Immunology Graduate Group
Arnold I. Levinson, M.D.
Allergy and Immunology,
Department of Medicine
University of Pennsylvania Medical Center
Phone: (215) 898-4592
Email: frog@mail.med.upenn.edu
Education:
B.S., University of Maryland
M.D., University of Maryland School of Medicine
Post Doctoral Fellow, University of Pennsylvania
Research Interest
Cellular and molecular basis of human autoimmune disease
Research Summary
Role of the thymus in the pathogenesis of myasthenia gravis
The lab is interested in analyzing the expression of acetylcholine receptors in the thymus in an effort to determine how intrathymic expression of this autoantigen may predispose to development of the prototypic autoimmune disease, myasthenia gravis (MG). Our studies focus on the cellular localization of these receptors at the protein and mRNA levels, as well as their quantitation, and molecular regulation. We study human tissue obtained at the time of thymectomy. In addition, we have established a mouse model to determine if an antecedent inflammatory response in the thymus alters lymphocyte trafficking back to this organ and leads to a breach of tolerance to locally expressed self-antigens, including acetylcholine receptor.
Impact of a B cell superantigen on the immune response
We are studying the impact of a novel type of antigen, a B cell superantigen, on the immune system. Unlike a conventional antigen, a B cell superantigen has the potential to react with a large numbers of B cells or large amounts of soluble immunoglobulin. We found that the interaction of a prototypic B cell superantigen with the immune system leads to activation of the classical complement cascade in vitro and immune complex mediated tissue injury in vivo. Studies are underway to delineate the cellular and molecular basis for this immunopathologic response and to determine if such pro-inflammatory features are characteristic of other B cell superantigens.
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Semiquantitative RT-PCR: Representative Southern blot depicting expression of acetylcholine receptor alpha subunit (AchRa) P3A- and P3A+ isoforms in thymus specimens from three Control subjects and seven MG patients. A comparison of the intensity of the AChRa template bands to the standard strongly suggests that both isoforms are expressed in greater amounts in MG thymus than in Control thymus. |
Publications
Zheng Y., Wheatley L.M., Liu T, and Levinson A.I.: Acetylcholine receptor alpha subunit mRNA expression in human thymus: Augmented expression in myasthenia gravis and upregulation by interferon-g. Clin. Immunol.91:170,1999.
Levinson A.I., Zheng Y., Gaulton G., Song D. C., Moore J., and Pletcher H.: Intrathymic Expression of Neuromuscular Acetylcholine Receptors and the Immunpathogenesis of Myasthenia Gravis. Immunol. Res., 27:399-408, 2003.
Levinson A.I., Zheng Y., Gaulton G., Moore J., and Pletcher H., Song D. C., and Wheatley L.M.: A New Model Linking Intrathymic Acetylcholine Receptor Expression and the Pathogenesis of Myasthenia Gravis. In Myasthenia gravis and related disorders. Ann. N.Y. Acad. Sci. 998:257-265, 2003.
Kozlowski L.M., Li W., Goldschmidt M., and Levinson A.I: In vivo inflammation induced by a prototypic B cell superantigen. Elicitation of an Arthus reaction by Staphylococcal protein A requires its immunoglobulin VH binding site. J. Immunol.160:5246, 1998.