title: Abnormal CD4 + T helper (Th) 1 cells and activated memory B cells are associated with type III asymptomatic mixed cryoglobulinemia in HCV infection.
abstract: BACKGROUND
  Mixed cryoglobulinemia (MC) in hepatitis C virus (HCV) infection is associated with abnormal immune responses mediated by T cells and B cells, while the relationships of different subsets of CD4 + T helper (Th) cells, B cells and associated cytokines with type III asymptomatic MC in HCV infection are poorly understood.
  
  
  METHODS
  Fifty-four chronic hepatitis C (CHC) patients and 23 healthy controls (HCs) were enrolled in the study. Serum cryoglobulins were detected by cryoprecipitation. The types of cryoglobulin were determined by western blot. The phenotypes and frequencies of Th cell and B cell subsets were detected by flow cytometric analysis. The cytokines IFN-γ, IL-4, IL-17, IL-21, IL-22, and TGF-β were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Twenty-six CHC patients were detected with type III asymptomatic MC. The frequencies of Th2, Th17, follicular helper T (Tfh cells), Th22, and tissue-like B cells were significantly higher in CHC patients compared to HCs, while these cell subsets were not significantly different between CHC patients and HCV-related MC patients. The frequencies of Th1 and activated memory B cells increased in HCV-related MC patients compared to HCs, although the difference between the two cell subsets in CHC patients and HCs was not significant. The frequency of regulatory T cells (Treg cells) was higher in CHC patients than in HCV-related MC patients and HCs. Higher expressions of serum IFN-γ, IL-17, IL-21, and IL-22 were observed in CHC patients than in HCs, but the differences were not significantly different in CHC patients and HCV-related MC patients. The frequency of Th1 cells was associated with activated memory B cells in HCV-related MC patients, and the frequency of Th1 cells and activated memory B cells was closely related to HCV RNA in HCV-related MC patients.
  
  
  CONCLUSIONS
  The increased frequencies of Th17 cells, Tfh cells, Th22 cells, Treg cells, cytokines IL-17, IL-21, IL-22, and tissue-like B cells, were related to HCV infection but not type III asymptomatic MC. Higher frequencies of Th1 cells and activated memory B cells were associated with type III asymptomatic MC in HCV infection.
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, No.11 Xizhimen South Street, Beijing, 100044, China. kong.fanyun@163.com.|Department of Pathogenic biology and Laboratory of Infection and Immunology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu Province, China. kong.fanyun@163.com.
authors.forename: Fanyun
authors.initials: F
authors.lastname: Kong
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, No.11 Xizhimen South Street, Beijing, 100044, China. jiesuifanny@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, No.11 Xizhimen South Street, Beijing, 100044, China. xyfyfb_1@sina.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Feng
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, No.11 Xizhimen South Street, Beijing, 100044, China. zhhbao@163.com.
authors.forename: Henghui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, No.11 Xizhimen South Street, Beijing, 100044, China. rao.huiying@163.com.
authors.forename: Huiying
authors.initials: H
authors.lastname: Rao
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, No.11 Xizhimen South Street, Beijing, 100044, China. to_wjh@163.com.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, No.11 Xizhimen South Street, Beijing, 100044, China. olivercongxu@vip.sina.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Cong
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, No.11 Xizhimen South Street, Beijing, 100044, China. weilai@pkuph.edu.cn.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D003449:Cryoglobulinemia / Q000209:etiology*; D003450:Cryoglobulins / Q000032:analysis; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006526:Hepatitis C / Q000150:complications* / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D003450:Cryoglobulins; D016207:Cytokines