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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Hydroxychloroquine-linked lymphoma development in a mouse model of Sjogren’s Syndrome Morgan Adams Department of Biological Sciences, York College of Pennsylvania Introduction / Review of Literature: Sjogren’s syndrome is an autoimmune disease that targets the lacrimal and salivary glands (Dong et al. 2013). The glands have an over- accumulation 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). Hypothesis: 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. Proposed Methods: 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 non- immunostimulant group. Blood samples will be taken from salivary glands, peripheral lymph nodes and peripheral blood to see if lymphoma develops. Anticipated Results: 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. Literature Cited: Ben-Zvi, I., Kivity, S., Langevitz, P., and Shoenfeld, Y Hydroxychloroquine: from malaria to autoimmunity. 42(2): Deshmukh, U.S., Ohyama, Y. Bagavant, H., Guo, X., Gaskin, F., and Fu, M.S Inflammatory stimuli accelerate Sjogren’s syndrome-like disease in NZB/WF1 mice. Arthritis Rheum. 58(5) Dong, L., Chen, Yu., Masaki, Y., Okazaki, T., and Umehara, H Possible mechanisms of lymphoma development in Sjogren’s syndrome. Current Immunology Reviews. (9): Acknowledgments: I would like to thank Dr. Singleton for mentoring me through this process. Experimental group (treated with immunostimulant) Control Group (not treated with immunostimulant) Treatment with HCQ Treatment with placebo Treatment with HCQ Treatment with placebo Histology samples taken 12 weeks old Daily for 12 weeks 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. Figure 1. Anticipated amounts of lymphocytes in the different treatment groups.