Clinical trial NCT03374566: Immunodeficiency for Severe Epstein-Barr Virus Infection
Official title: Screening for Immunodeficiency Diseases in Patients With Severe Epstein-Barr Virus Infection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Epstein-Barr Virus Infections
Immunodeficiency
Keywords: Epstein-Barr Virus Infections
Immunodeficiency
Screening
Immunologic Function
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
First posted: 2017-12-15
Enrollment: 100
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We will evaluate immunodeficiency incidence in patients with severe EBV infection

Brief 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.

Eligibility criteria: Inclusion Criteria:

* 1. Age：birth to 18 years 2. Severe Epstein-Barr Virus infection

Exclusion Criteria:

* 1. Lack of parental consent

Primary outcomes:
measure: Immunodeficiency incidence in patients with severe EBV infection
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Children's Hospital of Fudan University
name: Jinqiao Sun, Ph.D.,M.D
role: PRINCIPAL_INVESTIGATOR
References:
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