Download Pilot Study of the Effects of Thymus Protein on Elevated Epstein

Pilot Study of the Effects of Thymus Protein on
Elevated Epstein-Barr Virus Titers
by Neil H. Riordan, PA-C, BS1;James A. Jackson, PhD, MT (ASCP),CLS, BCLD2;and Hugh D. Riordan, MD3
Project RECNAC
Bio-Communications Research Institute
3 100 N. Hillside Ave. Wichita, Kansas 67219
Financud Support Pcnfied pmteln A from calf thymus cell culture (BloPm Thym~cProte~nATM).was a plfl fmm LOngewty Sc~enca,New York, New York
lymphoproliferative d i ~ o r d e r s and
,~
neurological disorder^.^ In addition to
primoinfection and reactivation, a
chronic-active EBV infection has been
described."
EBV infection occurs more
frequently in immunocompromised
hosts?1° and has been reported to be
immunopathologic in presumably
immunocompetent h ~ s t s . ' A
~ cytOtoxic
.~~
T-lymphocyte (CTL) response i s
responsible for resolution of EBV
infections.l3
Purified protein A from calf thymus
cell culture (BioProThymic Protein ATM)
is a patented, over-the-counter
supplement which contains a
polypeptide that has shown the ability
Background
to stimulate mature T lymphocytes and
enhance mammalian immune response
Epstein-Barr virus (EBV) infection
1 is extremely common, approaching to infectious agents a n d to
malignancies.14 This polypeptide was
100% by the age of 10 in some parts of
the world. EBV is thought to be spread
first studied a t UCLA in 1979. Since that
via the respiratory route, and is the
time, a bovine thymus cell line which
produces t h e protein h a s been
causative a g e n t of infectious
rnononucleosi~.~
established.
The
protein
is
chromatographically purified from a
After acute infection, EBV has been
I shown to establish a latency state within medium used to culture the cell line. It
is now commercially available in a base
B lymphocytes, salivary gland
of maltodextrin, a n d is t a k e n
epithelium, a n d oropharyngeal
epithelial cells.2 Like other herpes
sublingually (4 mcg/dose).
viruses, EBV can reactivate.
Quantitation of IgG antibodies to
Primoinfection and reactivation of EBV
EBV early antigen (EBV EA) is
have been associated with several
commonly used to detect recent or
chronic-active infection. Elevated serum
disease states, including chronic fatigue
syndrome (CFS), Burkitt's l y m p h ~ m a , ~ viral capsid (EBV VCA) antibodies
indicate previous infection and can
I nasopharyngeal carcinoma,' aplastic
anemia,' Hodgkin's disease, several
remain elevated for life.
1
Abstract
S i x p a t i e n t s with chronically
e l e v a t e d Epstein-Barr virus early
a n t i g e n a n t i b o d y t i t e r s w.ere
t r e a t e d f o r 60 d a y s with purified
P r o t e i n A f r o m calf t h y m u s cell
c u l t u r e (BPTPA). T h e r e w a s a
statistically significant reduction of
antibody titers after treatment. T h e
t h y m i c protein was well tolerated
a n d i n c r e a s e d energy was reported
b y m o s t of the participants. These
resulta suggest t h a t BPTPA may be
useful in the treatment of patients
with persistently elevated EpsteinB a r r virus e a r l y antigen antibody
titers.
1
'
1
Objective
The objective of this study was to
determine what effect BPTPA, a T
lymphocyte stimulant, had on
chronically elevated EBV EA titers.
Methode
Seven patients meeting the criterion
of having persistent (>6 months) EA
titers of greater than or equal to 1:80
(Negative <1:20) were recruited to
participate in the study for 60 days.
Participation was entirely voluntary,
and informed consent was received from
all participants. The study protocol was
approved by our Institutional Review
Board and was carried out with the
ethical standards s e t forth in the
Helsinki Declaration of 1975.
Participants were provided with 4
mcg. packets of BioPro Protein& which
were taken sublingually,three times per
day, for a period of 60 days. At the end
of the study period, EBV EA and EBV
VCA levels were re-tested.
Participants were also requested to
complete a symptom questionnaire
before a n d after t h e study. The
questionnaire contained 86 current
symptom questions which were ranked
by the participants on a scale of 1-7
(lkno symptom, 7=severe symptom).
The pre- and post-treatment scores were
compared using the student T-test.
-Determinations of EBV EA ( 1 s ) and
EBV VCA (IgG) were performed by
Laboratory Corporation of America,
Wichita, Kansas. EBV EA (Negative:
1
78
TOWNSEND LElTEA for DOCTORS L PATIENTS
- F E ~ A U A R Y ~ M A R C1998
H
a
-.
13
'C]
5
-
2
p
I
<1:20) was quantified using indirect
fluorescent antibody, and EBV VCA
(Negative: <20 arbitrary units) was
determined
using
enzyme
immunoassay. The pre- and posttreatment scores for both assays were
compared using the student T-test.
Reeults
Of the seven patients enrolled, six
completed the study. One patient
discontinued use after 7 days after
experiencing flu-like symptoms which
resolved within three days of
discontinuation. No adverse side effects
were reported by t h e other six
participants. Four participants
completed both before and after
symptom questionnaires. Compliance
was good, with greater than 90% of dosea
taken. Table 1 shows the ages, sexes,
and diagnoses of the six participants.
T h e results of t h e study a r e
summarized in Table 2. After treatment
the EBV EA levels of four of the six
participants were reduced. The
reduction waa s&nXcaat(pe.03). There
was no reduction of the EBV VCA levels
after treatment.
The overall trend of the symptom
profiles was toward a reduction in
symptoms. Of the four before and after
profiles completed, two showed
1 significant (p=.04) reduction i n
symptoms after treatment (Table 3).
1
-
In poet-study i n t e ~ e w sall
, of the 5
participants with a diagnosis of CFS
reported increased energy and a
decrease in houm slept after the 60 day
treatment.
Also of note was that elevated liver
enzymes (ALT, AST, and GGT), and
cholesterol in patient number 3, who
had a concomitant diagnosis of hepatitis
C, and leukopenia in patient number 4,
were all normalized by the end of the
study.
Dhxssion
Although this was a non-blinded
pilot study, the fact that a significant
reduction of EBV EX titers occurred in
a group of patiente who had persistently
elevated titers suggests that BPTPA
may play a role in modulation of chronicactive EBV infection.
References
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lo.
Conclusion
The role of BPTPA in the
management of fatigue and chronicactive EBV infection should be studied
further.
11.
12.
Correspondence:
Neil H. Riordan, PA-C ,
Manager, Project RECNAC
Bi&mmunications Research Institute
3100 N. Hillside Ave.
Wichita, Kansas 67219 USA
316-682-3100
Fax 316-682-5054
13.
14.
:
.. .
-
4
1:320
1:SO
1:320
5 .
6
t-test
pC03 significant
1. Manager, Project RECNAC.
BioGommunications Reaearch
Institute. 3100 N. Hillside Ave..
Wichita. Kansas 67219
2. Professor, Wichita State
University, Department of
Medical Technology, Box 43,
Wichita, Kansas, 67260-0043.
3. Director, Project RECNAC,
Bio-Communications Research
Institute, 3100 N. Hillside Ave.,
Wichita. Kansas 67219
1:80
1:80
1:80
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