Immunodeficiency for Severe Epstein-Barr Virus Infection

NCT ID: NCT03374566

Last Updated: 2023-02-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-12-01

Study Completion Date

2023-02-01

Brief Summary

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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

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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.

Conditions

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Epstein-Barr Virus Infections Immunodeficiency

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Screened patients

Immunodeficiency screening: Heparinized peripheral blood is obtained from patients with severe EBV infections for immunological function assays and genetic analysis, when current screening is performed after parents' information and consent.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* 1\. Lack of parental consent
Minimum Eligible Age

1 Day

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Children's Hospital of Fudan University

OTHER

Sponsor Role lead

Responsible Party

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Jinqiao Sun

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jinqiao Sun, Ph.D.,M.D

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Fudan University

Locations

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Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, China

Site Status

Countries

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China

References

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Worth AJ, Houldcroft CJ, Booth C. Severe Epstein-Barr virus infection in primary immunodeficiency and the normal host. Br J Haematol. 2016 Nov;175(4):559-576. doi: 10.1111/bjh.14339. Epub 2016 Oct 17.

Reference Type BACKGROUND
PMID: 27748521 (View on PubMed)

Shabani M, Nichols KE, Rezaei N. Primary immunodeficiencies associated with EBV-Induced lymphoproliferative disorders. Crit Rev Oncol Hematol. 2016 Dec;108:109-127. doi: 10.1016/j.critrevonc.2016.10.014. Epub 2016 Nov 2.

Reference Type BACKGROUND
PMID: 27931829 (View on PubMed)

Palendira U, Rickinson AB. Primary immunodeficiencies and the control of Epstein-Barr virus infection. Ann N Y Acad Sci. 2015 Nov;1356:22-44. doi: 10.1111/nyas.12937. Epub 2015 Sep 28.

Reference Type BACKGROUND
PMID: 26415106 (View on PubMed)

Taylor GS, Long HM, Brooks JM, Rickinson AB, Hislop AD. The immunology of Epstein-Barr virus-induced disease. Annu Rev Immunol. 2015;33:787-821. doi: 10.1146/annurev-immunol-032414-112326. Epub 2015 Feb 11.

Reference Type BACKGROUND
PMID: 25706097 (View on PubMed)

Fujiwara S, Kimura H, Imadome K, Arai A, Kodama E, Morio T, Shimizu N, Wakiguchi H. Current research on chronic active Epstein-Barr virus infection in Japan. Pediatr Int. 2014 Apr;56(2):159-66. doi: 10.1111/ped.12314.

Reference Type BACKGROUND
PMID: 24528553 (View on PubMed)

Eligio P, Delia R, Valeria G. EBV Chronic Infections. Mediterr J Hematol Infect Dis. 2010 Aug 10;2(1):e2010022. doi: 10.4084/MJHID.2010.022.

Reference Type BACKGROUND
PMID: 21415952 (View on PubMed)

Other Identifiers

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EBV

Identifier Type: -

Identifier Source: org_study_id

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