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1. IKZF1 and UBR4 gene variants drive autoimmunity and Th2 polarization in IgG4-related disease

Author

Liu, Qingxiang, Zheng, Yanyan, Sturmlechner, Ines, Jain, Abhinav, Own, Maryam, Yang, Qiankun, Zhang, Huimin, Vairo, Filippo Pinto e., Cerosaletti, Karen, Buckner, Jane H., Warrington, Kenneth J., Koster, Matthew J., Weyand, Cornelia M., and Goronzy, Jorg J.

Subjects
Thermo Fisher Scientific Inc., Scientific equipment and supplies industry, T cells, Genes, Autoimmunity, Diseases -- Denmark -- United States, Phosphatases, Ubiquitin, B cells, Ligases, Immunoglobulin G, Health care industry
Abstract

IgG4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease whose pathomechanisms remain poorly understood. Here, we identified gene variants in familial IgG4-RD and determined their functional consequences. All 3 affected members of the family shared variants of the transcription factor IKAROS, encoded by IKZF1, and the E3 ubiquitin ligase UBR4. The IKAROS variant increased binding to the FYN promoter, resulting in higher transcription of FYN in T cells. The UBR4 variant prevented the lysosomal degradation of the phosphatase CD45. In the presence of elevated FYN, CD45 functioned as a positive regulatory loop, lowering the threshold for T cell activation. Consequently, T cells from the affected family members were hyperresponsive to stimulation. When transduced with a low-avidity, autoreactive T cell receptor, their T cells responded to the autoantigenic peptide. In parallel, high expression of FYN in T cells biased their differentiation toward Th2 polarization by stabilizing the transcription factor JunB. This bias was consistent with the frequent atopic manifestations in patients with IgG4RD, including the affected family members in the present study. Building on the functional consequences of these 2 variants, we propose a disease model that is not only instructive for IgG4-RD but also for atopic diseases and autoimmune diseases associated with an IKZF1 risk haplotype., Introduction Most autoimmune diseases have a genetic component, with only a few demonstrating monogenic inheritance. Variants in more than 100 genes have been reported to contribute to genetic predisposition to [...]

Published
2024
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3. Patients with ACPA-positive and ACPA-negative rheumatoid arthritis show different serological autoantibody repertoires and autoantibody associations with disease activity

Author

Cunningham, Kevin Y., Hur, Benjamin, Gupta, Vinod K., Arment, Courtney A., Wright, Kerry A., Mason, Thomas G., Peterson, Lynne S., Bekele, Delamo I., Schaffer, Daniel E., Bailey, Marissa L., Delger, Kara E., Crowson, Cynthia S., Myasoedova, Elena, Zeng, Hu, Rodriguez, Moses, Weyand, Cornelia M., Davis, III, John M., and Sung, Jaeyun

Published
2023
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9. List Of Contributors

Author

Abraham, Roshini Sarah, primary, Afzali, Behdad, additional, Águeda, Ana, additional, Akin, Cem, additional, Albanesi, Cristina, additional, Antiochos, Brendan, additional, Aranow, Cynthia, additional, Atkinson, John P., additional, Aune, Thomas M., additional, Babu, Subash, additional, Balko, Justin, additional, Ballow, Mark, additional, Bean, Rachel, additional, Belavgeni, Alexia, additional, Berek, Claudia, additional, Beukelman, Timothy, additional, Beziat, Vivien, additional, Bimler, Lynn, additional, Andrew Bird, J., additional, Blutt, Sarah E., additional, Boguniewicz, Mark, additional, Boisson, Bertrand, additional, Boisson-Dupuis, Stéphanie, additional, Borzova, Elena, additional, Bottazzi, Maria, additional, Boyaka, Prosper N., additional, Bridges, John, additional, Browne, Sarah K., additional, Burks, A. Wesley, additional, Bustamante, Jacinta, additional, Casanova, Jean-Laurent, additional, Chan, Alice, additional, Chan, Edwin S.L., additional, Chatham, Walter Winn, additional, Chinen, Javier, additional, Christopher-Stine, Lisa, additional, Coates, Emily, additional, Cope, Andrew P., additional, Corry, David B., additional, Cosme, Joana, additional, Cron, Randy Q., additional, Dalakas, Marinos C., additional, Dann, Sara M., additional, Das, Satya, additional, Daughety, Molly M., additional, Diamond, Betty, additional, Dispenzieri, Angela, additional, Durham, Stephen R., additional, Eagar, Todd N., additional, Al-Hosni, Michelle, additional, Elitzur, Sarah, additional, Elmets, Craig A., additional, Erkan, Doruk, additional, Fleisher, Thomas A., additional, Fonacier, Luz, additional, Fontenot, Andrew P., additional, Fragoulis, George, additional, Francischetti, Ivo M.B., additional, Freiwald, Tilo, additional, Frew, Anthony J., additional, Fujihashi, Kohtaro, additional, Gadina, Massimo, additional, Gapin, Laurent, additional, Gatt, Moshe E., additional, Gershwin, M. Eric, additional, Gillespie, Susan L., additional, Gordon, Lynn K., additional, Goronzy, Jörg J., additional, Grattan, Clive E., additional, Greenspan, Neil S., additional, Gschwend, Anna, additional, Gustafson, Claire E., additional, Hackett, Tillie-Louise, additional, Hamilton, Robert G., additional, Happe, Myra, additional, Harrison, Leonard C., additional, Helbling, Arthur, additional, Heckmann, Emmaline, additional, Hogquist, Kristin, additional, Hohl, Tobias M., additional, Holland, Steven M., additional, Hotez, Peter J., additional, Houser, Katherine, additional, Huntingdon, Nicholas D., additional, Hwangpo, Tracy, additional, Izraeli, Shai, additional, Jaffe, Elaine S., additional, Jalkanen, Sirpa, additional, Java, Anuja, additional, Johnson, Douglas B., additional, Johnson, Tory, additional, Jordan, Michael B., additional, Joshi, Shyam R., additional, Jouanguy, Emmanuelle, additional, Kaminski, Henry J., additional, Kaufmann, Stefan H.E., additional, Khan, David A., additional, Kheradmand, Farrah, additional, Khokar, Dilawar Singh, additional, Khoury, Paneez, additional, Klein, Bruce S., additional, Klion, Amy D., additional, Kohn, Donald B., additional, Kono, Michihito, additional, Korngold, Robert, additional, Koulouri, Vasiliki, additional, Kuhns, Douglas B., additional, Kulkarni, Hrishikesh S., additional, Kuo, Caroline Y., additional, Kusner, Linda L., additional, Lahouti, Arash, additional, Lane, Laura C., additional, Laurence, Arian, additional, Lee, Joyce S., additional, Lee, S. Thera, additional, Leung, Donald Y.M., additional, Levy, Ofer, additional, Lewis, Dorothy E., additional, Li, Evan, additional, Libby, Peter, additional, Lichtman, Andrew H., additional, Linkermann, Andreas, additional, Lionakis, Michail S., additional, Liszewski, M. Kathryn, additional, Lockshin, Michael D., additional, Priel, Debra Long, additional, Lorenz, Adi Zoref, additional, Ludwig, Ralf J., additional, Luong, Amber, additional, Luqmani, Raashid Ahmed, additional, Mackay, Meggan, additional, Mahr, Alfred, additional, Malley, Tamir, additional, Mannon, Elinor C., additional, Mannon, Peter J., additional, Mannon, Roslyn B., additional, Manns, Michael P., additional, Maresso, Anthony, additional, Matson, Scott M., additional, Mavragani, Clio P., additional, Maynard, Craig L., additional, McDonald, Douglas, additional, Meylan, Françoise, additional, Miller, Stephen D., additional, Mitchell, Anna L., additional, Monos, Dimitri S., additional, Mueller, Scott N., additional, Mulders-Manders, Catharina M., additional, Munshi, Pashna N., additional, Murphy, Philip M., additional, Noel, Pierre, additional, Notarangelo, Luigi D., additional, Nunes-Santos, Cristiane J., additional, Nussbaum, Robert L., additional, Nutman, Thomas B., additional, Nutt, Stephen L., additional, O'Neill, Lorraine, additional, O'Shea, John J., additional, Ortel, Thomas L., additional, Pai, Sung-Yun, additional, Paul, Mary E., additional, Pearce, Simon, additional, Peterson, Erik J., additional, Pittaluga, Stefania, additional, Polverino, Francesca, additional, Puck, Jennifer M., additional, Puel, Anne, additional, Radbruch, Andreas, additional, Rajalingam, Raja, additional, Reece, Stephen T., additional, Reveille, John D., additional, Rich, Robert R., additional, Ridley, Lauren K., additional, Romeo, Andrew R., additional, Rooney, Cliona M., additional, Rosen, Antony, additional, Rosenzweig, Sergio, additional, Rouse, Barry T., additional, Rowley, Scott D., additional, Sahiner, Umit Murat, additional, Sakaguchi, Shimon, additional, Salinas, Whitney, additional, Salmi, Marko, additional, Satola, Sarah, additional, Schechter, Marcos, additional, Schmidt, Enno, additional, Schroeder, Harry W., additional, Schwartzberg, Pamela L., additional, Sciumè, Giuseppe, additional, Segal, Benjamin M., additional, Selmi, Carlo, additional, Sharabi, Amir, additional, Shimano, Kristin Ammon, additional, Sikorski, Patricia M., additional, Simon, Anna, additional, Smith, Gideon P., additional, Song, Joo Y., additional, Stephens, David S., additional, Stephens, Robin, additional, Sun, Michel M., additional, Beretta-Piccoli, Benedetta Terziroli, additional, Tonnus, Wulf, additional, Torgerson, Troy R., additional, Torres, Raul Martin, additional, Treat, Jennifer D., additional, Tsokos, George C., additional, Uzel, Gülbü, additional, Uzonna, Jude E., additional, van der Hilst, Jeroen C.H., additional, van der Meer, Jos W.M., additional, Varga, John, additional, Waldman, Meryl, additional, Weatherhead, Jill, additional, Weiser, Peter, additional, Weyand, Cornelia M., additional, Wigley, Fredrick M., additional, Wing, James B., additional, Wood, Kathryn J., additional, Wilde, Shyra, additional, Xu, Hui, additional, Yusuf, Nabiha, additional, Zerbe, Christa S., additional, Zhang, Qian, additional, Ben-Yehuda, Dina, additional, Zhang, Shen-Ying, additional, and Zieske, Arthur W., additional

Published
2023
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11. Dedication

Author

Rich, Robert R., primary, Fleisher, Thomas A., additional, Schroeder, Harry W., additional, Weyand, Cornelia M., additional, Corry, David B., additional, and Puck, Jennifer M., additional

Published
2023
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12. Preface to the Sixth Edition

Author

Rich, Robert R., primary, Fleisher, Thomas A., additional, Schroeder, Harry W., additional, Weyand, Cornelia M., additional, Corry, David B., additional, and Puck, Jennifer M., additional

Published
2023
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25. “Small Blood Vessels: Big Health Problems?”: Scientific Recommendations of the National Institutes of Health Workshop

Author

Bosetti, Francesca, Galis, Zorina S, Bynoe, Margaret S, Charette, Marc, Cipolla, Marilyn J, del Zoppo, Gregory J, Gould, Douglas, Hatsukami, Thomas S, Jones, Teresa LZ, Koenig, James I, Lutty, Gerard A, Maric‐Bilkan, Christine, Stevens, Troy, Tolunay, H Eser, Koroshetz, Walter, Participants, the Small Blood Vessels Big Health Problems Workshop, Agalliu, Dritan, Antonetti, David A, Boehm, Manfred, Brooks, Claudette E, Caron, Kathleen M, Chilian, William, Daemen, Mat J, D'Amato, Robert, Davis, Thomas P, Ergul, Adviye, Faber, James E, Gomez, Ariel R, Grayson, Peter, Grumbach, Isabella, Grutzendler, Jaime, Gu, Chenghua, Gutterman, David, Hallenbeck, John, Herman, Ira, Humphrey, Jay, Iadecola, Costantino, Inscho, Edward W, Kleinfeld, David, Lo, Eng H, Lopez, Jose A, Macknik, Stephen, Malik, Asrar, Mayadas, Tanya N, McGavern, Dorian, Meininger, Gerald A, Miller, Virginia M, Nedergaard, Maiken, Nelson, Mark T, Peirce‐Cottler, Shayn, Ramadan, Ipolia, Rosenberg, Gary A, Schiffrin, Ernesto L, Searson, Peter, Stachenfeld, Nina, Stan, Radu V, Suarez, Yajaira, Ubogu, Eroboghene E, Vexler, Zinaida S, Weyand, Cornelia M, and Zlokovic, Berislav V

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Good Health and Well Being, Capillaries, Cardiovascular Diseases, Coronary Circulation, Health, Humans, Microcirculation, National Institutes of Health (U.S.), Practice Guidelines as Topic, United States, endothelium, hypertension, imaging, ischemia, microcirculation, remodeling, “Small Blood Vessels: Big Health Problems” Workshop Participants, Cardiorespiratory Medicine and Haematology, Cardiovascular medicine and haematology
Published
2016

30. Large-vessel vasculitis

Author

Pugh, Dan, Karabayas, Maira, Basu, Neil, Cid, Maria C., Goel, Ruchika, Goodyear, Carl S., Grayson, Peter C., McAdoo, Stephen P., Mason, Justin C., Owen, Catherine, Weyand, Cornelia M., Youngstein, Taryn, and Dhaun, Neeraj

Published
2021
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35. Ecto-NTPDase CD39 is a negative checkpoint that inhibits follicular helper cell generation

Author

Cao, Wenqiang, Fang, Fengqin, Gould, Timothy, Li, Xuanying, Kim, Chulwoo, Gustafson, Claire, Lambert, Simon, Weyand, Cornelia M., and Goronzy, Jorg J.

Subjects
Thermo Fisher Scientific Inc., B cells -- Health aspects -- Genetic aspects, Infection -- Genetic aspects, Vaccination -- Health aspects, Antibodies -- Genetic aspects -- Health aspects, Scientific equipment industry -- Genetic aspects -- Health aspects, T cells -- Health aspects -- Genetic aspects, Health care industry
Abstract

Vaccination is a mainstay in preventive medicine, reducing morbidity and mortality from infection, largely by generating pathogen-specific neutralizing antibodies. However, standard immunization strategies are insufficient with increasing age due to immunological impediments, including defects in T follicular helper (Tfh) cells. Here, we found that Tfh generation is inversely linked to the expression of the ecto-NTPDase CD39 that modifies purinergic signaling. The lineage- determining transcription factor BCL6 inhibited CD39 expression, while increased Tfh frequencies were found in individuals with a germline polymorphism preventing transcription of ENTPD1, encoding CD39. In in vitro human and in vivo mouse studies, Tfh generation and germinal center responses were enhanced by reducing CD39 expression through the inhibition of the cAMP/ PKA/p-CREB pathway, or by blocking adenosine signaling downstream of CD39 using the selective adenosine A2a receptor antagonist istradefylline. Thus, purinergic signaling in differentiating T cells can be targeted to improve vaccine responses, in particular in older individuals who have increased CD39 expression., Introduction Vaccination is one of the most successful and safest interventions in modern medicine and has facilitated the extinction of the smallpox virus and the nearly complete eradication of other [...]

Published
2020
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36. Chronic inflammation in the etiology of disease across the life span

Author

Furman, David, Campisi, Judith, Verdin, Eric, Carrera-Bastos, Pedro, Targ, Sasha, Franceschi, Claudio, Ferrucci, Luigi, Gilroy, Derek W., Fasano, Alessio, Miller, Gary W., Miller, Andrew H., Mantovani, Alberto, Weyand, Cornelia M., Barzilai, Nir, Goronzy, Jorg J., Rando, Thomas A., Effros, Rita B., Lucia, Alejandro, Kleinstreuer, Nicole, and Slavich, George M.

Published
2019
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41. Stem-like CD4 + T cells in perivascular tertiary lymphoid structures sustain autoimmune vasculitis

Author

Sato, Yuki, primary, Jain, Abhinav, additional, Ohtsuki, Shozo, additional, Okuyama, Hirohisa, additional, Sturmlechner, Ines, additional, Takashima, Yoshinori, additional, Le, Kevin-Phu C., additional, Bois, Melanie C., additional, Berry, Gerald J., additional, Warrington, Kenneth J., additional, Goronzy, Jörg J., additional, and Weyand, Cornelia M., additional

Published
2023
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42. Use of high-plex data provides novel insights into the temporal artery processes of giant cell arteritis

Author

Parreau, Simon, primary, Molina, Elsa, additional, Dumonteil, Stéphanie, additional, Goulabchand, Radjiv, additional, Naves, Thomas, additional, Bois, Melanie C., additional, Akil, Hussein, additional, Terro, Faraj, additional, Fauchais, Anne-Laure, additional, Liozon, Eric, additional, Jauberteau, Marie-Odile, additional, Weyand, Cornelia M., additional, and Ly, Kim-Heang, additional

Published
2023
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44. Age‐related histopathological findings in temporal arteries

Author

Kendziora, Ryan W, primary, Maleszewski, Joseph J, additional, Lin, Peter T, additional, Aubry, Marie‐Christine, additional, Weyand, Cornelia M, additional, Warrington, Kenneth J, additional, Jenkins, Sarah M, additional, Lo, Ying‐Chun, additional, and Bois, Melanie C, additional

Published
2023
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45. 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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