capital Medical UniversityBeijing 100069China Tsinghua Changgung Hospital Tsinghua UniversityBeijing 102218China Peking University Health Science Center Beijing 100191China 不详

To facilitate the achieving of the goal of“eliminating viral hepatitis as a major public health threat by 2030”set by theWorld Health Organization,the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases(both are branches of the ChineseMedical Association)organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China(version 2022).With the support of available evidence,this revision of the guidelines focuses on active prevention,large-scale testing,and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B–related disease burden.

关键词： Hepatitis B,chronic Treatment Prevention Guideline

Improved survival ratios correlate with myeloid dendritic cell restoration in acute-on-chronic liver failure patients receiving methylprednisolone therapy

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Cellular & Molecular Immunology 2012年第5期9卷 417-422页

作者： Juan Zhao Ji-Yuan Zhang Hong-Wei Yu Yu-Lan He Jing-Jing Zhao Juan Li Yue-Ke Zhu Qin-Wei Yao Jin-Huan wang Hai-Xia Liu Shu-Yun Shi Zheng-sheng Zou Xiang-sheng Xu Chun-Bao Zhou fu-sheng wang Qing-Hua Meng Department of Hepatology Beijing You An HospitalCapital Medical UniversityBeijingChina Research Center for Biological Therapy The Institute of Translational HepatologyBeijing 302 HospitalBeijingChina Department of Infectious Disease Beijing 302 HospitalBeijingChina juan Zhao and Ji-Yuan Zhang contributed equally to this work.

Acute-on-chronic liver failure （ACLF） is a severe life-threatening complication. Liver transplantation is the only available therapeutic option; however, several limitations have restricted its use in patients. The use of corticosteroids as an optional therapy for ACLF has received a great deal of interest. The rationale behind its use is the possible role of the immune system in initiating and perpetuating hepatic damage. In order to assess the relationship between myeloid dendritic cells （mDCs） and the efficacy of methylprednisolone （MP） treatment for hepatitis B virus （H BV）-associated ACLF patients, we recruited 30 HBV-associated ACLF patients who had received MP treatment at lO-day intervals; 26 patients received conservative medical （CM） management as a control. The functionality of DC subsets was lower in these ACLF patients compared with healthy subjects. In addition, compared with survivors, dead/transplanted patients had lower functional mDC in both groups. furthermore, a decreased numbers of mDC at baseline was associated with high mortality of ACLF patients. Importantly, MP treatment resulted in a significant decrease in 28-day mortality, and all MP patients exhibited an initial rapid decrease in circulating mDC numbers within 10 days of MP treatment. Subsequently, MP survivors displayed a continuous increase in mDC numbers accompanied by a decrease in total bilirubin levels by more than 30%. However, MP dead/ transplanted patients lacked these sequential responses compared with survivors. This evidence suggests strongly that the higher mDC numbers at baseline and the recovery of mDC number at the end of treatment may represent a prognostic marker for favorable response to corticosteroid treatment in ACLF patients.

关键词： acute-on-chronic liver failure methylprednisolone myeloid dendritic cells plasmacytoid dendritic cells

Investigation of immune escape-associated mutations of hepatitis B virus in patients harboring hepatitis B virus drug-resistance mutations

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World Journal of Gastroenterology 2020年第35期26卷 5314-5327页

作者： Bi-Xia Huang Yan Liu Zhen-Ping Fan Lan-Lan Si Rong-Juan Chen Jun wang Dan Luo fu-sheng wang Dong-Ping Xu Xin-Guang Liu Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics/Institute of Biochemistry&Molecular Biology Guangdong Medical UniversityDongguan 523808Guangdong ProvinceChina Institute of Infectious Diseases the Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Infectious Diseases the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina

It is unclear whether immune escape-associated mutations in the major hydrophilic region of hepatitis B virus surface antigen(HBsAg)are associated with nucleoside/nucleotide analog resistance.AIM To evaluate the association between immune escape-associated mutations and nucleoside/nucleotide analog resistance mutations.METHODS In total,19440 patients with chronic hepatitis B virus infection,who underwent resistance testing at the Fifth Medical Center of Chinese PLA General Hospital between July 2007 and December 2017,were enrolled.As determined by sequence analysis,6982 patients harbored a virus with resistance mutations and 12458 harbored a virus lacking resistance mutations.Phenotypic analyses were performed to evaluate HBsAg production,replication capacity,and drug-induced viral inhibition of patient-derived drug-resistant mutants with or without the coexistence of sA159V.RESULTS The rate of immune escape-associated mutation was significantly higher in 9 of the 39 analyzed mutation sites in patients with resistance mutations than in patients without resistance mutations.In particular,these mutations were sQ101H/K/R,sS114A/L/T,sT118A/K/M/R/S/V,sP120A/L/Q/S/T,sT/I126A/N/P/S,sM133I/L/T,sC137W/Y,sG145A/R,and sA159G/V.Among these,sA159V was detected in 1.95%(136/6982)of patients with resistance mutations and 1.08%(134/12,458)of patients lacking resistance mutations(P<0.05).The coexistence of sA159V with lamivudine(LAM)and entecavir(ETV)-resistance mutations in the same viral genome was identified during follow-up in some patients with drug resistance.HBsAg production was significantly lower and the replication capacity was significantly higher,without a significant difference in LAM/ETV susceptibility,in sA159V-containing LAM/ETV-resistant mutants than in their sA159V-lacking counterparts.CONCLUSION In summary,we observed a close link between the increase in certain immune escape-associated mutations and the development of resistance mutations.sA159V might increase the fitness of LAM/ETV-resistant mutants under env

关键词： Hepatitis B virus Immune escape-associated mutation Drug-resistance mutation Nucleoside/nucleotide analogs Hepatitis B surface antigen Major hydrophilic region

What Should Be Done to Re-evaluate Cessation of Nucleos(t)ide Analog Therapy for Chronic Hepatitis B Infection?

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Infectious Diseases & Immunity 2021年第2期1卷 93-102页

作者： Yongqian Cheng Yingjie Ji Huijuan Duan Yuanyuan Li George Lau fu-sheng wang The Fifth Medical Center of Chinese PLA General Hospital(Beijing 302 Hospital) BeijingChina Humanity and Health Clinical Trial Center Humanity and Health Medical GroupHong Kong SARChina

Anti-viral therapy with nucleos(t)ide analogs(NUCs)for chronic hepatitis B(CHB)is generally considered to be a long-term treatment.Relevant guidelines issued by Asian Pacific Association for the Study of the Liver,European Association for the Study of the Liver,and American Association for the Study of Liver Diseases have recently proposed requirements and standards for cessation of NUCs,but it remains unclear which proportion of CHB patients on long-term or prolonged treatment of NUCs will relapse after NUCs cessation.Recently,paradoxical increase in loss of hepatitis B surface antigen(HBsAg)with or without the development of anti-hepatitis B surface antibody has been observed in NUCs’treated CHB patients with cessation of therapy.Hence,it is of great clinical relevance to identify CHB who might have been over-treated with NUCs and might even benefit HBsAg loss or seroconversion with cessation of therapy.To address these issues,our review comprehensively analyzed the data from recent clinical trials in which the antiviral efficacy in the long-term or prolonged treatment of NUCs and/or interferon-a for CHB patients were evaluated.furthermore,the relevant problems and deficiencies existing in the study design of previous clinical studies were also described.To solve the unmet issues in the field,a prospective study with a large-enough sample size would be required to understand the related virologic and immunological markers that can accurately predict the outcome and prognosis of the CHB patients who stop the NUCs treatment.With the rapid advancement of antiviral drug development for CHB patients,the future ideal regimens should include multiple targets for antiviral drug therapy combined with efficient immune-modulatory therapy,which will help more CHB patients to obtain functional cure with NUCs cessation.

关键词： Hepatitis B,chronic Cessation of therapy Nucleoside analogs