HCV-related immunocytoma and type II mixed cryoglobulinemia-associated autoantigens

Maria Paola Simula, Laura Caggiari, Annunziata Gloghini, Valli De Re

Research output: Chapter in Book/Report/Conference proceedingConference contribution

7 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) is a hepatotropic virus causing hepatocellular damage and chronic liver inflammation that progressively can lead to cirrhosis and hepatocellular carcinoma (HCC). HCV is also lymphotropic, as demonstrated by its capacity to replicate in lymphocytes, by the recurrent detection of organ- and non-organ-specific autoantibodies in HCV-infected patients, and by the strong association found between HCV infection and type II mixed cryoglobulinemic syndrome (MC-II). Moreover, accumulating data ascribe an etiopathogenetic role in the development of B cell non-Hodgkin's lymphomas (NHL) to HCV. All these findings account for the profound effect of HCV infection in the host's immune system. The unique virus-host interactions that culminate in the generation and sustained production of autoantibodies and cryoglobulins have not been delineated. It appears that chronic antigenic stimulation could cause the emergence of specific B cell clones that produce cryoglobulins; moreover, B cell activation and/or deregulation could originate as a result of HCV binding to CD81 tetraspanin or as a consequence of its ability to replicate in B cells. In a previous study we demonstrated that, in MC-II HCV-positive patients, cryoprecipitated monoclonal IgMs, and B cell receptors (BCR) of overexpanded B cell clones share the same combinatory region. Moreover, these IgMs were reactive against both the Fc region of human IgG and the HCV-NS3 antigen. NS3 and Fc epitopes have been identified by epitope excision approach. One of the identified NS3 epitopes has been used to immunize a mouse and the monoclonal antibody obtained showed the same cross-reactivity as patients' IgMs. The characterization of antigenic specificity of this antibody may be useful to identify antigens that can stimulate B cell proliferation in HCV-infected individuals.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Pages121-130
Number of pages10
Volume1110
DOIs
Publication statusPublished - Sep 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1110
ISSN (Print)00778923
ISSN (Electronic)17496632

Fingerprint

Cryoglobulinemia
Autoantigens
Viruses
Hepacivirus
B-Lymphocytes
Epitopes
Cryoglobulins
Clone cells
Cells
Virus Diseases
Autoantibodies
Clone Cells
Antigens
Virus Attachment
B-Cell Lymphoma
Deregulation
Lymphocytes
Immune system
Non-Hodgkin's Lymphoma
Cell proliferation

Keywords

  • Autoantibodies
  • B cell proliferation
  • Hepatitis C virus
  • Hepatocarcinoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Simula, M. P., Caggiari, L., Gloghini, A., & De Re, V. (2007). HCV-related immunocytoma and type II mixed cryoglobulinemia-associated autoantigens. In Annals of the New York Academy of Sciences (Vol. 1110, pp. 121-130). (Annals of the New York Academy of Sciences; Vol. 1110). https://doi.org/10.1196/annals.1423.014

HCV-related immunocytoma and type II mixed cryoglobulinemia-associated autoantigens. / Simula, Maria Paola; Caggiari, Laura; Gloghini, Annunziata; De Re, Valli.

Annals of the New York Academy of Sciences. Vol. 1110 2007. p. 121-130 (Annals of the New York Academy of Sciences; Vol. 1110).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Simula, MP, Caggiari, L, Gloghini, A & De Re, V 2007, HCV-related immunocytoma and type II mixed cryoglobulinemia-associated autoantigens. in Annals of the New York Academy of Sciences. vol. 1110, Annals of the New York Academy of Sciences, vol. 1110, pp. 121-130. https://doi.org/10.1196/annals.1423.014
Simula MP, Caggiari L, Gloghini A, De Re V. HCV-related immunocytoma and type II mixed cryoglobulinemia-associated autoantigens. In Annals of the New York Academy of Sciences. Vol. 1110. 2007. p. 121-130. (Annals of the New York Academy of Sciences). https://doi.org/10.1196/annals.1423.014
Simula, Maria Paola ; Caggiari, Laura ; Gloghini, Annunziata ; De Re, Valli. / HCV-related immunocytoma and type II mixed cryoglobulinemia-associated autoantigens. Annals of the New York Academy of Sciences. Vol. 1110 2007. pp. 121-130 (Annals of the New York Academy of Sciences).
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AB - Hepatitis C virus (HCV) is a hepatotropic virus causing hepatocellular damage and chronic liver inflammation that progressively can lead to cirrhosis and hepatocellular carcinoma (HCC). HCV is also lymphotropic, as demonstrated by its capacity to replicate in lymphocytes, by the recurrent detection of organ- and non-organ-specific autoantibodies in HCV-infected patients, and by the strong association found between HCV infection and type II mixed cryoglobulinemic syndrome (MC-II). Moreover, accumulating data ascribe an etiopathogenetic role in the development of B cell non-Hodgkin's lymphomas (NHL) to HCV. All these findings account for the profound effect of HCV infection in the host's immune system. The unique virus-host interactions that culminate in the generation and sustained production of autoantibodies and cryoglobulins have not been delineated. It appears that chronic antigenic stimulation could cause the emergence of specific B cell clones that produce cryoglobulins; moreover, B cell activation and/or deregulation could originate as a result of HCV binding to CD81 tetraspanin or as a consequence of its ability to replicate in B cells. In a previous study we demonstrated that, in MC-II HCV-positive patients, cryoprecipitated monoclonal IgMs, and B cell receptors (BCR) of overexpanded B cell clones share the same combinatory region. Moreover, these IgMs were reactive against both the Fc region of human IgG and the HCV-NS3 antigen. NS3 and Fc epitopes have been identified by epitope excision approach. One of the identified NS3 epitopes has been used to immunize a mouse and the monoclonal antibody obtained showed the same cross-reactivity as patients' IgMs. The characterization of antigenic specificity of this antibody may be useful to identify antigens that can stimulate B cell proliferation in HCV-infected individuals.

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