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1. Index

Author

Anderson, Warwick and Mackay, Ian R.

Published
2014

3. Bibliography

Author

Anderson, Warwick and Mackay, Ian R.

Published
2014

4. Acknowledgments

Author

Anderson, Warwick and Mackay, Ian R.

Published
2014

6. Notes

Author

Anderson, Warwick and Mackay, Ian R.

Published
2014

10. Contents

Author

Anderson, Warwick and Mackay, Ian R.

Published
2014

13. Foreword

Author

Anderson, Warwick and Mackay, Ian R.

Published
2014

17. Ongoing activation of autoantigen‐specific B cells in primary biliary cirrhosis

Author

Zhang, Jun, Zhang, Weici, Leung, Patrick SC, Bowlus, Christopher L, Dhaliwal, Sandeep, Coppel, Ross L, Ansari, Aftab A, Yang, Guo‐Xiang, Wang, Jinjun, Kenny, Thomas P, He, Xiao‐Song, Mackay, Ian R, and Gershwin, M Eric

Subjects
Biomedical and Clinical Sciences, Immunology, Clinical Research, Rare Diseases, Liver Disease, Digestive Diseases, Autoimmune Disease, Chronic Liver Disease and Cirrhosis, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, Aged, 80 and over, Antibody Specificity, Antibody-Producing Cells, Autoantigens, B-Lymphocytes, Case-Control Studies, Dihydrolipoyllysine-Residue Acetyltransferase, Female, Humans, Liver Cirrhosis, Biliary, Male, Middle Aged, Receptors, CCR10, Receptors, CXCR, Young Adult, Medical Biochemistry and Metabolomics, Clinical Sciences, Gastroenterology & Hepatology, Clinical sciences
Abstract

UnlabelledThe serologic hallmark of primary biliary cirrhosis (PBC), the antimitochondrial response to the E2 component of the pyruvate dehydrogenase complex (PDC-E2), has unique features, including continuous high titers of immunoglobulin M (IgM) and IgG reactivity throughout all stages of disease, capable not only of target enzyme inhibition, but also crossreactive with chemical xenobiotics that share molecular homology with the inner lipoyl domain of PDC-E2; such chemicals have been proposed as potential etiological agents. We used flow cytometry and enzyme-linked immunospot assay (ELISPOT) to examine B-cell subsets in 59 subjects, including 28 with PBC, 13 with primary sclerosing cholangitis (PSC), and 18 healthy controls. Strikingly, in PBC, although there were no significant differences in B-cell phenotype subpopulations, 10% of the total IgG and IgA plasmablast population and 23% of the IgM plasmablast population were uniquely reactive with PDC-E2, detected in the CXCR7+ CCR10low plasmablast population. In contrast, plasmablast reactivity to a control antigen, tetanus toxoid, was minimal and similar in all groups. Additionally, we isolated plasmablast-derived polyclonal antibodies and compared reactivity with plasma-derived antibodies and noted a distinct noncirculating tissue source of xenobiotic crossreacting antibodies. The high levels of autoantigen specific peripheral plasmablasts indicate recent activation of naive or memory B cells and a continuous and robust activation. The presence of CXCR7+ CCR10low PDC-E2-specific ASCs suggests a mechanistic basis for the migration of circulating antigen specific plasmablasts to the mucosal epithelial ligands CXCL12 and CCL28.ConclusionOur findings suggest a sustained rigorous B-cell response in PBC, likely activated and perpetuated by cognate autoantigen.

Published
2014

20. List of Contributors

Author

Abramson, Jakub, primary, Ahmed, S. Sohail, additional, Alba, Marco A., additional, Ali, Youssif M., additional, Ambrus, Julian L., additional, Andersson Svärd, Agnes, additional, Aringer, Martin, additional, Assassi, Shervin, additional, Aung, Thanda, additional, Ayzenberg, Ilya, additional, Barker, Robert N., additional, Baxter, Alan G., additional, Betterle, Corrado, additional, Birlea, Stanca A., additional, Björkström, Niklas K., additional, Blair, Paul A., additional, Blüml, Stephan, additional, Bosch, Xavier, additional, Brodsky, Robert A., additional, Bryceson, Yenan T., additional, Burkett, Patrick R., additional, Bussel, James B., additional, Caricchio, Roberto, additional, Casciola-Rosen, Livia, additional, Caturegli, Patrizio, additional, Chaigne-Delalande, Benjamin, additional, Chalan, Paulina, additional, Chatenoud, Lucienne, additional, Cohen, Philip L., additional, Cooper, Megan A., additional, Coppieters, Ken, additional, Crystal, Ronald G., additional, Culton, Donna A., additional, Damato, Valentina, additional, Davidson, Anne, additional, Delfino, Lorenzo, additional, Delves, Peter J., additional, Di Dalmazi, Giulia, additional, Diamond, Betty, additional, Diaz, Luis A., additional, Falk, Ronald J., additional, Fritzler, Marvin J., additional, Gallucci, Stefania, additional, Gangaputra, Sapna, additional, Gelbman, Brian, additional, Gershwin, M. Eric, additional, Gery, Igal, additional, Getts, Daniel R., additional, Gold, Ralf, additional, Goldfarb, Yael, additional, Gong, Jing, additional, Gordon, Siamon, additional, Goronzy, Jörg J., additional, Greer, Judith M., additional, Guazzone, Vanesa A., additional, Guilherme, Luiza, additional, Hafler, David A., additional, Hahn, Bevra H., additional, Hamad, Abdel Rahim A., additional, Hamano, Hideaki, additional, Harrison, Leonard C., additional, Homann, Dirk, additional, Husebye, Eystein S., additional, Jennette, J. Charles, additional, Jones, Richard J., additional, Jordan, Margaret A., additional, Kalil, Jorge, additional, Kawa, Shigeyuki, additional, Kaya, Ziya, additional, Keller, Christian W., additional, King, Nicholas J.C., additional, Kitcharoensakkul, Maleewan, additional, Kiyosawa, Kendo, additional, Königs, Christoph, additional, Kronenberg, Mitchell, additional, Kuchroo, Vijay K., additional, Laurence, Arian, additional, Lee, Eun-Ju, additional, Lehmann, Helmar C., additional, Lernmark, Åke, additional, Lindbladh, Ida, additional, Liu, Zhi, additional, Ljunggren, Hans-Gustaf, additional, Lunardi, Claudio, additional, Lundin, Knut E.A., additional, Lünemann, Jan D., additional, Lunn, Michael P.T., additional, Lustig, Livia, additional, Mackay, Charles R., additional, Mackay, Ian R., additional, Malattia, Clara, additional, Martinez-Pomares, Luisa, additional, Martini, Alberto, additional, Mauri, Claudia, additional, McCombe, Pamela A., additional, Melchers, Fritz, additional, Mieli-Vergani, Giorgina, additional, Miller, Frederick W., additional, Miller, Stephen D., additional, Mizui, Masayuki, additional, Mjösberg, Jenny, additional, Münz, Christian, additional, Nijjar, Jagtar Singh, additional, Norris, David A., additional, Oleinika, Kristine, additional, Oppenheim, Joost J., additional, Pawlak, Mathias, additional, Peligero-Cruz, Cristina, additional, Peters, Anneli, additional, Peterson, Pärt, additional, Pitarokoili, Kalliopi, additional, Presotto, Fabio, additional, Puccetti, Antonio, additional, Rabb, Hamid, additional, Raczek, Patricia, additional, Rahman, M. Jubayer, additional, Ramos-Casals, Manuel, additional, Rose, Noel R., additional, Rosen, Antony, additional, Sadasivam, Mohanraj, additional, Schiffenbauer, Adam, additional, Schwaeble, Wilhelm J., additional, Sen, H. Nida, additional, Serota, Marc, additional, Sheikh, Kazim A., additional, Shoenfeld, Yehuda, additional, Shovman, Ora, additional, Sieper, Joachim, additional, Silverstein, Arthur M., additional, Sim, Robert B., additional, Smith, Kenneth G C, additional, Smolen, Josef S., additional, Sollid, Ludvig M., additional, Spiteri, Alanna, additional, Steinman, Lawrence, additional, Stone, John H., additional, Syrbe, Uta, additional, Tamhaney, Ami, additional, Tanaka, Atsushi, additional, Taneja, Veena, additional, Tarbell, Kristin V., additional, Tinazzi, Elisa, additional, Tiong, Benedict K., additional, Toh, Ban-Hock, additional, Tsokos, George C., additional, Tung, Kenneth S.K., additional, Varga, John, additional, Vergani, Diego, additional, Vickers, Mark A., additional, Viegas, Stuart, additional, Vincent, Angela, additional, von Herrath, Matthias, additional, Weetman, Anthony P., additional, Weinstock, Joel V., additional, Wentworth, John M., additional, Wesley, Sarah, additional, Weyand, Cornelia M., additional, Wingender, Gerhard, additional, Winter, Michael W., additional, Zanchetta, Renato, additional, and Zouali, Moncef, additional

Published
2020
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21. Hepatitis

Author

Vergani, Diego, primary, Mackay, Ian R., additional, and Mieli-Vergani, Giorgina, additional

Published
2020
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24. NOD.c3c4 congenic mice develop autoimmune biliary disease that serologically and pathogenetically models human primary biliary cirrhosis

Author

Irie, Junichiro, Wu, Yuehong, Wicker, Linda S, Rainbow, Daniel, Nalesnik, Michael A, Hirsch, Raphael, Peterson, Laurence B, Leung, Patrick SC, Cheng, Chunmei, Mackay, Ian R, Gershwin, M Eric, and Ridgway, William M

Subjects
Biomedical and Clinical Sciences, Immunology, Biotechnology, Chronic Liver Disease and Cirrhosis, Rare Diseases, Autoimmune Disease, Digestive Diseases, Liver Disease, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Adoptive Transfer, Animals, Autoantibodies, Autoimmune Diseases, CD3 Complex, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cholangitis, Chromosome Mapping, Dihydrolipoyllysine-Residue Acetyltransferase, Disease Models, Animal, Granuloma, Humans, Inflammation, Liver Cirrhosis, Biliary, Liver Cirrhosis, Experimental, Mice, Mice, Congenic, Mice, Inbred NOD, Mice, SCID, Mice, Transgenic, Mitochondrial Proteins, Protein Structure, Tertiary, Quantitative Trait Loci, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

Primary biliary cirrhosis (PBC) is an autoimmune disease with a strong genetic component characterized by biliary ductular inflammation with eventual liver cirrhosis. The serologic hallmark of PBC is antimitochondrial antibodies that react with the pyruvate dehydrogenase complex, targeting the inner lipoyl domain of the E2 subunit (anti-PDC-E2). Herein we demonstrate that NOD.c3c4 mice congenically derived from the nonobese diabetic strain develop an autoimmune biliary disease (ABD) that models human PBC. NOD.c3c4 (at 9-10 wk, before significant biliary pathology) develop antibodies to PDC-E2 that are specific for the inner lipoyl domain. Affected areas of biliary epithelium are infiltrated with CD3+, CD4+, and CD8+ T cells, and treatment of NOD.c3c4 mice with monoclonal antibody to CD3 protects from ABD. Furthermore, NOD.c3c4-scid mice develop disease after adoptive transfer of splenocytes or CD4+ T cells, demonstrating a central role for T cells in pathogenesis. Histological analysis reveals destructive cholangitis, granuloma formation, and eosinophilic infiltration as seen in PBC, although, unlike PBC, the extrahepatic biliary ducts are also affected. Using a congenic mapping approach, we define the first ABD (Abd) locus, Abd1. These results identify the NOD.c3c4 mouse as the first spontaneous mouse model of PBC.

Published
2006

25. Introduction

Author

Mackay, Ian R., Gershwin, M. Eric, editor, Vierling, John M., editor, and Manns, Michael P., editor

Published
2014
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27. Cofactor-dependent conformational heterogeneity of GAD65 and its role in autoimmunity and neurotransmitter homeostasis

Author

Kass, Itamar, Hoke, David E., Costa, Mauricio G. S., Reboul, Cyril F., Porebski, Benjamin T., Cowieson, Nathan P., Leh, Hervé, Pennacchietti, Eugenia, McCoey, Julia, Kleifeld, Oded, Voltattorni, Carla Borri, Langley, David, Roome, Brendan, Mackay, Ian R., Christ, Daniel, Perahia, David, Buckle, Malcolm, Paiardini, Alessandro, De Biase, Daniela, and Buckle, Ashley M.

Published
2014
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29. Autoantigenicity of Actin

Author

Mackay, Ian R., Martinez-Neira, Roberto, Whittingham, Senga, Nicolau, Dan, Toh, Ban-Hock, Atassi, M. Zouhair, editor, dos Remedios, Cristobal G., editor, and Chhabra, Deepak, editor

Published
2008
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31. Evaluating the Effects of Chronological Age and Sentence Duration on Degree of Perceived Foreign Accent

Author

Mackay, Ian R. A., Flege, James E., and Imai, Satomi

Abstract

Immigrants' age of arrival (AOA) in a country where a second language (L2) must be learned has consistently been shown to affect the degree of perceived L2 foreign accent. Although the effect of AOA appears strong, AOA is typically correlated with other variables that might influence degree of foreign accent. This study examined the pronunciation of English by native Italian immigrants to Canada who differed in AOA. As in previous research, those who arrived as young adults (late learners) were somewhat older at the time of testing, and produced somewhat longer English sentences, than those who arrived in Canada when they were children (early learners). The results of Experiment 1 showed that the greater chronological age of early than late learners was not responsible for the late learners' stronger foreign accents. Experiment 2 suggested that the late learners' longer L2 sentences were not responsible for observed early-late foreign accent differences. A principle components analysis revealed that variation in AOA and language use, but not chronological age or sentence duration, accounted for a significant amount of variance in the foreign accent ratings. The findings of the study were interpreted to mean that AOA effects on foreign accent are due to the development of the native language phonetic system rather than to maturational constraints on L2 speech learning.

Published
2006
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33. Perceiving Vowels in a Second Language

Author

Flege, James Emil and MacKay, Ian R. A.

Abstract

This study examines the perception of English vowels by native speakers of Italian. In two preliminary experiments, Italian university students who had lived in Canada for 3 months were found to have difficulty discriminating because they often identified both members of each contrast as instances of a single Italian vowel. The participants in two other experiments, long-time residents of Canada, were assigned to groups based on their age of arrival in Canada from Italy (early vs. late) and percentage of first language (L1) use (high L1 use vs. low L1 use). Experiment 3 focused on the discrimination of, and experiment 4 examined the discrimination of correct from incorrect realizations of. In both experiments, the early learners obtained higher discrimination scores than the late learners, and low-L1-use participants obtained higher scores than high-L1-use participants. Most important, the early learners who used Italian often (early high), but not the early learners who used Italian seldom (early low), were found to differ from native speakers of English in perceiving English vowels. These results suggest two important conclusions regarding second language (L2) perceptual learning: Learning an L2 in childhood does not guarantee a nativelike perception of L2 vowels, nor does the establishment of a sound system for the L1 preclude a functionally nativelike perception of L2 vowels. Another important finding is that, although the late learners generally perceived English vowels less accurately than the early learners, some perceived them accurately.

Published
2004

34. Assessing Bilingual Dominance.

Author

Flege, James Emil, Mackay, Ian R. A., and Piske, Thorsten

Abstract

Used two methods to assess bilingual dominance in four groups of Italian-English bilinguals. Ratios were derived from bilinguals' self-rating of ability to speak and understand Italian compared to English. Dominance in Italian was associated with a relatively high level of performance in Italian (assessed in a translation task) and relatively poor performance in English (assessed by measuring strength of foreign accents). (Author/VWL)

Published
2002

35. Factors Affecting the Recognition of Words in a Second Language.

Author

Flege, James E., Meador, Diane, and MacKay, Ian R. A.

Abstract

Examined the recognition of English words by groups of native speakers of Italian who differed in age of arrival in Canada and amount of continued native language use. The dependent variable was the number of words correctly repeated in English sentences presented in noise. Significantly higher word recognition scores were obtained for early bilinguals, and for early bilinguals who used Italian seldom. (Author/VWL)

Published
2000

44. List of Contributors

Author

Agmon-Levin, Nancy, primary, Ahmed, S. Sohail, additional, Ali, Youssif M., additional, Aringer, Martin, additional, Bach, Jean-François, additional, Barker, Jennifer, additional, Barker, Robert N., additional, Baxter, Alan G., additional, Betterle, Corrado, additional, Birlea, Stanca A., additional, Björkström, Niklas K., additional, Blair, Paul A., additional, Bobik, Alex, additional, Borazan, Nabeel H., additional, Bosch, Xavier, additional, Brodsky, Robert A., additional, Bryceson, Yenan T., additional, Burkett, Patrick R., additional, Bussel, James B., additional, Butzkueven, Helmut, additional, Caricchio, Roberto, additional, Casciola-Rosen, Livia, additional, Caturegli, Patrizio, additional, Chatenoud, Lucienne, additional, Cohen, Philip L., additional, Coppieters, Ken, additional, Crome, Sarah Q., additional, Crystal, Ronald G., additional, Culton, Donna A., additional, Dalal, Monica D., additional, David, Chella S., additional, Davidson, Anne, additional, Delli, Ahmed J., additional, Delves, Peter J., additional, Denmark, Vera Kandror, additional, Diamond, Betty, additional, Diaz, Luis A., additional, Eaton, John E., additional, Eisenbarth, George S., additional, Falk, Ronald J., additional, Field, Judith, additional, Fleisher, Thomas A., additional, Fragoulis, George E., additional, Fritzler, Marvin J., additional, Furst, Daniel E., additional, Gallucci, Stefania, additional, Gelbman, Brian, additional, Eric Gershwin, M., additional, Getts, Daniel R., additional, Getts, Meghann Teague, additional, Gianani, Roberto, additional, Gleeson, Paul A., additional, Goding, James W., additional, Gordon, Siamon, additional, Goronzy, Jörg J., additional, Greer, Judith M., additional, Gruson, Berengere, additional, Guilherme, L., additional, Gutenberg, Angelika, additional, Hafler, David A., additional, Hahn, Bevra H., additional, Hamano, Hideaki, additional, Hamilton, Sara R., additional, Harrison, Leonard C., additional, Hernandez, Amanda L., additional, Husebye, Eystein, additional, Charles Jennette, J., additional, Jones, Richard J., additional, Jordan, Margaret A., additional, Kalil, J., additional, Königs, Christoph, additional, Kawa, Shigeyuki, additional, Kaya, Ziya, additional, King, Jennifer K., additional, King, Nicholas J.C., additional, Kiyosawa, Kendo, additional, Kronenberg, Mitchell, additional, Kuchroo, Vijay K., additional, Kyaw, Tin, additional, Lünemann, Jan, additional, Lahita, Robert G., additional, Lalezari, Parviz, additional, Lambert, Paul-Henri, additional, Lancaster, Eric, additional, Laurence, Arian, additional, Lee, Youjin, additional, Lenardo, Michael, additional, Lernmark, Åke, additional, Levinson, Arnold I., additional, Lindor, Keith D., additional, Liu, Zhi, additional, Ljunggren, Hans-Gustaf, additional, Lunardi, Claudio, additional, Lundin, Knut E.A., additional, Lunn, Michael P.T., additional, Lupi, Isabella, additional, Lustig, Livia, additional, Münz, Christian, additional, Mackay, Charles R., additional, Mackay, Ian R., additional, Malattia, Clara, additional, Mangalam, Ashutosh, additional, Martini, Alberto, additional, Mauri, Claudia, additional, Mavragani, Clio P., additional, Mayer, Lloyd, additional, McCombe, Pamela A., additional, Melchers, Fritz, additional, Mieli-Vergani, Giorgina, additional, Miller, Frederick W., additional, Miller, Stephen D., additional, Mizui, Masayuki, additional, Mjösberg, Jenny, additional, Moutsopoulos, Haralampos M., additional, Norris, David A., additional, Nussenblatt, Robert B., additional, O’Connor, Kevin C., additional, Ohashi, Pamela S., additional, O’Keeffe, Meredith, additional, Oliveira, Joao Bosco, additional, Oppenheim, Joost J., additional, Perez-Arroyo, Alicia, additional, Peters, Anneli, additional, Peterson, Pärt, additional, Plüddemann, Annette, additional, Posner, Jerome B., additional, Preston, Gloria A., additional, Puccetti, Antonio, additional, Radford, Kristen, additional, Ramos-Casals, Manuel, additional, Rao, V. Koneti, additional, Rauschkolb, Paula K., additional, Reddy, Venkat, additional, Redlich, Kurt, additional, Rival, Claudia, additional, Rose, Noel R., additional, Rosen, Antony, additional, Schrader, John W., additional, Schwaeble, Wilhelm J., additional, Selmi, Carlo, additional, Nida Sen, H., additional, Serota, Marc, additional, Sheikh, Kazim A., additional, Shoenfeld, Yehuda, additional, Shortman, Ken, additional, Sieper, Joachim, additional, Silverstein, Arthur M., additional, Sim, Robert B., additional, Simon, Anna, additional, Smolen, Josef S., additional, Sollid, Ludvig M., additional, Stoffels, Monique, additional, Su, Helen, additional, Syrbe, Uta, additional, Talwalkar, Jayant A., additional, Taneja, Veena, additional, Tincani, Angela, additional, Tipping, Peter, additional, Toh, Ban-Hock, additional, Tsokos, George C., additional, Tu, Eric, additional, Tung, Kenneth S.K., additional, van Driel, Ian R., additional, Vergani, Diego, additional, Vickers, Mark A., additional, Viegas, Stuart, additional, Vincent, Angela, additional, von Andrian, Ulrich H., additional, Herrath, Matthias von, additional, Weetman, Anthony P., additional, Wentworth, John M., additional, Weyand, Cornelia M., additional, Wingender, Gerhard, additional, Zanchetta, Renato, additional, and Zouali, Moncef, additional

Published
2014
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46. Hepatitis

Author

Vergani, Diego, primary, Mackay, Ian R., additional, and Mieli-Vergani, Giorgina, additional

Published
2014
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