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Rods & Rings: Targets of Emerging Autoantibodies

HeLa cells with rods and rings

HeLa cells labeled to visualize rods and rings (rabbit polyclonal anti-IMPDH2, green), microtubules (mouse monoclonal anti-tubulin, red) and nuclei (DAPI, blue)

Historically, there have been few examples of human autoantibodies used in elucidating novel subcellular macromolecular complexes and structures. Dr. Chan and colleagues have identified novel human autoantibodies recognizing conserved rods and rings (RR) in the cytoplasm of many cell types examined to date. The data has been validated using newly acquired cells from the American Tissue Culture Collection to rule out artifacts from continued in vitro culturing. Candidate RR proteins have been identified and will allow for a number of interesting studies to investigate the biology of these structures at the cellular level. Continuing identification of key RR protein components will better define the function of these structures.

From the clinical perspective, preliminary data show that a majority of patients with the RR antibody are positive for hepatitis C virus. The overall goal of the proposed studies is to elucidate the structure and function of RR and gain insight into patients positive for anti-RR autoantibodies. The proposed studies will span across molecular and cell biology, virology, and autoimmunity.

Current Project Members

  • S. John Calise
  • Joyce D. Yin
  • Thuy Nguyen
  • Dania Saleem

Collaborators

  • Minoru Satoh, M.D., Ph.D., Dept. of Clinical Nursing, University of Occupational and Environmental Health, Kitakyushu, Japan
  • Chen Liu, M.D., Ph.D., Dept. of Pathology, UF College of Medicine, Gainesville, FL
  • Daniel L. Purich, Ph.D., Dept. of Biochemistry and Molecular Biology, UF College of Medicine, Gainesville, FL

Key Publications

2014

Calise, S.J., Carcamo, W.C., Ceribelli, A., Dominguez, Y., Satoh, M., and Chan, E.K. Antibodies to rods and rings. In Autoantibodies (Shoenfeld, Y., Gershwin, M.E., Meroni, P.L., Eds.), pp. xxx-xxx. Elsevier Science, in press.

Calise, S.J., Carcamo, W.C., Krueger, C., Yin, J.D., Purich, D.L., and Chan, E.K. Glutamine deprivation initiates reversible assembly of mammalian rods and rings. Cell Mol Life Sci. [Epub ahead of print]

Carcamo, W.C., Calise, S.J., von Mühlen, C.A., Satoh, M., and Chan, E.K. Molecular cell biology and immunobiology of mammalian rod/ring structures. Int Rev Cell Mol Biol., 308:35-74.

2013

Carcamo, W.C., Ceribelli, A., Calise, S.J., Krueger, C., Liu, C., Daves, M., Villalta, D., Bizzaro, N., Satoh, M., and Chan, E.K. Differential reactivity to IMPDH2 by anti-rods/rings autoantibodies and unresponsiveness to pegylated interferon-alpha/ribavirin therapy in US and Italian HCV patients. J Clin Immunol. 33:420-6.

2012

Keppeke, G.D., Nunes, E., Ferraz, M.L., Silva, E.A., Granato, C., Chan, E.K., and Andrade, L.E. Longitudinal Study of a Human Drug-Induced Model of Autoantibody to Cytoplasmic Rods/Rings following HCV Therapy with Ribavirin and Interferon-α. PLoS One 7:e45392.

Covini, G., Carcamo, W.C., Bredi, E., von Mühlen, C.A., Colombo, M., and Chan, E.K. Cytoplasmic rods and rings autoantibodies developed during pegylated interferon and ribavirin therapy in patients with chronic hepatitis C. Antiviral Therapy 10.3851/IMP1993.

2011

Carcamo, W.C., Satoh, M., Kasahara, H., Terada, N., Hamazaki, T., Chan, J.Y., Yao, B., Tamayo, S., Covini, G., von Mühlen, C.A., and Chan, E.K. Induction of cytoplasmic rods and rings structures by inhibition of the CTP and GTP synthetic pathway in mammalian cells. PLoS One 6:e29690.