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Autoantibodies

IC61000 5-panel

A 4-color fluorescence image by Shangli Lian

Dr. Chan’s laboratory has a long history of the identification and characterization of specific autoimmune target antigens in different systemic rheumatic diseases. By understanding the biology of autoantigens in health and disease states, the functional and pathogenic potentials of autoantibodies may be finally appreciated. His early work focused on the study of human autoantibodies and autoantigens in systemic lupus erythematosus (SLE) and Sjögren’s syndrome, including the characterization of SS-B/La and the initial identification and cloning of the Ro52/TRIM21 autoantigen. His laboratory has been highly successful in using unique autoimmune antibodies as probes to identify and clone a number of interesting macromolecules:

  • the ribosomal RNA transcription factor NOR90/hUBF, localized to the nucleolar organizer region (NOR) on mitotic chromosomes
  • p80-coilin, the primary marker for the Cajal body, a coiled-coil-rich protein family of Golgi autoantigens known as golgins
  • GW182, a marker protein for cytoplasmic foci GW Bodies, also known as mammalian processing bodies

Current Project Members

  • S. John Calise

Collaborators

  • Minoru Satoh, M.D., Ph.D., Dept. of Clinical Nursing, University of Occupational and Environmental Health, Kitakyushu, Japan

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., Meroni, P.L., Gershwin, M.E., Eds.), pp. 161-168. Elsevier Science, Third Edition.

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.

Ceribelli, A., Satoh, M., and Chan, E.K. A new immunoprecipitation-real time quantitative PCR assay for anti-Th/To and anti-U3RNP antibody detection in systemic sclerosis. Arthritis Res Ther. 14:R128.

Ceribelli, A., Fredi, M., Taraborelli, M., Cavazzana, I., Franceschini, F., Quinzanini, M., Tincani, A., Ross, S.J., Chan, J.Y., Pauley, B.A., Chan, E.K., and Satoh, M. Anti-MJ/NXP-2 autoantibody specificity in a cohort of adult Italian patients with polymyositis/dermatomyositis. Arthritis Res Ther. 14:R97.

Satoh, M., Chan, J.Y., Ross, S.J., Li, Y., Yamasaki, Y., Yamada, H., Vazquez-Del Mercado, M., Petri, M., Jara, L.J., Saavedra, M.A., Cruz-Reyes, C., Sobel, E.S., Reeves, W.H., Ceribelli, A., and Chan, E.K. Autoantibodies to transcription intermediary factor (TIF)1beta associated with dermatomyositis. Arthritis Res Ther. 14:R79.

Satoh, M., Ceribelli, A., and Chan, E.K. Role of environmental factors in autoantibody production – importance of a detailed analysis in a small cohort. Arthritis Res Ther. 14:109.

Satoh, M., Chan, E.K., Ho, L.A., Rose, K.M., Parks, C.G., Cohn, R.D., Jusko, T.A., Walker, N.J., Germolec, D.R., Whitt, I.Z., Crockett, P.W., Pauley, B.A., Chan, J.Y., Ross, S.J., Birnbaum, L.S., Zeldin, D.C., Miller, F.W. Prevalence and sociodemographic correlates of antinuclear antibodies in the United States. Arthritis Rheum. 64:2319-27.

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. Antivir Ther. DOI: 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.

Satoh, M., Vázquez del Mercado, M., Krzyszczak, M.E., Li, Y., Ceribelli, A., Burlingame, R.W., Webb, T.T., Sobel, E.S., Reeves, W.H., and Chan, E.K. Coexistence of anti-RNA polymerase III and anti-U1RNP antibodies in patients with SLE – Two cases without features of scleroderma. Lupus, 21:68-74.

Krzyszczak, M.E., Li, Y., Ross, S.J., Ceribelli, A., Chan, E.K., Bubb, M.R., Sobel, E.S., Reeves, W.H., and Satoh, M. Gender and ethnicity differences in the prevalence of scleroderma-related autoantibodies. Clin. Rheumatol. 30:1333-9.

Ceribelli, A., Krzyszczak, M.E., Li, Y., Ross, S.J., Chan, J.Y., Chan, E.K., Burlingame, R., Webb, T.T., Bubb, M.R., Sobel, E.S., Reeves, W.H., and Satoh, M. Atypical clinical presentation of a subset of patients with anti-RNA polymerase III – non-scleroderma cases associated with dominant RNA polymerase I reactivity and nucleolar staining. Arthritis Res. Ther. 13:R119.

Satoh, M., Krzyszczak, M.E., Li, Y., Ceribelli, A., Ross, S.J., Chan, E.K., Segal, M.S., Bubb, M.R., Sobel, E.S., and Reeves, W.H. Frequent coexistence of anti-topoisomerase I and anti-U1RNP autoantibodies in African American patients associated with mild skin involvement: a retrospective clinical study. Arthritis Res. Ther. 13:R73.

Satoh, M., Chan, J.Y., Ross, S.J., Ceribelli, A., Cavazzana, I., Franceschini, F., Li, Y., Reeves, W.H., Sobel, E.S., and Chan, E.K. Autoantibodies to survival of motor neuron (SMN) complex in patients with polymyositis – Immunoprecipitation of D-E-F-G without other components of small nuclear ribonucleoproteins. Arthritis Rheum., 63:1972-8.

Satoh, M., Bjerkås, I., Haugarvoll, E., Chan, E.K., Szabo, N.J., Jirillo, E., Poppe, T.T., Sveier, H., Tørud, B., and Koppang, E.O. Polyclonal hypergammaglobulinemia and autoantibody production induced by vaccination in farmed Atlantic salmon. Fish Shellfish Immunol. 30:1080-6.

Ceribelli, A., Tincani, A., Cavazzana, I., Franceschini, F., Cattaneo, R., Pauley, B.A., Chan, J.Y., Chan, E.K., and Satoh, M. Anti-argonaute2 (Ago2/Su) and -Ro antibodies identified by immunoprecipitation in primary anti-phospholipid syndrome (PAPS). Autoimmunity 44:90-7.

2010

Vázquez-Del Mercado, M., Sánchez Orozco, L.V., Pauley, B.A., Chan, J.Y., Chan, E.K., Panduro, A., Maldonado González, M., Jimenez-Luevanos, M.A., Martin Márquez, B.T., Palafox-Sanchez, C.A., Dávalos-Rodríguez, I.P., Salazar-Páramo, M., González Lopez, L., Gámez Nava, J.I., and Satoh, M. Autoantibodies to a miRNA-binding protein Argonaute 2 (Su antigen) in patients with hepatitis C virus infection. Clin. Exp. Rheumatol. 28:842-8.

Ceribelli, A., Cavazzana, I., Franceschini, F., Airò, P., Tincani, A., Cattaneo, R., Pauley, B.A., Chan, E.K., and Satoh, M. Anti-Th/To are common anti-nucleolar autoantibodies in Italian scleroderma patients. J. Rheumatol. 37:2071-5.

Pereira, D.B., Sannes, T., Dodd, S.M., Jensen, S.E., Morgan, L.S., and Chan, E.K. Life stress, negative mood states, and antibodies to heat shock protein 70 in endometrial cancer. Brain, Behavior, and Immunity 24:210-4.

Vázquez-Del Mercado, M., Palafox-Sánchez, C.A., Muñoz-Valle, J.F., Orozco-Barocio, G., Oregon Romero, E., Navarro Hernández, R.E., Salazar-Páramo, M., Chan, J.Y., Chan, E.K., and Satoh, M. High prevalence of autoantibodies to RNA helicase A in Mexican patients with systemic lupus erythematosus. Arthritis Res. Ther. 12:R6.

2009

Kakumanu, P., Sobel, E.S., Narain, S., Li, Y., Akaogi, J., Yamasaki, Y., Segal, M.S., Hahn, P.C., Chan, E.K., Reeves, W.H., and Satoh, M. Citrulline dependence of anti-CCP antibodies in SLE as a marker of deforming/erosive arthritis. J. Rheumatol. 36:2682-90.

Brucato, A., Grava, C., Bortolati, M., Ikeda, K., Milanesi, O., Cimaz, R., Ramoni, V., Vignati, G., Martinelli, S., Sadou, Y., Borghi, A., Tincani, A., Chan, E.K., and Ruffatti, A. Congenital Heart Block not associated with anti-Ro/La antibodies: comparison with anti-Ro/La-positive cases. J. Rheumatol. 36:1744-8.

Nozawa, K., Ikeda, K., Satoh, M., Reeves, W.H., Stewart, C., Li, Y.C., Yen, T.J., Rios, R.M., Takamori, K., Ogawa, H., Sekigawa, I., Takasaki, Y., and Chan, E.K. Autoantibody to NA14 is an independent marker primarily for Sjögren’s syndrome. Frontiers Biosci. 14:3733-9.

Palafox-Sánchez, C.A., Satoh, M., Chan, E.K., Carcamo, W.C., Muñoz-Valle, J.F., Orozco-Barocio, G., Oregón-Romero, E., Navarro-Hernández, R.E., Salazar-Páramo, M., Castañeda, A.C., and Vázquez-Del Mercado, M. Reduced IgG anti-snRNPs autoantibody production in SLE patients with positive IgM anti-cytomegalovirus antibodies. Arthritis Res. Ther. 11:R27.

Llanos, C., Chan, E.K., Li, S., Abadal, G.X., Izmirly, P., Byrne, C., Clancy, R.M., and Buyon, J.P. Antibody Reactivity to α-Enolase in Mothers of Children with Congenital Heart Block. J. Rheumatol. 36:565-9.

2008

Koppang, E.O., Bjerkås, I., Haugarvoll, E., Chan, E.K., Szabo, N.J., Ono, N., Akikusa, B., Jirillo, E., Poppe, T.T., Sveier, H., Tørud, B., and Satoh, M. Vaccination-induced systemic autoimmunity in farmed Atlantic salmon. J. Immunol. 181:4807-14.

Nozawa, K., Fritzler, M.J., Ikeda, K., Takasaki, Y., Satoh, M., and Chan, E.K. Differential anti-Golgi complex autoantibody production in murine lactate dehydrogenase-elevating virus infection. Immunopharmacology and Immunotoxicology 30:13-25.

Kakumanu, P., Yamagata, H., Sobel, E.S., Reeves, W.H., Chan, E.K., and Satoh, M. Patients with pulmonary tuberculosis are frequently positive for anti-CCP antibodies but they also react with unmodified arginine peptide. Arthritis Rheum. 58:1576-81.

2007

Chan, E.K., Fritzler, M.J., Wiik, A., Andrade, L.E.C., Reeves, W.H., Tincani, A., Meroni, P.L., and the IUIS/WHO/AF/CDC committee for the standardization of autoantibodies in rheumatic and related diseases. AutoAbSC.Org – Autoantibody Standardization Committee in 2006. Autoimmunity Rev. 6:577-80.

Bhanji, R.A., Eystathioy, T., Chan, E.K., Bloch, D.B., and Fritzler, M.J. Clinical and serological features of patients with autoantibodies to GW/P Bodies. Clin. Immunol. 125:247-56.

Yamasaki, Y., Narain, S., Yoshida, H., Hernandez, L., Barker, T., Hahn, P.C., Sobel, E.S., Segal, M.S., Richards, H.B., Chan, E.K., Reeves, W.H., and Satoh, M. Autoantibodies to RNA helicase A: A new serological marker of early lupus. Arthritis Rheum. 56:596-604.

2006

Yamasaki, Y., Yamada, H., Nozaki, T., Akaogi, J., Nichols, C., Lyons, R., Loy, A.C., Chan, E.K., Reeves, W.H., and Satoh, M. Unusually high frequency of autoantibodies to PL-7 associated with milder muscle disease in Japanese patients with polymyositis/dermatomyositis. Arthritis Rheum. 54:2004-9.

Yamasaki, Y., Narain, S., Hernandez, L., Barker, T., Ikeda, K., Segal, M.S., Richards, H.B., Chan, E.K., Reeves, W.H., and Satoh, M. Autoantibodies against the replication protein A complex in SLE and other autoimmune diseases. Arthritis Res. Ther. 8:R111.

Yamasaki, Y., Narain, S., Ikeda, K., Honkannen-Scott, M., Hernandez, B.S., Barker, T., Richards, H.B., Chan, E.K., Reeves, W.H., and Satoh, M. Nucleolar staining cannot be used as a screening test for the scleroderma marker anti-RNA polymerase I/III antibodies. Arthritis Rheum. 54:3051-6.

Jakymiw, A., Ikeda, K., Fritzler, M.J., Reeves, W.H., Satoh, M., and Chan, E.K. Autoimmune targeting of key components of RNA interference. Arthritis Res. Ther. 8:R87.

2005

Lu, Y., Ye, P., Chen, S-L., Tan, E.M., and Chan, E.K. Identification of kinectin as a novel Behçet’s disease autoantigen. Arthritis Res. Ther. 7:R1133-9.

Clancy, R.M., Buyon, J.P., Ikeda, K., Nozawa, K., Argyle, D.A., Friedman, D.M., and Chan, E.K. Maternal antibody responses to the 52kD SS-A/Ro p200 peptide and the development of fetal conduction defects. Arthritis Rheum. 52:3079-86.

2004

Nozawa, K., Fritzler, M.J., von Mühlen, C.A., and Chan, E.K. Giantin is the major Golgi autoantigen in human anti-Golgi complex sera. Arthritis Res. Ther. 6:R95-R102.

Key Reviews, Editorials & Book Chapters

2013

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., in press. * co-first author

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.

2012

Satoh, M., Ceribelli, A., and Chan, E.K. Common pathways of autoimmune inflammatory myopathies and genetic neuromuscular disorders. Clin. Rev. Allergy Immunol. 42:16-25.

2009

Satoh, M., Vázquez-Del Mercado, M., and Chan, E.K. Clinical interpretation of antinuclear antibody tests in systemic rheumatic diseases. Mod. Rheum. 19:219-28.

2007

Satoh, M., Chan, E.K., Sobel, E.S., Kimpel, D.L., Yamasaki, Y., Narain, S., Mansoor, R., and Reeves, W.H. Clinical implication of autoantibodies in patients with systemic rheumatic diseases. Expert Rev. Clin. Immunol. 3:721-38.