Protein Studies of the Epstein-Barr Virus in Ethnically Diverse Populations
| Status: | Completed |
|---|---|
| Conditions: | Infectious Disease, Infectious Disease |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | October 2003 |
| End Date: | April 2008 |
Comprehensive Epitope Mapping of the Epstein-Barr Virus Latent Membrane Protein-2 in Ethnically Diverse Populations
This study will evaluate the ability of people of different ethnic backgrounds to develop
immune responses against the Epstein-Barr virus (EBV). A common virus, EBV is present in 90
percent of healthy people and usually does not cause problems. Most people are infected in
childhood, have no symptoms, and are unaware of their infection. People infected as
adolescents or adults may develop infectious mononucleosis, which usually resolves
completely. However, in immune suppressed people, like those who have had a transplant, EBV
can cause fatal cancers. It can also cause certain cancers such as Burkitt's lymphoma,
Hodgkin's lymphoma, and nasopharyngeal carcinoma in people who are not immune suppressed.
Nasopharyngeal carcinoma is 100 times more common in people of Asian origin (particularly
southern Chinese) compared with Caucasians. This difference may be the result of genetic,
rather than environmental, factors. This study will examine whether the same proteins
produced by EBV in the cancer cells react differently in people of different ethnic
background in a way that could explain the differences in predisposition for this disease.
Healthy normal volunteers 18 years of age and older of Caucasian or Chinese ancestry may be
eligible for this study. Candidates of Chinese ancestry must be born in China (including
Taiwan, Hong Kong, and Singapore, or be first generation offspring of parents born in these
places).
Participants will have a blood sample drawn and will undergo lymphapheresis - a procedure
for collecting large numbers of white blood cells called lymphocytes. The blood sample is
tested for blood counts and HLA type, a genetic marker of the immune system. HLA molecules
help determine the way the body's immune cells respond to virus. HLA typing is similar to
blood typing. Usually done to match stem cell or organ transplants, HLA testing may also be
used to try to identify factors associated with an increased risk of certain diseases or
conditions. HLA type is strongly associated with ethnic background.
For lymphapheresis, blood is collected through a needle in an arm vein, similar to donating
blood. The blood flows from the vein through a catheter (plastic tube) into a machine that
separates it into its components by centrifugation (spinning). The white cells are removed
and the rest of the blood (red cells, plasma and platelets) is returned to the body through
a needle in the other arm. The procedure takes 2 to 3 hours. The collected white cells are
used for research for this study, including the ability to react to EBV proteins, and are
then destroyed.
immune responses against the Epstein-Barr virus (EBV). A common virus, EBV is present in 90
percent of healthy people and usually does not cause problems. Most people are infected in
childhood, have no symptoms, and are unaware of their infection. People infected as
adolescents or adults may develop infectious mononucleosis, which usually resolves
completely. However, in immune suppressed people, like those who have had a transplant, EBV
can cause fatal cancers. It can also cause certain cancers such as Burkitt's lymphoma,
Hodgkin's lymphoma, and nasopharyngeal carcinoma in people who are not immune suppressed.
Nasopharyngeal carcinoma is 100 times more common in people of Asian origin (particularly
southern Chinese) compared with Caucasians. This difference may be the result of genetic,
rather than environmental, factors. This study will examine whether the same proteins
produced by EBV in the cancer cells react differently in people of different ethnic
background in a way that could explain the differences in predisposition for this disease.
Healthy normal volunteers 18 years of age and older of Caucasian or Chinese ancestry may be
eligible for this study. Candidates of Chinese ancestry must be born in China (including
Taiwan, Hong Kong, and Singapore, or be first generation offspring of parents born in these
places).
Participants will have a blood sample drawn and will undergo lymphapheresis - a procedure
for collecting large numbers of white blood cells called lymphocytes. The blood sample is
tested for blood counts and HLA type, a genetic marker of the immune system. HLA molecules
help determine the way the body's immune cells respond to virus. HLA typing is similar to
blood typing. Usually done to match stem cell or organ transplants, HLA testing may also be
used to try to identify factors associated with an increased risk of certain diseases or
conditions. HLA type is strongly associated with ethnic background.
For lymphapheresis, blood is collected through a needle in an arm vein, similar to donating
blood. The blood flows from the vein through a catheter (plastic tube) into a machine that
separates it into its components by centrifugation (spinning). The white cells are removed
and the rest of the blood (red cells, plasma and platelets) is returned to the body through
a needle in the other arm. The procedure takes 2 to 3 hours. The collected white cells are
used for research for this study, including the ability to react to EBV proteins, and are
then destroyed.
Epstein Barr virus (EBV) can induce in immune compromised patients fatal lymphoproliferative
lesions that regress upon reversion of immune suppression or adoptive transfer of
EBV-specific CD8+ T cells. EBV can also induce neoplastic lesions in immune competent hosts
including Burkitt's lymphoma, Hodgkin's disease and nasopharyngeal cancer (NPC).
EBV-specific CD8+ T cell responses can occur in patients with these cancers that are
qualitatively similar but quantitatively diminished compared to EBV-primed normal
individuals. Although these cancers share several features, they are characterized by
divergent patterns of expression of EBV proteins. In particular, NPC expresses
preferentially the latent membrane protein (LMP) 2 with or without expression of LMP 1 and
intermediate expression of the Epstein-Barr nuclear antigen. Thus, there is interest to
develop LMP 2-directed immunizations for patients with NPC with the hope that enhancement of
the insufficient natural immunity may lead to tumor regression. Since, the incidence of NPC
is tightly associated with ethnic background (principally Southern Chinese) and Human
Leukocyte Antigen (HLA) phenotype, diverse populations may display distinct reactivity
patterns toward EBV epitopes that may in turn be responsible for their respective
predisposition to acquire NPC. Although, several LMP 2 epitopes have been described, to our
knowledge, no systematic mapping across diverse ethnicity complemented with high-resolution
HLA typing has ever been done. We, therefore, propose to map immune dominant epitopes of LMP
2 in EBV primed normal individuals of Caucasian or Asian (Chinese) ethnicity by measuring
interferon (IFN)-gamma transcript levels in circulating lymphocytes exposed to a library of
overlapping nonamer peptides encompassing the full sequence of LMP 2. High resolution,
sequence-based HLA typing will complement the study.
lesions that regress upon reversion of immune suppression or adoptive transfer of
EBV-specific CD8+ T cells. EBV can also induce neoplastic lesions in immune competent hosts
including Burkitt's lymphoma, Hodgkin's disease and nasopharyngeal cancer (NPC).
EBV-specific CD8+ T cell responses can occur in patients with these cancers that are
qualitatively similar but quantitatively diminished compared to EBV-primed normal
individuals. Although these cancers share several features, they are characterized by
divergent patterns of expression of EBV proteins. In particular, NPC expresses
preferentially the latent membrane protein (LMP) 2 with or without expression of LMP 1 and
intermediate expression of the Epstein-Barr nuclear antigen. Thus, there is interest to
develop LMP 2-directed immunizations for patients with NPC with the hope that enhancement of
the insufficient natural immunity may lead to tumor regression. Since, the incidence of NPC
is tightly associated with ethnic background (principally Southern Chinese) and Human
Leukocyte Antigen (HLA) phenotype, diverse populations may display distinct reactivity
patterns toward EBV epitopes that may in turn be responsible for their respective
predisposition to acquire NPC. Although, several LMP 2 epitopes have been described, to our
knowledge, no systematic mapping across diverse ethnicity complemented with high-resolution
HLA typing has ever been done. We, therefore, propose to map immune dominant epitopes of LMP
2 in EBV primed normal individuals of Caucasian or Asian (Chinese) ethnicity by measuring
interferon (IFN)-gamma transcript levels in circulating lymphocytes exposed to a library of
overlapping nonamer peptides encompassing the full sequence of LMP 2. High resolution,
sequence-based HLA typing will complement the study.
- INCLUSION CRITERIA:
Normal volunteers, age greater than or equal to 18 years of Caucasian or Chinese ancestry
will be eligible for the study. Chinese ancestry will be defined as being born in China
(including Taiwan, Hong Kong and Singapore) or being first generation offspring of parents
born in China (including Taiwan, Hong Kong and Singapore).
ECOG performance status of 0 or 1.
Individuals must weigh at least 110 pounds.
Potential participants must pass the criteria for blood donors established by the American
Association of Blood Banks according to the routine screening performed within the
Department of Transfusion Medicine.
Potential participants should pass a brief physical exam to exclude potential cardiac
problems.
WBC 3000/mm(3) or greater.
Platelet count 90,000 mm(3) or greater.
Negative pregnancy test
Ante-cubital veins compatible with the apheresis process. Apheresis center nurses will
assess the ante-cubital veins of all subjects prior to enrollment. If their veins are
judged to be too small to support the intravenous catheter required for the procedure,
they will be excluded. If at the time of each apheresis procedure the nurses are unable to
obtain adequate ante-cubital vein access, the subject will be excluded.
Evidence of previous exposure to EBV infection will not represent inclusion criteria.
EXCLUSION CRITERIA:
Potential participants will be excluded:
Who are undergoing or have undergone in the past 3 weeks any form of systemic therapy that
may affect immune function.
Who have active systemic infections, autoimmune disease or any known immunodeficiency
disease.
Who require systemic steroid therapy.
Who are pregnant.
Who are positive for hepatitis B (s)AG or HIV antibody (because of possible immune effects
of these conditions). HIV testing will be performed prior to enrollment.
Who have any form of active primary or secondary immune deficiency.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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