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1. A unified metric of human immune health

Author

Sparks, Rachel, Rachmaninoff, Nicholas, Lau, William W., Hirsch, Dylan C., Bansal, Neha, Martins, Andrew J., Chen, Jinguo, Liu, Candace C., Cheung, Foo, Failla, Laura E., Biancotto, Angelique, Fantoni, Giovanna, Sellers, Brian A., Chawla, Daniel G., Howe, Katherine N., Mostaghimi, Darius, Farmer, Rohit, Kotliarov, Yuri, Calvo, Katherine R., Palmer, Cindy, Daub, Janine, Foruraghi, Ladan, Kreuzburg, Samantha, Treat, Jennifer D., Urban, Amanda K., Jones, Anne, Romeo, Tina, Deuitch, Natalie T., Moura, Natalia Sampaio, Weinstein, Barbara, Moir, Susan, Ferrucci, Luigi, Barron, Karyl S., Aksentijevich, Ivona, Kleinstein, Steven H., Townsley, Danielle M., Young, Neal S., Frischmeyer-Guerrerio, Pamela A., Uzel, Gulbu, Pinto-Patarroyo, Gineth Paola, Cudrici, Cornelia D., Hoffmann, Patrycja, Stone, Deborah L., Ombrello, Amanda K., Freeman, Alexandra F., Zerbe, Christa S., Kastner, Daniel L., Holland, Steven M., and Tsang, John S.

Published
2024
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2. Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency

Author

Oda, Hirotsugu, Manthiram, Kalpana, Chavan, Pallavi Pimpale, Rieser, Eva, Veli, Önay, Kaya, Öykü, Rauch, Charles, Nakabo, Shuichiro, Kuehn, Hye Sun, Swart, Mariël, Wang, Yanli, Çelik, Nisa Ilgim, Molitor, Anne, Ziaee, Vahid, Movahedi, Nasim, Shahrooei, Mohammad, Parvaneh, Nima, Alipour-olyei, Nasrin, Carapito, Raphael, Xu, Qin, Preite, Silvia, Beck, David B., Chae, Jae Jin, Nehrebecky, Michele, Ombrello, Amanda K., Hoffmann, Patrycja, Romeo, Tina, Deuitch, Natalie T., Matthíasardóttir, Brynja, Mullikin, James, Komarow, Hirsh, Stoddard, Jennifer, Niemela, Julie, Dobbs, Kerry, Sweeney, Colin L., Anderton, Holly, Lawlor, Kate E., Yoshitomi, Hiroyuki, Yang, Dan, Boehm, Manfred, Davis, Jeremy, Mudd, Pamela, Randazzo, Davide, Tsai, Wanxia Li, Gadina, Massimo, Kaplan, Mariana J., Toguchida, Junya, Mayer, Christian T., Rosenzweig, Sergio D., Notarangelo, Luigi D., Iwai, Kazuhiro, Silke, John, Schwartzberg, Pamela L., Boisson, Bertrand, Casanova, Jean-Laurent, Bahram, Seiamak, Rao, Anand Prahalad, Peltzer, Nieves, Walczak, Henning, Lalaoui, Najoua, Aksentijevich, Ivona, and Kastner, Daniel L.

Published
2024
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4. Venous and arterial thrombosis in patients with VEXAS syndrome

Author

Kusne, Yael, Ghorbanzadeh, Atefeh, Dulau-Florea, Alina, Shalhoub, Ruba, Alcedo, Pedro E., Nghiem, Khanh, Ferrada, Marcela A., Hines, Alexander, Quinn, Kaitlin A., Panicker, Sumith R., Ombrello, Amanda K., Reichard, Kaaren, Darden, Ivana, Goodspeed, Wendy, Durrani, Jibran, Wilson, Lorena, Olteanu, Horatiu, Lasho, Terra, Kastner, Daniel L., Warrington, Kenneth J., Mangaonkar, Abhishek, Go, Ronald S., Braylan, Raul C., Beck, David B., Patnaik, Mrinal M., Young, Neal S., Calvo, Katherine R., Casanegra, Ana I., Grayson, Peter C., Koster, Matthew J., Wu, Colin O., Kanthi, Yogendra, Patel, Bhavisha A., Houghton, Damon E., and Groarke, Emma M.

Published
2024
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5. PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants

Author

Abbott, Jordan K., Aldave Becerra, Juan Carlos, Allenspach, Eric J., Assing, Kristian, Atkinson, T. Prescott, Bargir, Umair A., Baxter, Sarah K., Bergerson, Jenna R.E., Bista, Ranjan, Blanche, Stephane, Buckley, Lenore M., Butte, Manish, Carcamo, Benjamin, Chandrakala, Shanmukhaiah, Chen, Karin, Chervinskiy, Sheva, Chinn, Ivan K., Chong, Hey J., Coffey, Kara E., Copland, Andrew P., Cowen, Edward W., Cros, Guilhem, De Bruycker, Jean Jacques, Teresa de la Morena, Maria, Ehlayel, Mohammed, Forbes Satter, Lisa R., Gelfand, Erwin W., Gilliaux, Olivier, Glover, Sara C., Gorman, Mark, Griffin, Thomas A., Grimbacher, Bodo, Gru, Alejandro A., Haddad, Elie, Hadjadj, Jerome, Hajjar, Joud, Hauck, Fabian, Hautala, Timo, Holland, Steven M., Hsieh, Elena W.Y., Hsu, Florence Ida, Jacquemin, Emmanuel, Jindal, Ankur Kumar, Kahn, Stacy A., Keller, Michael D., Kobayashi, Roger H., Krupski, Christa, Larkin, Allyson, Lawrence, Monica G., Madkaikar, Manisha, Malphettes, Marion, Martelius, Timi, Mehta, Mehek, Metcalfe, Dean D., Meyts, Isabelle, Nannapaneni, Naveen, Ocejo Vinyals, J. Gonzalo, Olivier, Kenneth, Ombrello, Amanda K., Orange, Jordan S., Rabinovitch, Nathan, Rauscher, Christine K., Redfern, Ann, Reynolds, Paul R., Rieux-Laucat, Frederic, Secord, Elizabeth, Seeborg, Filiz O., Seppänen, Mikko R.J., Sereti, Irini, Shin, Daniel S., Shin, Junghee J., Snapper, Scott B., Suri, Deepti, Tangcheewinsirikul, Sirikarn, Thatayatikom, Akaluck, Torgerson, Troy, Touzot, Fabien, Uzel, Gulbu, Varjosalo, Markku, Vasconcelos, Dewton F.P., von Bernuth, Horst, Walsh, Thomas, Walter, Jolan E., Ward, Brant R., Wittkowski, Helmut, Wysocki, Christian A., Baysac, Kathleen, Sun, Guangping, Nakano, Hiroto, Schmitz, Elizabeth G., Cruz, Anthony C., Fisher, Charles, Bailey, Alexis C., Mace, Emily, Milner, Joshua D., and Ombrello, Michael J.

Published
2024
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6. Early activation of inflammatory pathways in UBA1-mutated hematopoietic stem and progenitor cells in VEXAS

Author

Wu, Zhijie, Gao, Shouguo, Gao, Qingyan, Patel, Bhavisha A., Groarke, Emma M., Feng, Xingmin, Manley, Ash Lee, Li, Haoran, Ospina Cardona, Daniela, Kajigaya, Sachiko, Alemu, Lemlem, Quinones Raffo, Diego, Ombrello, Amanda K., Ferrada, Marcela A., Grayson, Peter C., Calvo, Katherine R., Kastner, Daniel L., Beck, David B., and Young, Neal S.

Published
2023
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7. Spectrum of clonal hematopoiesis in VEXAS syndrome

Author

Gutierrez-Rodrigues, Fernanda, Kusne, Yael, Fernandez, Jenna, Lasho, Terra, Shalhoub, Ruba, Ma, Xiaoyang, Alessi, Hugh, Finke, Christy, Koster, Matthew J., Mangaonkar, Abhishek, Warrington, Kenneth J., Begna, Kebede, Xie, Zhuoer, Ombrello, Amanda K., Viswanatha, David, Ferrada, Marcela, Wilson, Lorena, Go, Ronald, Kourelis, Taxiarchis, Reichard, Kaaren, Olteanu, Horatiu, Darden, Ivana, Hironaka, Dalton, Alemu, Lemlem, Kajigaya, Sachiko, Rosenzweig, Sofia, Calado, Rodrigo T., Groarke, Emma M., Kastner, Daniel L., Calvo, Katherine R., Wu, Colin O., Grayson, Peter C., Young, Neal S., Beck, David B., Patel, Bhavisha A., and Patnaik, Mrinal M.

Published
2023
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8. Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease

Author

Lalaoui, Najoua, Boyden, Steven E, Oda, Hirotsugu, Wood, Geryl M, Stone, Deborah L, Chau, Diep, Liu, Lin, Stoffels, Monique, Kratina, Tobias, Lawlor, Kate E, Zaal, Kristien JM, Hoffmann, Patrycja M, Etemadi, Nima, Shield-Artin, Kristy, Biben, Christine, Tsai, Wanxia Li, Blake, Mary D, Kuehn, Hye Sun, Yang, Dan, Anderton, Holly, Silke, Natasha, Wachsmuth, Laurens, Zheng, Lixin, Moura, Natalia Sampaio, Beck, David B, Gutierrez-Cruz, Gustavo, Ombrello, Amanda K, Pinto-Patarroyo, Gineth P, Kueh, Andrew J, Herold, Marco J, Hall, Cathrine, Wang, Hongying, Chae, Jae Jin, Dmitrieva, Natalia I, McKenzie, Mark, Light, Amanda, Barham, Beverly K, Jones, Anne, Romeo, Tina M, Zhou, Qing, Aksentijevich, Ivona, Mullikin, James C, Gross, Andrew J, Shum, Anthony K, Hawkins, Edwin D, Masters, Seth L, Lenardo, Michael J, Boehm, Manfred, Rosenzweig, Sergio D, Pasparakis, Manolis, Voss, Anne K, Gadina, Massimo, Kastner, Daniel L, and Silke, John

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Biodefense, Prevention, Rare Diseases, Vaccine Related, 1.1 Normal biological development and functioning, Underpinning research, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Animals, Caspase 3, Caspase 8, Female, Hereditary Autoinflammatory Diseases, Humans, MAP Kinase Kinase Kinases, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutation, Pedigree, Receptor-Interacting Protein Serine-Threonine Kinases, General Science & Technology
Abstract

RIPK1 is a key regulator of innate immune signalling pathways. To ensure an optimal inflammatory response, RIPK1 is regulated post-translationally by well-characterized ubiquitylation and phosphorylation events, as well as by caspase-8-mediated cleavage1-7. The physiological relevance of this cleavage event remains unclear, although it is thought to inhibit activation of RIPK3 and necroptosis8. Here we show that the heterozygous missense mutations D324N, D324H and D324Y prevent caspase cleavage of RIPK1 in humans and result in an early-onset periodic fever syndrome and severe intermittent lymphadenopathy-a condition we term 'cleavage-resistant RIPK1-induced autoinflammatory syndrome'. To define the mechanism for this disease, we generated a cleavage-resistant Ripk1D325A mutant mouse strain. Whereas Ripk1-/- mice died postnatally from systemic inflammation, Ripk1D325A/D325A mice died during embryogenesis. Embryonic lethality was completely prevented by the combined loss of Casp8 and Ripk3, but not by loss of Ripk3 or Mlkl alone. Loss of RIPK1 kinase activity also prevented Ripk1D325A/D325A embryonic lethality, although the mice died before weaning from multi-organ inflammation in a RIPK3-dependent manner. Consistently, Ripk1D325A/D325A and Ripk1D325A/+ cells were hypersensitive to RIPK3-dependent TNF-induced apoptosis and necroptosis. Heterozygous Ripk1D325A/+ mice were viable and grossly normal, but were hyper-responsive to inflammatory stimuli in vivo. Our results demonstrate the importance of caspase-mediated RIPK1 cleavage during embryonic development and show that caspase cleavage of RIPK1 not only inhibits necroptosis but also maintains inflammatory homeostasis throughout life.

Published
2020

9. Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis

Author

Ferrada, Marcela A., Savic, Sinisa, Cardona, Daniela Ospina, Collins, Jason C., Alessi, Hugh, Gutierrez-Rodrigues, Fernanda, Kumar, Dinesh Babu Uthaya, Wilson, Lorena, Goodspeed, Wendy, Topilow, James S., Paik, Julie J., Poulter, James A., Kermani, Tanaz A., Koster, Matthew J., Warrington, Kenneth J., Cargo, Catherine, Tattersall, Rachel S., Duncan, Christopher J.A., Cantor, Anna, Hoffmann, Patrycja, Payne, Elspeth M., Bonnekoh, Hanna, Krause, Karoline, Cowen, Edward W., Calvo, Katherine R., Patel, Bhavisha A., Ombrello, Amanda K., Kastner, Daniel L., Young, Neal S., Werner, Achim, Grayson, Peter C., and Beck, David B.

Published
2022
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10. DADA2

Author

Ombrello, Amanda K., Goldbach-Mansky, Raphaela, Section editor, Orange, Jordan Scott, editor, Chinen, Javier, editor, MacKay, Ian R., Series Editor, and Rose, Noel R., Series Editor

Published
2020
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11. Common genetic susceptibility loci link PFAPA syndrome, Behçet’s disease, and recurrent aphthous stomatitis

Author

The Genomic Ascertainment Cohort, Manthiram, Kalpana, Preite, Silvia, Dedeoglu, Fatma, Demir, Selcan, Ozen, Seza, Edwards, Kathryn M., Lapidus, Sivia, Katz, Alexander E., Feder, Henry M., Lawton, Maranda, Licameli, Greg R., Wright, Peter F., Le, Julie, Barron, Karyl S., Ombrello, Amanda K., Barham, Beverly, Romeo, Tina, Jones, Anne, Srinivasalu, Hemalatha, Mudd, Pamela A., DeBiasi, Roberta L., Gül, Ahmet, Marshall, Gary S., Jones, Olcay Y., Chandrasekharappa, Settara C., Stepanovskiy, Yuriy, Ferguson, Polly J., Schwartzberg, Pamela L., Remmers, Elaine F., and Kastner, Daniel L.

Published
2020

12. Quantitative analysis of the natural history of prolidase deficiency: description of 17 families and systematic review of published cases

Author

Rossignol, Francis, Duarte Moreno, Marvid S., Benoist, Jean-François, Boehm, Manfred, Bourrat, Emmanuelle, Cano, Aline, Chabrol, Brigitte, Cosson, Claudine, Díaz, José Luís Dapena, D’Harlingue, Arthur, Dimmock, David, Freeman, Alexandra F., García, María Tallón, Garganta, Cheryl, Goerge, Tobias, Halbach, Sara S., de Laffolie, Jan, Lam, Christina T., Martin, Ludovic, Martins, Esmeralda, Meinhardt, Andrea, Melki, Isabelle, Ombrello, Amanda K., Pérez, Noémie, Quelhas, Dulce, Scott, Anna, Slavotinek, Anne M., Soares, Ana Rita, Stein, Sarah L., Süßmuth, Kira, Thies, Jenny, Ferreira, Carlos R., and Schiff, Manuel

Published
2021
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13. Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1

Author

Obiorah, Ifeyinwa Emmanuela, Patel, Bhavisha A., Groarke, Emma M., Wang, Weixin, Trick, Megan, Ombrello, Amanda K., Ferrada, Marcela A., Wu, Zhijie, Gutierrez-Rodrigues, Fernanda, Lotter, Jennifer, Wilson, Lorena, Hoffmann, Patrycja, Cardona, Daniela Ospina, Patel, Nisha, Dulau-Florea, Alina, Kastner, Daniel L., Grayson, Peter C., Beck, David B., Young, Neal S., and Calvo, Katherine R.

Published
2021
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16. Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome

Author

Hines, Melissa R., Knight, Tristan E., McNerney, Kevin O., Leick, Mark B., Jain, Tania, Ahmed, Sairah, Frigault, Matthew J., Hill, Joshua A., Jain, Michael D., Johnson, William T., Lin, Yi, Mahadeo, Kris M., Maron, Gabriela M., Marsh, Rebecca A., Neelapu, Sattva S., Nikiforow, Sarah, Ombrello, Amanda K., Shah, Nirav N., Talleur, Aimee C., Turicek, David, Vatsayan, Anant, Wong, Sandy W., Maus, Marcela V., Komanduri, Krishna V., Berliner, Nancy, Henter, Jan-Inge, Perales, Miguel-Angel, Frey, Noelle V., Teachey, David T., Frank, Matthew J., and Shah, Nirali N.

Published
2023
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17. Perforin-deficient CAR T cells recapitulate late-onset inflammatory toxicities observed in patients

Author

Ishii, Kazusa, Pouzolles, Marie, Chien, Christopher D., Erwin-Cohen, Rebecca A., Kohler, M. Eric, Qin, Haiying, Lei, Haiyan, Kuhn, Skyler, Ombrello, Amanda K., Dulau-Florea, Alina, Eckhaus, Michael A., Shalabi, Haneen, Yates, Bonnie, Lichtenstein, Daniel A., Zimmermann, Valerie S., Kondo, Taisuke, Shern, Jack F., Young, Howard A., Taylor, Naomi, Shah, Nirali N., and Fry, Terry J.

Subjects
United States. National Cancer Institute, United States. Recombinant DNA Advisory Committee, Antigens -- Health aspects -- Comparative analysis, Cytokines -- Comparative analysis -- Health aspects, B cells -- Health aspects -- Comparative analysis, Blinatumomab -- Comparative analysis -- Health aspects, Inflammation -- Health aspects -- Comparative analysis, Toxicity -- Comparative analysis -- Health aspects, Leukemia -- Health aspects -- Comparative analysis, T cells -- Comparative analysis -- Health aspects, Health care industry
Abstract

Late-onset inflammatory toxicities resembling hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) occur after chimeric antigen receptor T cell (CAR T cell) infusion and represent a therapeutic challenge. Given the established link between perforin deficiency and primary HLH, we investigated the role of perforin in anti-CD19 CAR T cell efficacy and HLH-like toxicities in a syngeneic murine model. Perforin contributed to both [CD8.sup.+] and [CD4.sup.+] CAR T cell cytotoxicity but was not required for in vitro or in vivo leukemia clearance. Upon CAR-mediated in vitro activation, perforin-deficient CAR T cells produced higher amounts of proinflammatory cytokines compared with WT CAR T cells. Following in vivo clearance of leukemia, perforin-deficient CAR T cells reexpanded, resulting in splenomegaly with disruption of normal splenic architecture and the presence of hemophagocytes, which are findings reminiscent of HLH. Notably, a substantial fraction of patients who received anti-CD22 CAR T cells also experienced biphasic inflammation, with the second phase occurring after the resolution of cytokine release syndrome, resembling clinical manifestations of HLH. Elevated inflammatory cytokines such as IL-1[beta] and IL-18 and concurrent late CAR T cell expansion characterized the HLH-like syndromes occurring in the murine model and in humans. Thus, a murine model of perforin-deficient CAR T cells recapitulated late-onset inflammatory toxicities occurring in human CAR T cell recipients, providing therapeutically relevant mechanistic insights., Introduction Chimeric antigen receptor T cells (CAR T cells) are highly effective against B cell malignancies (1-8) but are frequently associated with cytokine-mediated toxicities or hyperinflammatory conditions (9, 10). The [...]

Published
2020
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18. Ancient familial Mediterranean fever mutations in human pyrin and resistance to Yersinia pestis

Author

Park, Yong Hwan, Remmers, Elaine F., Lee, Wonyong, Ombrello, Amanda K., Chung, Lawton K., Shilei, Zhao, Stone, Deborah L., Ivanov, Maya I., Loeven, Nicole A., Barron, Karyl S., Hoffmann, Patrycja, Nehrebecky, Michele, Akkaya-Ulum, Yeliz Z., Sag, Erdal, Balci-Peynircioglu, Banu, Aksentijevich, Ivona, Gül, Ahmet, Rotimi, Charles N., Chen, Hua, Bliska, James B., Ozen, Seza, Kastner, Daniel L., Shriner, Daniel, and Chae, Jae Jin

Published
2020
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20. Autoinflammatory Diseases

Author

Naik, Haley B., Ombrello, Amanda K., Cowen, Edward W., Gaspari, Anthony A., editor, Tyring, Stephen K., editor, and Kaplan, Daniel H., editor

Published
2017
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22. AA Amyloidosis

Author

Ombrello, Amanda K., Aksentijevich, Ivona, Giordano, Antonio, Series editor, Picken, Maria M., editor, Herrera, Guillermo A., editor, and Dogan, Ahmet, editor

Published
2015
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23. Warts and DADA2: a Mere Coincidence?

Author

Arts, Katrijn, Bergerson, Jenna R. E., Ombrello, Amanda K., Similuk, Morgan, Oler, Andrew J., Agharahimi, Anahita, Mace, Emily M., Hershfield, Mike, Wouters, Carine, De Somer, Lien, Morren, Marie-Anne, Diego, Rebeca Perez-de, Moens, Leen, Freeman, Alexandra F., and Meyts, Isabelle

Published
2018
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25. Evaluation and Management of Deficiency of Adenosine Deaminase 2: An International Consensus Statement

Author

Research UMC Utrecht, Cluster B, Immuno/reuma patientenzorg, Child Health, Infection & Immunity, Lee, Pui Y., Davidson, Brad A., Abraham, Roshini S., Alter, Blanche, Arostegui, Juan I., Bell, Katherine, Belot, Alexandre, Bergerson, Jenna R.E., Bernard, Timothy J., Brogan, Paul A., Berkun, Yackov, Deuitch, Natalie T., Dimitrova, Dimana, Georgin-Lavialle, Sophie A., Gattorno, Marco, Grimbacher, Bodo, Hashem, Hasan, Hershfield, Michael S., Ichord, Rebecca N., Izawa, Kazushi, Kanakry, Jennifer A., Khubchandani, Raju P., Klouwer, Femke C.C., Luton, Evan A., Man, Ada W., Meyts, Isabelle, Van Montfrans, Joris M., Ozen, Seza, Saarela, Janna, Santo, Gustavo C., Sharma, Aman, Soldatos, Ariane, Sparks, Rachel, Torgerson, Troy R., Uriarte, Ignacio Leandro, Youngstein, Taryn A.B., Zhou, Qing, Aksentijevich, Ivona, Kastner, Daniel L., Chambers, Eugene P., Ombrello, Amanda K., Research UMC Utrecht, Cluster B, Immuno/reuma patientenzorg, Child Health, Infection & Immunity, Lee, Pui Y., Davidson, Brad A., Abraham, Roshini S., Alter, Blanche, Arostegui, Juan I., Bell, Katherine, Belot, Alexandre, Bergerson, Jenna R.E., Bernard, Timothy J., Brogan, Paul A., Berkun, Yackov, Deuitch, Natalie T., Dimitrova, Dimana, Georgin-Lavialle, Sophie A., Gattorno, Marco, Grimbacher, Bodo, Hashem, Hasan, Hershfield, Michael S., Ichord, Rebecca N., Izawa, Kazushi, Kanakry, Jennifer A., Khubchandani, Raju P., Klouwer, Femke C.C., Luton, Evan A., Man, Ada W., Meyts, Isabelle, Van Montfrans, Joris M., Ozen, Seza, Saarela, Janna, Santo, Gustavo C., Sharma, Aman, Soldatos, Ariane, Sparks, Rachel, Torgerson, Troy R., Uriarte, Ignacio Leandro, Youngstein, Taryn A.B., Zhou, Qing, Aksentijevich, Ivona, Kastner, Daniel L., Chambers, Eugene P., and Ombrello, Amanda K.

Published
2023

26. Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease

Author

Zhou, Qing, Yu, Xiaomin, Demirkaya, Erkan, Deuitch, Natalie, Stone, Deborah, Tsai, Wanxia Li, Kuehn, Hye Sun, Wang, Hongying, Yang, Dan, Park, Yong Hwan, Ombrello, Amanda K., Blake, Mary, Romeo, Tina, Remmers, Elaine F., Chae, Jae Jin, Mullikin, James C., Güzel, Ferhat, Milner, Joshua D., Boehm, Manfred, Rosenzweig, Sergio D., Gadina, Massimo, Welch, Steven B., Özen, Seza, Topaloglu, Rezan, Abinun, Mario, Kastner, Daniel L., and Aksentijevich, Ivona

Published
2016

28. Evaluation and Management of Deficiency of Adenosine Deaminase 2: An International Consensus Statement

Author

Lee, Pui Y, Davidson, Brad A, Abraham, Roshini S, Alter, Blanche, Arostegui, Juan I, Bell, Katherine, Belot, Alexandre, Bergerson, Jenna RE, Bernard, Timothy J, Brogan, Paul A, Berkun, Yackov, Deuitch, Natalie T, Dimitrova, Dimana, Georgin-Lavialle, Sophie A, Gattorno, Marco, Grimbacher, Bodo, Hashem, Hasan, Hershfield, Michael S, Ichord, Rebecca N, Izawa, Kazushi, Kanakry, Jennifer A, Khubchandani, Raju P, Klouwer, Femke CC, Luton, Evan A, Man, Ada W, Meyts, Isabelle, Van Montfrans, Joris M, Ozen, Seza, Saarela, Janna, Santo, Gustavo C, Sharma, Aman, Soldatos, Ariane, Sparks, Rachel, Torgerson, Troy R, Uriarte, Ignacio Leandro, Youngstein, Taryn AB, Zhou, Qing, Aksentijevich, Ivona, Kastner, Daniel L, Chambers, Eugene P, Ombrello, Amanda K, and DADA2 Foundation

Subjects
Heterozygote, Phenotype, Adenosine Deaminase, Intercellular Signaling Peptides and Proteins
Abstract

IMPORTANCE: Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited disease characterized by systemic vasculitis, early-onset stroke, bone marrow failure, and/or immunodeficiency affecting both children and adults. DADA2 is among the more common monogenic autoinflammatory diseases, with an estimate of more than 35 000 cases worldwide, but currently, there are no guidelines for diagnostic evaluation or management. OBJECTIVE: To review the available evidence and develop multidisciplinary consensus statements for the evaluation and management of DADA2. EVIDENCE REVIEW: The DADA2 Consensus Committee developed research questions based on data collected from the International Meetings on DADA2 organized by the DADA2 Foundation in 2016, 2018, and 2020. A comprehensive literature review was performed for articles published prior to 2022. Thirty-two consensus statements were generated using a modified Delphi process, and evidence was graded using the Oxford Center for Evidence-Based Medicine Levels of Evidence. FINDINGS: The DADA2 Consensus Committee, comprising 3 patient representatives and 35 international experts from 18 countries, developed consensus statements for (1) diagnostic testing, (2) screening, (3) clinical and laboratory evaluation, and (4) management of DADA2 based on disease phenotype. Additional consensus statements related to the evaluation and treatment of individuals with DADA2 who are presymptomatic and carriers were generated. Areas with insufficient evidence were identified, and questions for future research were outlined. CONCLUSIONS AND RELEVANCE: DADA2 is a potentially fatal disease that requires early diagnosis and treatment. By summarizing key evidence and expert opinions, these consensus statements provide a framework to facilitate diagnostic evaluation and management of DADA2. ispartof: JAMA Netw Open vol:6 issue:5 pages:e2315894- ispartof: location:United States status: Published online

Published
2023

29. Biallelic human SHARPINloss of function induces autoinflammation and immunodeficiency

Author

Oda, Hirotsugu, Manthiram, Kalpana, Chavan, Pallavi Pimpale, Rieser, Eva, Veli, Önay, Kaya, Öykü, Rauch, Charles, Nakabo, Shuichiro, Kuehn, Hye Sun, Swart, Mariël, Wang, Yanli, Çelik, Nisa Ilgim, Molitor, Anne, Ziaee, Vahid, Movahedi, Nasim, Shahrooei, Mohammad, Parvaneh, Nima, Alipour-olyei, Nasrin, Carapito, Raphael, Xu, Qin, Preite, Silvia, Beck, David B., Chae, Jae Jin, Nehrebecky, Michele, Ombrello, Amanda K., Hoffmann, Patrycja, Romeo, Tina, Deuitch, Natalie T., Matthíasardóttir, Brynja, Mullikin, James, Komarow, Hirsh, Stoddard, Jennifer, Niemela, Julie, Dobbs, Kerry, Sweeney, Colin L., Anderton, Holly, Lawlor, Kate E., Yoshitomi, Hiroyuki, Yang, Dan, Boehm, Manfred, Davis, Jeremy, Mudd, Pamela, Randazzo, Davide, Tsai, Wanxia Li, Gadina, Massimo, Kaplan, Mariana J., Toguchida, Junya, Mayer, Christian T., Rosenzweig, Sergio D., Notarangelo, Luigi D., Iwai, Kazuhiro, Silke, John, Schwartzberg, Pamela L., Boisson, Bertrand, Casanova, Jean-Laurent, Bahram, Seiamak, Rao, Anand Prahalad, Peltzer, Nieves, Walczak, Henning, Lalaoui, Najoua, Aksentijevich, Ivona, and Kastner, Daniel L.

Abstract

The linear ubiquitin assembly complex (LUBAC) consists of HOIP, HOIL-1 and SHARPIN and is essential for proper immune responses. Individuals with HOIP and HOIL-1 deficiencies present with severe immunodeficiency, autoinflammation and glycogen storage disease. In mice, the loss of Sharpinleads to severe dermatitis due to excessive keratinocyte cell death. Here, we report two individuals with SHARPIN deficiency who manifest autoinflammatory symptoms but unexpectedly no dermatological problems. Fibroblasts and B cells from these individuals showed attenuated canonical NF-κB responses and a propensity for cell death mediated by TNF superfamily members. Both SHARPIN-deficient and HOIP-deficient individuals showed a substantial reduction of secondary lymphoid germinal center B cell development. Treatment of one SHARPIN-deficient individual with anti-TNF therapies led to complete clinical and transcriptomic resolution of autoinflammation. These findings underscore the critical function of the LUBAC as a gatekeeper for cell death-mediated immune dysregulation in humans.

Published
2024
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30. Humoral Reconstitution after Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients Pretreated with Targeted Anti-CD20 Therapy

Author

Dimitrova, Dimana, primary, Sponaugle, Jennifer, additional, Uzel, Gulbu, additional, Notarangelo, Luigi D., additional, Freeman, Alexandra F., additional, Bergerson, Jenna R.E., additional, Malech, Harry L., additional, Holland, Steven M., additional, Roschewski, Mark, additional, Melani, Christopher, additional, Cohen, Jeffrey I., additional, Lisco, Andrea, additional, Sereti, Irini, additional, Zerbe, Christa S., additional, Ombrello, Amanda K., additional, Stone, Deborah, additional, Cuellar-Rodriguez, Jennifer, additional, Gea-Banacloche, Juan, additional, Wilder, Jennifer, additional, Chai, Amy, additional, Kanakry, Christopher G., additional, and Kanakry, Jennifer A., additional

Published
2023
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32. AA Amyloidosis

Author

Ombrello, Amanda K., Aksentijevich, Ivona, Picken MD, PhD, FASN, Maria M., editor, Dogan, M.D., Ph.D., Ahmet, editor, and Herrera, M.D., Guillermo A., editor

Published
2012
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33. Human LUBAC deficiency leads to autoinflammation and immunodeficiency by dysregulation in TNF-mediated cell death

Author

Oda, Hirotsugu, primary, Manthiram, Kalpana, additional, Chavan, Pallavi Pimpale, additional, Nakabo, Shuichiro, additional, Kuehn, Hye Sun, additional, Beck, David B., additional, Chae, Jae Jin, additional, Nehrebecky, Michele, additional, Ombrello, Amanda K., additional, Romeo, Tina, additional, Deuitch, Natalie, additional, Matthíasardóttir, Brynja, additional, Mullikin, Jim, additional, Stoddard, Jennifer, additional, Niemela, Julie, additional, Anderton, Holly, additional, Lawlor, Kate E., additional, Yoshitomi, Hiroyuki, additional, Yang, Dan, additional, Boehm, Manfred, additional, Davis, Jeremy, additional, Mudd, Pamela, additional, Randazzo, Davide, additional, Tsai, Wanxia Li, additional, Gadina, Massimo, additional, Kaplan, Mariana J., additional, Toguchida, Junya, additional, Mayer, Christian, additional, Rosenzweig, Sergio D., additional, Iwai, Kazuhiro, additional, Silke, John, additional, Boisson, Bertrand, additional, Casanova, Jean-Laurent, additional, Rao, Anand, additional, Lalaoui, Najoua, additional, Aksentijevich, Ivona, additional, and Kastner, Daniel L., additional

Published
2022
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35. Gain-of-function mutations inALPK1cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome

Author

Kozycki, Christina Torres, primary, Kodati, Shilpa, additional, Huryn, Laryssa, additional, Wang, Hongying, additional, Warner, Blake M, additional, Jani, Priyam, additional, Hammoud, Dima, additional, Abu-Asab, Mones S, additional, Jittayasothorn, Yingyos, additional, Mattapallil, Mary J, additional, Tsai, Wanxia Li, additional, Ullah, Ehsan, additional, Zhou, Ping, additional, Tian, Xiaoying, additional, Soldatos, Ariane, additional, Moutsopoulos, Niki, additional, Kao-Hsieh, Marie, additional, Heller, Theo, additional, Cowen, Edward W, additional, Lee, Chyi-Chia Richard, additional, Toro, Camilo, additional, Kalsi, Shelley, additional, Khavandgar, Zohreh, additional, Baer, Alan, additional, Beach, Margaret, additional, Long Priel, Debra, additional, Nehrebecky, Michele, additional, Rosenzweig, Sofia, additional, Romeo, Tina, additional, Deuitch, Natalie, additional, Brenchley, Laurie, additional, Pelayo, Eileen, additional, Zein, Wadih, additional, Sen, Nida, additional, Yang, Alexander H, additional, Farley, Gary, additional, Sweetser, David A, additional, Briere, Lauren, additional, Yang, Janine, additional, de Oliveira Poswar, Fabiano, additional, Schwartz, Ida Vanessa D, additional, Silva Alves, Tamires, additional, Dusser, Perrine, additional, Koné-Paut, Isabelle, additional, Touitou, Isabelle, additional, Titah, Salah Mohamed, additional, van Hagen, Petrus Martin, additional, van Wijck, Rogier T A, additional, van der Spek, Peter J, additional, Yano, Hiromi, additional, Benneche, Andreas, additional, Apalset, Ellen M, additional, Jansson, Ragnhild Wivestad, additional, Caspi, Rachel R, additional, Kuhns, Douglas Byron, additional, Gadina, Massimo, additional, Takada, Hidetoshi, additional, Ida, Hiroaki, additional, Nishikomori, Ryuta, additional, Verrecchia, Elena, additional, Sangiorgi, Eugenio, additional, Manna, Raffaele, additional, Brooks, Brian P, additional, Sobrin, Lucia, additional, Hufnagel, Robert B, additional, Beck, David, additional, Shao, Feng, additional, Ombrello, Amanda K, additional, Aksentijevich, Ivona, additional, and Kastner, Daniel L, additional

Published
2022
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36. Anakinra utilization in refractory pediatric CAR T-cell associated toxicities

Author

Diorio, Caroline, primary, Vatsayan, Anant, additional, Talleur, Aimee C., additional, Annesley, Colleen, additional, Jaroscak, Jennifer J., additional, Shalabi, Haneen, additional, Ombrello, Amanda K., additional, Hudspeth, Michelle, additional, Maude, Shannon L., additional, Gardner, Rebecca A., additional, and Shah, Nirali N., additional

Published
2022
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37. Brief Report: Deficiency of Complement 1r Subcomponent in Early‐Onset Systemic Lupus Erythematosus: The Role of Disease‐Modifying Alleles in a Monogenic Disease

Author

Demirkaya, Erkan, Zhou, Qing, Smith, Carolyne K., Ombrello, Michael J., Deuitch, Natalie, Tsai, Wanxia L., Hoffmann, Patrycja, Remmers, Elaine F., Takeuchi, Masaki, Park, Yong Hwan, Chae, JaeJin, Barut, Kenan, Simsek, Dogan, Adrovic, Amra, Sahin, Sezgin, Caliskan, Salim, Chandrasekharappa, Settara C., Hasni, Sarfaraz A., Ombrello, Amanda K., Gadina, Massimo, Kastner, Daniel L., Kaplan, Mariana J., Kasapcopur, Ozgur, and Aksentijevich, Ivona

Published
2017
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38. 16 - Prospective Clinical Trial of Mycophenolate Mofetil (MMF) De-Escalation in Allogeneic Hematopoietic Cell Transplantation (HCT) for Primary Immunodeficiency (PID): MMF Is Dispensable in Reduced-Intensity Conditioning, Posttransplantation Cyclophosphamide(PTCy)-Based HCT

Author

Dimitrova, Dimana, Napier, Scott, Sponaugle, Jennifer, Stokes, Anita, Hyder, Mustafa, Uzel, Gulbu, Notarangelo, Luigi D., Freeman, Alexandra F., Bergerson, Jenna R.E., Holland, Steven M., Roschewski, Mark, Melani, Christopher, Cohen, Jeffrey I., Lisco, Andrea, Sereti, Irini, Zerbe, Christa, Ombrello, Amanda K., Stone, Deborah, Cuellar-Rodriguez, Jennifer, Gea-Banacloche, Juan, Parta, Mark, Wilder, Jennifer, Chai, Amy, Fowler, Daniel H., Gress, Ronald E, Kanakry, Christopher G., and Kanakry, Jennifer A.

Published
2022
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39. TNF inhibition in vasculitis management in adenosine deaminase 2 deficiency (DADA2)

Author

Deuitch, Natalie T., primary, Yang, Dan, additional, Lee, Pui Y., additional, Yu, Xiaomin, additional, Moura, Natalia Sampaio, additional, Schnappauf, Oskar, additional, Ombrello, Amanda K., additional, Stone, Deborah, additional, Kuehn, Hye Sun, additional, Rosenzweig, Sergio D., additional, Hoffmann, Patrycja, additional, Cudrici, Cornelia, additional, Levy, Deborah M., additional, Kessler, Elizabeth, additional, Soep, Jennifer B., additional, Hay, Arielle D., additional, Dalrymple, Austin, additional, Zhang, Yu, additional, Sun, Li, additional, Zhang, Qiuye, additional, Tang, Xuemei, additional, Wu, Yuan, additional, Rao, Koneti, additional, Li, Haibo, additional, Luo, Hong, additional, Zhang, Yao, additional, Burnham, Jon M., additional, Boehm, Manfred, additional, Barron, Karyl, additional, Kastner, Daniel L., additional, Aksentijevich, Ivona, additional, and Zhou, Qing, additional

Published
2022
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40. Prospective Clinical Trial of Mycophenolate Mofetil (MMF) De-Escalation in Allogeneic Hematopoietic Cell Transplantation (HCT) for Primary Immunodeficiency (PID): MMF Is Dispensable in Reduced-Intensity Conditioning, Posttransplantation Cyclophosphamide(PTCy)-Based HCT

Author

Dimitrova, Dimana, primary, Napier, Scott, additional, Sponaugle, Jennifer, additional, Stokes, Anita, additional, Hyder, Mustafa, additional, Uzel, Gulbu, additional, Notarangelo, Luigi D., additional, Freeman, Alexandra F., additional, Bergerson, Jenna R.E., additional, Holland, Steven M., additional, Roschewski, Mark, additional, Melani, Christopher, additional, Cohen, Jeffrey I., additional, Lisco, Andrea, additional, Sereti, Irini, additional, Zerbe, Christa, additional, Ombrello, Amanda K., additional, Stone, Deborah, additional, Cuellar-Rodriguez, Jennifer, additional, Gea-Banacloche, Juan, additional, Parta, Mark, additional, Wilder, Jennifer, additional, Chai, Amy, additional, Fowler, Daniel H., additional, Gress, Ronald E, additional, Kanakry, Christopher G., additional, and Kanakry, Jennifer A., additional

Published
2022
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41. Sars-Cov-2 Infection and Vaccination in Recipients of Reduced-Intensity Conditioning, Posttransplantation Cyclophosphamide (PTCy)-Based Allogeneic Hematopoietic Cell Transplantation (HCT)

Author

Dimitrova, Dimana, primary, Sponaugle, Jennifer, additional, Bergerson, Jenna R.E., additional, Cohen, Jeffrey I., additional, Freeman, Alexandra F., additional, Notarangelo, Luigi D., additional, Uzel, Gulbu, additional, Lisco, Andrea, additional, Sereti, Irini, additional, Ombrello, Amanda K., additional, Uriarte, Ignacio, additional, Campos, Jessenia, additional, Chai, Amy, additional, Flomerfelt, Francis, additional, and Kanakry, Jennifer A., additional

Published
2022
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42. The Spectrum of the Deficiency of Adenosine Deaminase 2: An Observational Analysis of a 60 Patient Cohort

Author

Barron, Karyl S., primary, Aksentijevich, Ivona, additional, Deuitch, Natalie T., additional, Stone, Deborah L., additional, Hoffmann, Patrycja, additional, Videgar-Laird, Ryan, additional, Soldatos, Ariane, additional, Bergerson, Jenna, additional, Toro, Camilo, additional, Cudrici, Cornelia, additional, Nehrebecky, Michele, additional, Romeo, Tina, additional, Jones, Anne, additional, Boehm, Manfred, additional, Kanakry, Jennifer A., additional, Dimitrova, Dimana, additional, Calvo, Katherine R., additional, Alao, Hawwa, additional, Kapuria, Devika, additional, Ben-Yakov, Gil, additional, Pichard, Dominique C., additional, Hathaway, Londa, additional, Brofferio, Alessandra, additional, McRae, Elisa, additional, Moura, Natalia Sampaio, additional, Schnappauf, Oskar, additional, Rosenzweig, Sofia, additional, Heller, Theo, additional, Cowen, Edward W., additional, Kastner, Daniel L., additional, and Ombrello, Amanda K., additional

Published
2022
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43. Characterization of HLH-like manifestations as a CRS variant in patients receiving CD22 CAR T cells

Author

Lichtenstein, Daniel A., primary, Schischlik, Fiorella, additional, Shao, Lipei, additional, Steinberg, Seth M., additional, Yates, Bonnie, additional, Wang, Hao-Wei, additional, Wang, Yanyu, additional, Inglefield, Jon, additional, Dulau-Florea, Alina, additional, Ceppi, Francesco, additional, Hermida, Leandro C., additional, Stringaris, Kate, additional, Dunham, Kim, additional, Homan, Philip, additional, Jailwala, Parthav, additional, Mirazee, Justin, additional, Robinson, Welles, additional, Chisholm, Karen M., additional, Yuan, Constance, additional, Stetler-Stevenson, Maryalice, additional, Ombrello, Amanda K., additional, Jin, Jianjian, additional, Fry, Terry J., additional, Taylor, Naomi, additional, Highfill, Steven L., additional, Jin, Ping, additional, Gardner, Rebecca A., additional, Shalabi, Haneen, additional, Ruppin, Eytan, additional, Stroncek, David F., additional, and Shah, Nirali N., additional

Published
2021
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45. Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS

Author

Ferrada, Marcela A., primary, Sikora, Keith A., additional, Luo, Yiming, additional, Wells, Kristina V., additional, Patel, Bhavisha, additional, Groarke, Emma M., additional, Ospina Cardona, Daniela, additional, Rominger, Emily, additional, Hoffmann, Patrycja, additional, Le, Mimi T., additional, Deng, Zuoming, additional, Quinn, Kaitlin A., additional, Rose, Emily, additional, Tsai, Wanxia L., additional, Wigerblad, Gustaf, additional, Goodspeed, Wendy, additional, Jones, Anne, additional, Wilson, Lorena, additional, Schnappauf, Oskar, additional, Laird, Ryan S., additional, Kim, Jeff, additional, Allen, Clint, additional, Sirajuddin, Arlene, additional, Chen, Marcus, additional, Gadina, Massimo, additional, Calvo, Katherine R., additional, Kaplan, Mariana J., additional, Colbert, Robert A., additional, Aksentijevich, Ivona, additional, Young, Neal S., additional, Savic, Sinisa, additional, Kastner, Daniel L., additional, Ombrello, Amanda K., additional, Beck, David B., additional, and Grayson, Peter C., additional

Published
2021
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46. Consequences of hemophagocytic lymphohistiocytosis‐like cytokine release syndrome toxicities and concurrent bacteremia

Author

Masih, Katherine E., primary, Ligon, John A., additional, Yates, Bonnie, additional, Shalabi, Haneen, additional, Little, Lauren, additional, Islam, Zahin, additional, Ombrello, Amanda K., additional, Inglefield, Jon, additional, Nussenblatt, Veronique, additional, Manion, Maura, additional, Khan, Javed, additional, and Shah, Nirali N., additional

Published
2021
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47. Early-Onset Stroke and Vasculopathy Associated with Mutations in ADA2

Author

Zhou, Qing, Yang, Dan, Ombrello, Amanda K., Zavialov, Andrey V., Toro, Camilo, Zavialov, Anton V., Stone, Deborah L., Chae, Jae Jin, Rosenzweig, Sergio D., Bishop, Kevin, Barron, Karyl S., Kuehn, Hye Sun, Hoffmann, Patrycja, Negro, Alejandra, Tsai, Wanxia L., Cowen, Edward W., Pei, Wuhong, Milner, Joshua D., Silvin, Christopher, Heller, Theo, Chin, David T., Patronas, Nicholas J., Barber, John S., Lee, Chyi-Chia R., Wood, Geryl M., Ling, Alexander, Kelly, Susan J., Kleiner, David E., Mullikin, James C., Ganson, Nancy J., Kong, Heidi H., Hambleton, Sophie, Candotti, Fabio, Quezado, Martha M., Calvo, Katherine R., Alao, Hawwa, Barham, Beverly K., Jones, Anne, Meschia, James F., Worrall, Bradford B., Kasner, Scott E., Rich, Stephen S., Goldbach-Mansky, Raphaela, Abinun, Mario, Chalom, Elizabeth, Gotte, Alisa C., Punaro, Marilynn, Pascual, Virginia, Verbsky, James W., Torgerson, Troy R., Singer, Nora G., Gershon, Timothy R., Ozen, Seza, Karadag, Omer, Fleisher, Thomas A., Remmers, Elaine F., Burgess, Shawn M., Moir, Susan L., Gadina, Massimo, Sood, Raman, Hershfield, Michael S., Boehm, Manfred, Kastner, Daniel L., and Aksentijevich, Ivona

Published
2014
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49. Analysis of deficiency of adenosine deaminase 2 pathogenesis based on single-cell RNA sequencing of monocytes

Author

Watanabe, Naoki, primary, Gao, Shouguo, additional, Wu, Zhijie, additional, Batchu, Sai, additional, Kajigaya, Sachiko, additional, Diamond, Carrie, additional, Alemu, Lemlem, additional, Raffo, Diego Quinones, additional, Hoffmann, Patrycja, additional, Stone, Deborah, additional, Ombrello, Amanda K, additional, and Young, Neal S, additional

Published
2021
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50. Distal Equine Anti-Thymocyte Globulin (ATG) As an Adjunct to Reduced Intensity Conditioning and Posttransplantation Cyclophosphamide (PTCy) for Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients with Benign and Malignant Disorders of T Cell Proliferation or Dysregulation

Author

Dimitrova, Dimana, primary, Napier, Scott, additional, Stokes, Anita, additional, Uzel, Gulbu, additional, Miljkovic, Milos, additional, Pittaluga, Stefania, additional, Wang, Hao-Wei, additional, Notarangelo, Luigi D., additional, Ombrello, Amanda K., additional, Stone, Deborah, additional, Cuellar-Rodriguez, Jennifer, additional, Wilder, Jennifer, additional, Hicks, Stephanie N., additional, Sadler, Jennifer L., additional, Fowler, Daniel H., additional, Gress, Ronald E, additional, Kanakry, Chris G., additional, and Kanakry, Jennifer A., additional

Published
2021
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