Immunodeficiency for Severe Epstein-Barr Virus Infection
Condition: Epstein-Barr Virus Infections; Immunodeficiency
MeSH terms: Infections; Communicable Diseases; Virus Diseases; Epstein-Barr Virus Infections; Immunologic Deficiency Syndromes
Study type: Observational

Summary: 
      The purpose of this study is to investigate the immune responses associated with Epstein-Barr
      virus infections, and to find out the possible immunodeficiency that may be linked to severe
      Epstein-Barr virus infections.
    

Detailed description: 
      Epstein-Barr virus (EBV) belongs to herpesviridae family, which infects more than 90% of the
      population. EBV infection is usually asymptomatic and establishes lifelong persistence in the
      host, although primary infection later than adolescence frequently results in infectious
      mononucleosis (IM). Rarely, individuals may develop a subgroup of EBV-associated life
      threatening complications (including liver dysfunction, haemophagocytosis and malignancy).

      Although EBV-infected B cells have the potential for proliferation, they are effectively
      removed by the EBV-specific cytotoxic T cells (CTL). In the immunocompetent hosts, natural
      killer (NK) cells and antigen-specific cluster designation 8 (CD8+) T-cells play an important
      role in inhibiting progression of primary EBV infection by granule-mediated cytotoxicity. The
      immune system is necessary to control the virus-induced transformation and the B-cell
      unlimited proliferation.

      Primary immunodeficiency are a heterogeneous group of hereditary diseases that are associated
      with compromised immune responses. There are a number of immunodeficiency resulting in
      inability of immune system to control EBV infection, for example X-linked Lymphoproliferative
      disease (XLP)/signaling lymphocyte activation molecule (SLAM)-associated protein (SAP)
      deficiency, X-linked inhibitor of apoptosis (XIAP) deficiency, cluster of differentiation
      antigen 27 (CD27) deficiency, interleukin-2-inducible T-cell kinase (ITK) deficiency, and so
      on. Whereas, some other clinical states associated with EBV-susceptibility remain largely
      unknown. Rare EBV-infected individuals without apparent immunodeficiency also present with
      persistent IM-like symptoms, hepatosplenomegaly, liver dysfunction, lymphadenopathy and
      haemophagocytic lymphohistiocytosis.

      Patients presenting with severe EBV infections should be focused on early identification of a
      possible primary immunodeficiency or a chronic active EBV infection clinical condition
      (CAEBV) and haemophagocytic lymphohistiocytosis(HLH). Immunological phenotyping of NK-, T-
      and B-cell differentiation, and functional assays including cytotoxic cell killing function
      and cytotoxic granule release, provide a useful identification for clinical conditions
      inability to control EBV infections. Genomic DNA is isolated from peripheral blood
      mononuclear cells and will be amplified to screen for possible immunodeficiency.

      The reasons for those patients inability to control the EBV infection are still unknown.
      However no effective treatment is currently available, those patients might benefit from
      early hematopoietic stem cell transplantation (HSCT). Through this study, we hope to identify
      the unknown immune immunodeficiency and pathophysiology of those EBV-associated conditions.
      The investigators propose to help make early diagnosis and develop effective therapies.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        We will evaluate immunodeficiency incidence in patients with severe EBV infection
      
Biospecimen description: 
      Heparinized peripheral blood is obtained from patients with severe EBV infections. Samples is
      performed after parents' information and consent.
    
Keywords: Epstein-Barr Virus Infections; Immunodeficiency; Screening; Immunologic Function