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54. WED-152 Design and study population of MITIGATE: the first multinational randomized controlled clinical trial in IgG4 related disease, evaluating the efficacy and safety of the CD19 B cell depleting agent inebilizumab

Author

Stone, John, primary, Culver, Emma, additional, Khosroshahi, Arezou, additional, Zhang, Wen, additional, Torre, Emanuel Della, additional, Okazaki, Kazuichi, additional, Tanaka, Yoshiya, additional, Lohr, Matthias, additional, Schleinitz, Nicolas, additional, Dong, Lingli, additional, Umehara, Hisanori, additional, Lanzillotta, Marco, additional, Wallace, Zachary, additional, Ebbo, Mikael, additional, Webster, George, additional, Wu, Yanping, additional, Cimbora, Daniel, additional, and Rampal, Nishi, additional

Published
2024
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55. The tank debate

Author

Stone, John

Subjects
BOOK REVIEWS
Published
2001

56. Evaluation of the safety, efficacy, and mechanism of action of obexelimab for the treatment of patients with IgG4-related disease: an open-label, single-arm, single centre, phase 2 pilot trial

Author

Perugino, Cory A, Wallace, Zachary S, Zack, Debra J, Quinn, Shauna M, Poma, Allen, Fernandes, Ana D, Foster, Paul, DeMattos, Steve, Burington, Bart, Liu, Hang, Allard-Chamard, Hugues, Smith, Nathan, Kai, Xin, Xing, Kelly, Pillai, Shiv, and Stone, John H

Published
2023
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59. Extrafollicular IgD−CD27−CXCR5−CD11c− DN3 B cells infiltrate inflamed tissues in autoimmune fibrosis and in severe COVID-19

Author

Allard-Chamard, Hugues, Kaneko, Naoki, Bertocchi, Alice, Sun, Na, Boucau, Julie, Kuo, Hsiao-Hsuan, Farmer, Jocelyn R., Perugino, Cory, Mahajan, Vinay S., Murphy, Samuel J.H., Premo, Katherine, Diefenbach, Thomas, Ghebremichael, Musie, Yuen, Grace, Kotta, Alekhya, Akman, Zafer, Lichterfeld, Mathias, Walker, Bruce D., Yu, Xu G., Moriyama, Masafumi, Maehara, Takashi, Nakamura, Seiji, Stone, John H., Padera, Robert F., and Pillai, Shiv

Published
2023
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76. The pediatric glucocorticoid toxicity index

Author

Brogan, Paul, Naden, Ray, Ardoin, Stacy P., Cooper, Jennifer C., De Benedetti, Fabrizio, Dicaire, Jean-Francois, Eleftheriou, Despina, Feldman, Brian, Goldin, Jon, Karol, Seth E., Price-Kuehne, Fiona, Skuse, David, Stratakis, Constantine A., Webb, Nicholas, and Stone, John H.

Published
2022
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78. IgG4‐related disease: Association with a rare gene variant expressed in cytotoxic T cells

Author

Newman, John H, Shaver, Aaron, Sheehan, Jonathan H, Mallal, Simon, Stone, John H, Pillai, Shiv, Bastarache, Lisa, Riebau, Derek, Allard‐Chamard, Hugues, Stone, William M, Perugino, Cory, Pilkinton, Mark, Smith, Scott A, McDonnell, Wyatt J, Capra, John A, Meiler, Jens, Cogan, Joy, Xing, Kelly, Mahajan, Vinay S, Mattoo, Hamid, Hamid, Rizwan, Phillips, John A, Adams, David R, Aday, Aaron, Alejandro, Mercedes E, Allard, Patrick, Ashley, Euan A, Azamian, Mahshid S, Bacino, Carlos A, Balasubramanyam, Ashok, Barseghyan, Hayk, Batzli, Gabriel F, Beggs, Alan H, Behnam, Babak, Bellen, Hugo J, Bernstein, Jonathan A, Bican, Anna, Bick, David P, Birch, Camille L, Bonner, Devon, Boone, Braden E, Bostwick, Bret L, Briere, Lauren C, Brown, Donna M, Brush, Matthew, Burke, Elizabeth A, Burrage, Lindsay C, Butte, Manish J, Chen, Shan, Clark, Gary D, Coakley, Terra R, Cooper, Cynthia M, Cope, Heidi, Craigen, William J, D'Souza, Precilla, Davids, Mariska, Davidson, Jean M, Dayal, Jyoti G, Dell'Angelica, Esteban C, Dhar, Shweta U, Dipple, Katrina M, Donnell‐Fink, Laurel A, Dorrani, Naghmeh, Dorset, Daniel C, Douine, Emilie D, Draper, David D, Dries, Annika M, Eckstein, David J, Emrick, Lisa T, Eng, Christine M, Enns, Gregory M, Eskin, Ascia, Esteves, Cecilia, Estwick, Tyra, Fernandez, Liliana, Ferreira, Carlos, Fisher, Paul G, Fogel, Brent L, Friedman, Noah D, Gahl, William A, Glanton, Emily, Godfrey, Rena A, Goldman, Alica M, Goldstein, David B, Gould, Sarah E, Gourdine, Jean‐Philippe F, Groden, Catherine A, Gropman, Andrea L, Haendel, Melissa, Hanchard, Neil A, Handley, Lori H, Herzog, Matthew R, High, Francis, Holm, Ingrid A, Hom, Jason, Howerton, Ellen M, Huang, Yong, Jamal, Fariha, Jiang, Yong‐hui, and Johnston, Jean M

Subjects
Biological Sciences, Genetics, Rare Diseases, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Adolescent, CD4-Positive T-Lymphocytes, Genetic Variation, Humans, Immunoglobulin G, Immunoglobulin G4-Related Disease, Male, Middle Aged, T-Lymphocytes, Cytotoxic, cytotoxic lymphocytes, heritable, IgG4-RD, Undiagnosed Disease Network, Medicinal and Biomolecular Chemistry, Clinical Sciences, Medicinal and biomolecular chemistry
Abstract

BackgroundFamily screening of a 48-year-old male with recently diagnosed IgG4-related disease (IgG4-RD) revealed unanticipated elevations in plasma IgG4 in his two healthy teenaged sons.MethodsWe performed gene sequencing, immune cell studies, HLA typing, and analyses of circulating cytotoxic CD4+ T lymphocytes and plasmablasts to seek clues to pathogenesis. DNA from a separate cohort of 99 patients with known IgG4-RD was also sequenced for the presence of genetic variants in a specific gene, FGFBP2.ResultsThe three share a previously unreported heterozygous single base deletion in fibroblast growth factor binding protein type 2 (FGFBP2), which causes a frameshift in the coding sequence. The FGFBP2 protein is secreted by cytotoxic T-lymphocytes and binds fibroblast growth factor. The variant sequence in the FGFBP2 protein is predicted to form a disordered random coil rather than a helical-turn-helix structure, unable to adopt a stable conformation. The proband and the two sons had 5-10-fold higher numbers of circulating cytotoxic CD4 + T cells and plasmablasts compared to matched controls. The three members also share a homozygous missense common variant in FGFBP2 found in heterozygous form in ~40% of the population. This common variant was found in 73% of an independent, well characterized IgG4-RD cohort, showing enrichment in idiopathic IgG4-RD.ConclusionsThe presence of a shared deleterious variant and homozygous common variant in FGFBP2 in the proband and sons strongly implicates this cytotoxic T cell product in the pathophysiology of IgG4-RD. The high prevalence of a common FGFBP2 variant in sporadic IgG4-RD supports the likelihood of participation in disease.

Published
2019

82. Structure and Composition of Pluto's atmosphere from the New Horizons Solar Ultraviolet Occultation

Author

Young, Leslie A., Kammer, Joshua A., Steffl, Andrew J., Gladstone, G. Randall, Summers, Michael E., Strobel, Darrell F., Hinson, David P., Stern, S. Alan, Weaver, Harold A., Olkin, Catherine B., Ennico, Kimberly, McComas, David J., Cheng, Andrew F., Gao, Peter, Lavvas, Panayotis, Linscott, Ivan R., Wong, Michael L., Yung, Yuk L., Cunningham, Nathanial, Davis, Michael, Parker, Joel Wm., Schindhelm, Rebecca, Siegmund, Oswald H. W., Stone, John, Retherford, Kurt, and Versteeg, Maarten

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

The Alice instrument on NASA's New Horizons spacecraft observed an ultraviolet solar occultation by Pluto's atmosphere on 2015 July 14. The transmission vs. altitude was sensitive to the presence of N2, CH4, C2H2, C2H4, C2H6, and haze. We derived line-of-sight abundances and local number densities for the 5 molecular species, and line-of-sight optical depth and extinction coefficients for the haze. We found the following major conclusions: 1) We confirmed temperatures in Pluto's upper atmosphere that were colder than expected before the New Horizons flyby, with upper atmospheric temperatures near 65-68 K. The inferred enhanced Jeans escape rates were (3e22-7e22) N2/s and (4e25-8e25) CH4/s at the exobase (at a radius of ~2900 km, or an altitude of ~1710 km). 2) We measured CH4 abundances from 80 to 1200 km above the surface. A joint analysis of the Alice CH4 and Alice and REX N2 measurements implied a very stable lower atmosphere with a small eddy diffusion coefficient, most likely between 550 and 4000 cm2/s. Such a small eddy diffusion coefficient placed the homopause within 12 km of the surface, giving Pluto a small planetary boundary layer. The inferred CH4 surface mixing ratio was ~0.28-0.35%. 3) The abundance profiles of the C2Hx hydrocarbons (C2H2, C2H4, C2H6) were not simply exponential with altitude. We detected local maxima in line-of-sight abundance near 410 km altitude for C2H4, near 320 km for C2H2, and an inflection point or the suggestion of a local maximum at 260 km for C2H6. We also detected local minima near 200 km altitude for C2H4, near 170 km for C2H2, and an inflection point or minimum near 170-200 km for C2H6. These compared favorably with models for hydrocarbon production near 300-400 km and haze condensation near 200 km, especially for C2H2 and C2H4 (Wong et al. 2017). 4) We found haze that had an extinction coefficient approximately proportional to N2 density.

Published
2017
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84. The role of statin therapy in older adults: best practices and unmet challenges.

Author

Stone, John, Kumar, Manish, and Orkaby, Ariela R.

Subjects
CARDIOVASCULAR diseases, OLDER people, STATINS (Cardiovascular agents), LITERATURE reviews, EVIDENCE gaps, DRUG monitoring
Abstract

Cardiovascular disease (CVD) is associated with significant morbidity, functional decline, and mortality in older adults. The role of statins for primary CVD prevention in older adults remains unclear, largely due to systematic exclusion of these individuals in trials that inform current practice guidelines, leading to conflicting national and international practice recommendations for statin use for primary prevention of CVD in adults aged 75 and older. In this narrative review, we performed a literature review utilizing PubMed, and ultimately focus on seven major national and international guidelines of lipid lowering therapy. Through the lens of two clinical cases, we review physiologic changes in lipid metabolism with aging, discuss the relationship between cholesterol and cardiovascular events in older adults, examine the national and international guidelines and the available evidence informing these guidelines for statin use in primary prevention of CVD in older adults. Finally we review practical clinical considerations for drug monitoring and deprescribing in this population. Guidelines for the use of statins for primary CVD prevention in older adults is conflicting. Collectively, evidence to date suggests statin therapy may be beneficial for primary CVD prevention in older adults free of life-limiting comorbidities. Randomized controlled trials are currently underway to address current evidence gaps. [ABSTRACT FROM AUTHOR]

Published
2024
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85. Teaching and Learning Health Justice: Best Practices and Recommendations for Innovation

Author

Rentmeester, Christy A., Chapple, Helen S., Haddad, Amy M., and Stone, John R.

Abstract

We describe the development and implementation of an online graduate bioethics program that weaves a theme of health justice throughout the curriculum. Our account relies on a constructionist model of curriculum development and adult teaching and learning theory. Our curriculum draws upon core values of Jesuit higher education, including content with particular attention to justice for marginalized and vulnerable members of society and pedagogical strategies that cultivate students' capacities for critical thinking and engagement with ethics and justice issues in the context of healthcare. We propose four major contributions from the health justice literature as key content areas for inclusion in bioethics programs interested in focusing on health justice. We identify gaps in the literature and suggest how they might be addressed. Finally, we give examples of content, pedagogy, and preliminary findings from specific courses in our program, all in hopes of stimulating more conversation about how students learn about health justice.

Published
2016

87. Housing and the Pandemic

Author

Baum, Scott, primary, Baker, Emma, additional, Davies, Amanda, additional, Stone, John, additional, and Taylor, Elizabeth, additional

Published
2022
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88. Planning the COVID City

Author

Baum, Scott, primary, Baker, Emma, additional, Davies, Amanda, additional, Stone, John, additional, and Taylor, Elizabeth, additional

Published
2022
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92. The Future of COVID Cities

Author

Baum, Scott, primary, Baker, Emma, additional, Davies, Amanda, additional, Stone, John, additional, and Taylor, Elizabeth, additional

Published
2022
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93. Pandemic Cities

Author

Baum, Scott, primary, Baker, Emma, additional, Davies, Amanda, additional, Stone, John, additional, and Taylor, Elizabeth, additional

Published
2022
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99. Granzyme K– and amphiregulin-expressing cytotoxic T cells and activated extrafollicular B cells are potential drivers of IgG4-related disease

Author

Koga, Risako, primary, Maehara, Takashi, additional, Aoyagi, Ryuichi, additional, Munemura, Ryusuke, additional, Murakami, Yuka, additional, Doi, Atsushi, additional, Kono, Michihito, additional, Yamamoto, Hidetaka, additional, Niiro, Hiroaki, additional, Kiyoshima, Tamotsu, additional, Tanabe, Mika, additional, Nakano, Toshiaki, additional, Matsukuma, Yuta, additional, Kawano, Mitsuhiro, additional, Stone, John H., additional, Pillai, Shiv, additional, Nakamura, Seiji, additional, and Kawano, Shintaro, additional

Published
2023
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100. Assessing the impact of ex vivo perfusion on graft immunogenicity

Author

Stone, John and Fildes, James

Subjects
616.07, Lung transplantation, Kidney transplantation, Direct presentation, Acute rejection, Ex vivo normothermic perfusion
Abstract

Whilst the major caveat to the success of organ transplantation remains the severe lack of donor organs, rejection is still a primary confounding factor to transplant outcomes. This is an allospecific response that occurs when the recipient immune system recognises conserved proteins on donor-derived cells as 'non-self'. Currently, all immunosuppressive regimes target the recipient immune response, ignoring the large donor immune repertoire despite these cells playing a central role in acute rejection. This is likely as a result of a lack of understanding of the temporal migration of the donor compartment and its contribution to the inflammatory cascade that ensues. The development of ex vivo perfusion provides the opportunity to assess this in isolation, with no confounding factors. Furthermore, inducing the mobilisation of passenger leukocytes on an ex vivo circuit allows their removal prior to transplantation. Reducing the inflammatory burden of donor organs has the potential to impact on the clinical outcome of patients, manifesting as a reduction in the incidence or severity of acute rejection. The aim of this PhD thesis was to characterise the donor immune compartment of lungs and kidneys, to assess the impact of ex vivo perfusion on this, and determine the post-transplant impact of removing a proportion of these cells. For this purpose, donor lungs were perfused using ex vivo lung perfusion (EVLP) and the immune compartment characterised. A comparison of EVLP versus standard transplanted lungs was performed using a porcine transplant model. Clinical parameters were recorded and a histological assessment of cellular infiltration was performed to diagnose the incidence of acute rejection. To determine if these results were translatable to other organs, a porcine model of kidney ex vivo perfusion was established. In both models, a significant efflux of donor leukocytes was observed and inflammatory mediators detected. In a transplant model of EVLP, reducing the transfer of these passenger leukocytes translated into improved clinical outcomes, manifesting as a lower incidence of acute rejection, for animals receiving EVLP lungs compared to a standard transplant. Similar benefit is likely to occur following transplantation of perfused kidneys. This study describes for the first time the contribution of donor organs to the inflammatory processes that ensue following transplantation. It is clear that this untargeted population is of significant importance in clinical outcomes. Immunomodulatory strategies to alter the donor immune environment prior to transplantation therefore warrant development.

Published
2017

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