Transcript Introduction / Review of Literature: Sjogren`s syndrome is an

Hydroxychloroquine-linked lymphoma
development in a mouse model of Sjogren’s
Syndrome
Morgan Adams
Department of Biological Sciences,
York College of Pennsylvania
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Anticipated Results:
Proposed Methods:
Introduction / Review of Literature:
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Sjogren’s syndrome is an
autoimmune disease that targets
the lacrimal and salivary glands
(Dong et al. 2013).
The glands have an overaccumulation of lymphocytes that
prevent them from producing their
designated secretions, thus leading
to damage of those glands
(Deshmukh et al. 2008).
It is known that patients with this
disease have an increased risk of
developing lymphoma over their life
time (Dong et al. 2013).
Hydroxychloroquine is an
antimalarial drug that is now being
used to decrease the inflammation
associated with the disease (Ben-Zvi
et al. 2012).
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Obtain 20 mice from Jackson Laboratories.
Ten mice will be treated with Freund’s
incomplete adjuvant, an immunostimulant
that induces Sjogren’s-like symptoms.
Ten mice will be treated with a placebo not
to induce any symptoms.
Five mice from the immunostimulant group
will be treated with HCQ, 5 will not. The
same will be done for the nonimmunostimulant group.
Blood samples will be taken from salivary
glands, peripheral lymph nodes and
peripheral blood to see if lymphoma
develops.
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Mice treated with hydroxychloroquine
will develop lymphoma after constant
treatment over a 12 week process
Mice that were not treated with HCQ will
not develop cancer over this time.
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Figure 1. Anticipated amounts of lymphocytes in the different
treatment groups.
Control Group
(not treated with immunostimulant)
Experimental group
(treated with immunostimulant)
Treatment with
HCQ
Treatment with
placebo
Future Studies
The use of this mouse model could lead to the
understanding of the mechanism the drug takes
to affect patients with Sjogren’s syndrome.
12 weeks old
Hypothesis:
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The mice treated with Freund’s adjuvant will
develop Sjogren’s like symptoms.
The mice treated with HCQ will show higher
levels of lymphocytes in their blood smears.
The mice that were not treated with HCQ
should not have extremely high lymphocyte
levels.
If the development of lymphoma is only
associated with Sjogren’s the HCQ should not
increase the amount of lymphocytes.
Treatment with
HCQ
Treatment with
placebo
Literature Cited:
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Daily for 12 weeks
Histology
samples
taken
Histology
samples
taken
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Histology
samples
taken
Histology
samples
taken
Ben-Zvi, I., Kivity, S., Langevitz, P., and Shoenfeld, Y. 2012.
Hydroxychloroquine: from malaria to autoimmunity. 42(2): 145-153
Deshmukh, U.S., Ohyama, Y. Bagavant, H., Guo, X., Gaskin, F., and Fu,
M.S. 2008. Inflammatory stimuli accelerate Sjogren’s syndrome-like
disease in NZB/WF1 mice. Arthritis Rheum. 58(5) 1318-1323.
Dong, L., Chen, Yu., Masaki, Y., Okazaki, T., and Umehara, H. 2013.
Possible mechanisms of lymphoma development in Sjogren’s
syndrome. Current Immunology Reviews. (9): 13-22.
Acknowledgments:
I would like to thank Dr. Singleton for mentoring me through this
process.