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7. Harnessing Digital Pathology And Causal Learning To Improve Eosinophilic Esophagitis Dietary Treatment Assignment

Author

Aknin, Eliel, Larey, Ariel, Caldwell, Julie M., Collins, Margaret H., Abonia, Juan P., Aceves, Seema S., Arva, Nicoleta C., Chehade, Mirna, Dellon, Evan S., Gonsalves, Nirmala, Gupta, Sandeep K., Leung, John, Peterson, Kathryn A., Shoda, Tetsuo, Spergel, Jonathan M., Rothenberg, Marc E., and Savir, Yonatan

Subjects
Computer Science - Machine Learning
Abstract

Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven, allergic inflammatory condition of the esophagus associated with elevated esophageal eosinophils. EoE is a top cause of chronic dysphagia after GERD. Diagnosis of EoE relies on counting eosinophils in histological slides, a manual and time-consuming task that limits the ability to extract complex patient-dependent features. The treatment of EoE includes medication and food elimination. A personalized food elimination plan is crucial for engagement and efficiency, but previous attempts failed to produce significant results. In this work, on the one hand, we utilize AI for inferring histological features from the entire biopsy slide, features that cannot be extracted manually. On the other hand, we develop causal learning models that can process this wealth of data. We applied our approach to the 'Six-Food vs. One-Food Eosinophilic Esophagitis Diet Study', where 112 symptomatic adults aged 18-60 years with active EoE were assigned to either a six-food elimination diet (6FED) or a one-food elimination diet (1FED) for six weeks. Our results show that the average treatment effect (ATE) of the 6FED treatment compared with the 1FED treatment is not significant, that is, neither diet was superior to the other. We examined several causal models and show that the best treatment strategy was obtained using T-learner with two XGBoost modules. While 1FED only and 6FED only provide improvement for 35%-38% of the patients, which is not significantly different from a random treatment assignment, our causal model yields a significantly better improvement rate of 58.4%. This study illustrates the significance of AI in enhancing treatment planning by analyzing molecular features' distribution in histological slides through causal learning. Our approach can be harnessed for other conditions that rely on histology for diagnosis and treatment., Comment: 11 pages, 5 figures

Published
2023

9. Acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand management of acute disease.

Author

Xu, Junhua, Cai, Hongwei, Wu, Zhuhao, Li, Xiang, Tian, Chunhui, Ao, Zheng, Niu, Vivian C, Xiao, Xiao, Jiang, Lei, Khodoun, Marat, Rothenberg, Marc, Mackie, Ken, Chen, Jun, Lee, Luke P, and Guo, Feng

Subjects
Skin, Animals, Mice, Acute Disease, Drug Delivery Systems, Administration, Cutaneous, Acoustics, Female, Rare Diseases, Orphan Drug, Biotechnology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being
Abstract

Transdermal drug delivery provides convenient and pain-free self-administration for personalized therapy. However, challenges remain in treating acute diseases mainly due to their inability to timely administrate therapeutics and precisely regulate pharmacokinetics within a short time window. Here we report the development of active acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand acute disease management. Through the integration of active acoustic metamaterials, a compact therapeutic patch is integrated for penetration of skin stratum corneum and active percutaneous transport of therapeutics with precise control of dose and rate over time. Moreover, the patch device quantitatively regulates the dosage and release kinetics of therapeutics and achieves better delivery performance in vivo than through subcutaneous injection. As a proof-of-concept application, we show our method can reverse life-threatening acute allergic reactions in a female mouse model of anaphylaxis via a multi-burst delivery of epinephrine, showing better efficacy than a fixed dosage injection of epinephrine, which is the current gold standard 'self-injectable epinephrine' strategy. This innovative method may provide a promising means to manage acute disease for personalized medicine.

Published
2023

10. Harnessing Artificial Intelligence to Infer Novel Spatial Biomarkers for the Diagnosis of Eosinophilic Esophagitis

Author

Larey, Ariel, Aknin, Eliel, Daniel, Nati, Osswald, Garrett A., Caldwell, Julie M., Rochman, Mark, Wasserman, Tanya, Collins, Margaret H., Arva, Nicoleta C., Yang, Guang-Yu, Rothenberg, Marc E., and Savir, Yonatan

Subjects
Computer Science - Artificial Intelligence, Computer Science - Computer Vision and Pattern Recognition, Quantitative Biology - Quantitative Methods
Abstract

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory condition of the esophagus associated with elevated esophageal eosinophils. Second only to gastroesophageal reflux disease, EoE is one of the leading causes of chronic refractory dysphagia in adults and children. EoE diagnosis requires enumerating the density of esophageal eosinophils in esophageal biopsies, a somewhat subjective task that is time-consuming, thus reducing the ability to process the complex tissue structure. Previous artificial intelligence (AI) approaches that aimed to improve histology-based diagnosis focused on recapitulating identification and quantification of the area of maximal eosinophil density. However, this metric does not account for the distribution of eosinophils or other histological features, over the whole slide image. Here, we developed an artificial intelligence platform that infers local and spatial biomarkers based on semantic segmentation of intact eosinophils and basal zone distributions. Besides the maximal density of eosinophils (referred to as Peak Eosinophil Count [PEC]) and a maximal basal zone fraction, we identify two additional metrics that reflect the distribution of eosinophils and basal zone fractions. This approach enables a decision support system that predicts EoE activity and classifies the histological severity of EoE patients. We utilized a cohort that includes 1066 biopsy slides from 400 subjects to validate the system's performance and achieved a histological severity classification accuracy of 86.70%, sensitivity of 84.50%, and specificity of 90.09%. Our approach highlights the importance of systematically analyzing the distribution of biopsy features over the entire slide and paves the way towards a personalized decision support system that will assist not only in counting cells but can also potentially improve diagnosis and provide treatment prediction., Comment: AL, EA, and ND have contributed equally to this work and share first authorship. YS is the corresponding author, e-mail: yoni.savir@technion.ac.il

Published
2022

11. Nonepithelial Gene Expression Correlates With Symptom Severity in Adults With Eosinophilic Esophagitis

Author

Kim, Seung, Ben-Baruch Morgenstern, Netali, Osonoi, Kasumi, Aceves, Seema S., Arva, Nicoleta C., Chehade, Mirna, Collins, Margaret H., Dellon, Evan S., Falk, Gary W., Furuta, Glenn T., Gonsalves, Nirmala P., Gupta, Sandeep K., Hirano, Ikuo, Hiremath, Girish, Katzka, David A., Khoury, Paneez, Leung, John, Pesek, Robbie, Peterson, Kathryn A., Pletneva, Maria A., Spergel, Jonathan M., Wechsler, Joshua B., Yang, Guang-Yu, Rothenberg, Marc E., and Shoda, Tetsuo

Published
2024
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12. Long-term durability between parent and child patient-reported outcomes in eosinophilic esophagitis

Author

Martin, Lisa J., Zhang, Xue, Chehade, Mirna, Davis, Carla M., Dellon, Evan S., Falk, Gary W., Gupta, Sandeep K., Hirano, Ikuo, Hiremath, Girish S., Katzka, David A., Khoury, Paneez, Leung, John, Menard-Katcher, Paul, Gonsalves, Nirmala, Pesek, Robert D., Spergel, Jonathan M., Wechsler, Joshua B., Kliewer, Kara, Arva, Nicoleta C., Collins, Margaret H., Pletneva, Maria, Yang, Guang-Yu, Furuta, Glenn T., Rothenberg, Marc E., and Aceves, Seema S.

Published
2024
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16. Caregiver worry about COVID-19 as a predictor of social mitigation behaviours and SARS-CoV-2 infection in a 12-city U.S. surveillance study of households with children

Author

Brunwasser, Steven M., Gebretsadik, Tebeb, Satish, Anisha, Cole, Jennifer C., Dupont, William D., Joseph, Christine, Bendixsen, Casper G., Calatroni, Agustin, Arbes, Samuel J., Jr, Fulkerson, Patricia C., Sanders, Joshua, Bacharier, Leonard B., Camargo, Jr, Carlos A., Johnson, Christine Cole, Furuta, Glenn T., Gruchalla, Rebecca S., Gupta, Ruchi S., Khurana Hershey, Gurjit K., Jackson, Daniel J., Kattan, Meyer, Liu, Andrew, O'Connor, George T., Rivera-Spoljaric, Katherine, Phipatanakul, Wanda, Rothenberg, Marc E., Seibold, Max A., Seroogy, Christine M., Teach, Stephen J., Zoratti, Edward M., Togias, Alkis, and Hartert, Tina V.

Published
2025
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17. Losartan Treatment Reduces Esophageal Eosinophilic Inflammation in a Subset of Eosinophilic Esophagitis

Author

Wechsler, Joshua, Davis, Carla, Furuta, Glenn, Khoury, Paneez, Gupta, Sandeep K., Spergel, Jonathan, Leung, John, Menard-Katcher, Paul, Falk, Gary, Gonsalves, Nirmala Prabu, Peterson, Kathryn, Abonia, J. Pablo, Rudman Spergel, Amanda K., Hirano, Ikuo, Shoda, Tetsuo, Zhang, Xue, Martin, Lisa J., Mukkada, Vincent A., Putnam, Philip E., Blacklidge, Melodie, Neilson, Derek, Collins, Margaret H., Yang, Guang-Yu, Capocelli, Kelley E., Foote, Heather, Eby, Mike, Dong, Stephanie, Aceves, Seema S., and Rothenberg, Marc E.

Published
2024
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18. Clinical and molecular correlates of the Index of Severity for Eosinophilic Esophagitis

Author

Sato, Hiroki, Dellon, Evan S., Aceves, Seema S., Arva, Nicoleta C., Chehade, Mirna, Collins, Margaret H., Davis, Carla M., Falk, Gary W., Furuta, Glenn T., Gonsalves, Nirmala P., Gupta, Sandeep K., Hirano, Ikuo, Hiremath, Girish, Katzka, David A., Khoury, Paneez, Leung, John, Menard-Katcher, Paul, Pesek, Robbie, Peterson, Kathryn A., Pletneva, Maria A., Spergel, Jonathan M., Wechsler, Joshua B., Yang, Guang-Yu, Rothenberg, Marc E., and Shoda, Tetsuo

Published
2024
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27. PECNet: A Deep Multi-Label Segmentation Network for Eosinophilic Esophagitis Biopsy Diagnostics

Author

Daniel, Nati, Larey, Ariel, Aknin, Eliel, Osswald, Garrett A., Caldwell, Julie M., Rochman, Mark, Collins, Margaret H., Yang, Guang-Yu, Arva, Nicoleta C., Capocelli, Kelley E., Rothenberg, Marc E., and Savir, Yonatan

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning, Electrical Engineering and Systems Science - Image and Video Processing, Quantitative Biology - Quantitative Methods
Abstract

Background. Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus associated with elevated numbers of eosinophils. Disease diagnosis and monitoring requires determining the concentration of eosinophils in esophageal biopsies, a time-consuming, tedious and somewhat subjective task currently performed by pathologists. Methods. Herein, we aimed to use machine learning to identify, quantitate and diagnose EoE. We labeled more than 100M pixels of 4345 images obtained by scanning whole slides of H&E-stained sections of esophageal biopsies derived from 23 EoE patients. We used this dataset to train a multi-label segmentation deep network. To validate the network, we examined a replication cohort of 1089 whole slide images from 419 patients derived from multiple institutions. Findings. PECNet segmented both intact and not-intact eosinophils with a mean intersection over union (mIoU) of 0.93. This segmentation was able to quantitate intact eosinophils with a mean absolute error of 0.611 eosinophils and classify EoE disease activity with an accuracy of 98.5%. Using whole slide images from the validation cohort, PECNet achieved an accuracy of 94.8%, sensitivity of 94.3%, and specificity of 95.14% in reporting EoE disease activity. Interpretation. We have developed a deep learning multi-label semantic segmentation network that successfully addresses two of the main challenges in EoE diagnostics and digital pathology, the need to detect several types of small features simultaneously and the ability to analyze whole slides efficiently. Our results pave the way for an automated diagnosis of EoE and can be utilized for other conditions with similar challenges.

Published
2021

28. Machine learning approach for biopsy-based identification of eosinophilic esophagitis reveals importance of global features

Author

Czyzewski, Tomer, Daniel, Nati, Rochman, Mark, Caldwell, Julie M., Osswald, Garrett A., Collins, Margaret H., Rothenberg, Marc E., and Savir, Yonatan

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning, Electrical Engineering and Systems Science - Image and Video Processing, Quantitative Biology - Quantitative Methods
Abstract

Goal: Eosinophilic esophagitis (EoE) is an allergic inflammatory condition characterized by eosinophil accumulation in the esophageal mucosa. EoE diagnosis includes a manual assessment of eosinophil levels in mucosal biopsies - a time-consuming, laborious task that is difficult to standardize. One of the main challenges in automating this process, like many other biopsy-based diagnostics, is detecting features that are small relative to the size of the biopsy. Results: In this work, we utilized hematoxylin- and eosin-stained slides from esophageal biopsies from patients with active EoE and control subjects to develop a platform based on a deep convolutional neural network (DCNN) that can classify esophageal biopsies with an accuracy of 85%, sensitivity of 82.5%, and specificity of 87%. Moreover, by combining several downscaling and cropping strategies, we show that some of the features contributing to the correct classification are global rather than specific, local features. Conclusions: We report the ability of artificial intelligence to identify EoE using computer vision analysis of esophageal biopsy slides. Further, the DCNN features associated with EoE are based on not only local eosinophils but also global histologic changes. Our approach can be used for other conditions that rely on biopsy-based histologic diagnostics.

Published
2021

30. A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells

Author

Mahoney, Matthew, Damalanka, Vishnu C, Tartell, Michael A, Chung, Dong hee, Lourenço, André Luiz, Pwee, Dustin, Bridwell, Anne E Mayer, Hoffmann, Markus, Voss, Jorine, Karmakar, Partha, Azouz, Nurit P, Klingler, Andrea M, Rothlauf, Paul W, Thompson, Cassandra E, Lee, Melody, Klampfer, Lidija, Stallings, Christina L, Rothenberg, Marc E, Pöhlmann, Stefan, Whelan, Sean PJ, O’Donoghue, Anthony J, Craik, Charles S, and Janetka, James W

Subjects
Biological Sciences, Medicinal and Biomolecular Chemistry, Chemical Sciences, Biodefense, Pneumonia, Vaccine Related, Infectious Diseases, Emerging Infectious Diseases, Prevention, Lung, Pneumonia & Influenza, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Animals, Benzamidines, Benzothiazoles, COVID-19, Cell Line, Drug Design, Epithelial Cells, Esters, Guanidines, Humans, Mice, Middle East Respiratory Syndrome Coronavirus, Oligopeptides, SARS-CoV-2, Serine Endopeptidases, Small Molecule Libraries, Substrate Specificity, Virus Internalization, COVID-19 Drug Treatment, antiviral, protease inhibitor, structure-based drug discovery, PS-SCL
Abstract

The host cell serine protease TMPRSS2 is an attractive therapeutic target for COVID-19 drug discovery. This protease activates the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of other coronaviruses and is essential for viral spread in the lung. Utilizing rational structure-based drug design (SBDD) coupled to substrate specificity screening of TMPRSS2, we have discovered covalent small-molecule ketobenzothiazole (kbt) TMPRSS2 inhibitors which are structurally distinct from and have significantly improved activity over the existing known inhibitors Camostat and Nafamostat. Lead compound MM3122 (4) has an IC50 (half-maximal inhibitory concentration) of 340 pM against recombinant full-length TMPRSS2 protein, an EC50 (half-maximal effective concentration) of 430 pM in blocking host cell entry into Calu-3 human lung epithelial cells of a newly developed VSV-SARS-CoV-2 chimeric virus, and an EC50 of 74 nM in inhibiting cytopathic effects induced by SARS-CoV-2 virus in Calu-3 cells. Further, MM3122 blocks Middle East respiratory syndrome coronavirus (MERS-CoV) cell entry with an EC50 of 870 pM. MM3122 has excellent metabolic stability, safety, and pharmacokinetics in mice, with a half-life of 8.6 h in plasma and 7.5 h in lung tissue, making it suitable for in vivo efficacy evaluation and a promising drug candidate for COVID-19 treatment.

Published
2021

32. One-food versus 4-food elimination diet for pediatric eosinophilic esophagitis: A multisite randomized trial

Author

Kliewer, Kara L., Abonia, J. Pablo, Aceves, Seema S., Atkins, Dan, Bonis, Peter A., Capocelli, Kelley E., Chehade, Mirna, Collins, Margaret H., Dellon, Evan S., Fei, Lin, Furuta, Glenn T., Gupta, Sandeep K., Kagalwalla, Amir, Leung, John, Mir, Sabina, Mukkada, Vincent A., Pesek, Robbie, Rosenberg, Chen, Shoda, Tetsuo, Spergel, Jonathan M., Sun, Qin, Wechsler, Joshua B., Yang, Guang-Yu, and Rothenberg, Marc E.

Published
2024
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33. Advancing patient care through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)

Author

Aceves, Seema, Collins, Margaret H, Rothenberg, Marc E, Furuta, Glenn T, Gonsalves, Nirmala, Researchers, Consortium of Eosinophilic Gastrointestinal Disease, Abonia, J Pablo, Almonte, Samuel, Andrews, Rachel, Arrington, Ashley, Arva, Nicoleta, Atkins, Fred, Bailey, Dominique, Berry, Alexis, Besl, Bridget, Bolton, Scott, Bonis, Peter, Book, Wendy, Bray, Kimberly, Brown, Teresa, Burger, Cassandra, Burke, Deirdre, Cahoon, Jonathon, Capocelli, Kelley, Chehade, Mirna, Collins, Margaret, Davis, Carla, Dellon, Evan, DeMarshall, Maureen, DiTommaso, Lauren, Dohil, Ranjan, Eby, Michael, Falk, Gary, Fleischer, David, Foote, Heather, Foss, Kelci, Friedlander, Joel, Fulkerson, Patricia, Furuta, Glenn, Geno, Debra, Greuter, Thomas, Gupta, Sandeep, Hamilton, Frank, Harris, Kirk, Harris, Jennifer, Hirano, Ikuo, Hiremath, Girish, Holland-Thomas, Nicole, Jacinto, Lea, Kagalwalla, Amir, Kaseta, Timothy, Katzka, David, Keeley, Kaitlin, Khosh-Hemmat, Emad, Khoury, Paneez, King, Eileen, Kliewer, Kara, Klion, Amy, Knowles, Jennifer, Kocher, Kendra, Kodroff, Ellyn, Krischer, Jeffrey, Kyle, Shay, Leung, John, Levy, Meredith, Liacouras, Chris, Mack, Denise, Martin, Lisa, Martin, Ellen, McCright-Gill, Talaya, Menard-Katcher, Paul, Menard-Katcher, Calies, Mendoza, Gabriela, Mingler, Melissa, Minnicozzi, Mike, Muir, Amanda, Mukkada, Vincent, MurrayPetzold, Cristin, Newbury, Robert, Nhu, Quan, Oyibo, Oghenekpaobor, Paliana, Allisa, Pan, Zhaoxing, Pesek, Robbie, Peterson, Kathryn, Poppendeck, Heidi, Putnam, Philip, Rivera, Fabian, Rothenberg, Marc, Rudman-Spergel, Amanda, Sable, Kathleen, Schoepfer, Alain, Scott, Melissa, Sheridan, Rachel, Sinanovic, Selma, Spergel, Jonathan, Strobel, MaryJo, and Sun, Kiki

Subjects
Biomedical and Clinical Sciences, Immunology, Clinical Research, Digestive Diseases, Clinical Trials and Supportive Activities, Evaluation of treatments and therapeutic interventions, Detection, screening and diagnosis, 6.9 Resources and infrastructure (treatment evaluation), 4.5 Resources and infrastructure (detection), Good Health and Well Being, Biomedical Research, Clinical Trials as Topic, Enteritis, Eosinophilia, Eosinophilic Esophagitis, Gastritis, National Institutes of Health (U.S.), United States, Eosinophils, gastrointestinal, consortium, allergy, esophagitis, advocacy, Consortium of Eosinophilic Gastrointestinal Disease Researchers, Allergy
Abstract

Recent advances in rare disease research are accelerated by the work of consortia that have been supported by the National Institutes of Health. Development of such consortia rely on multidisciplinary relationships and engagement with patient advocacy groups, as well as the National Institutes of Health and industry and academic partners. In this rostrum we present the development of such a process that focuses on eosinophilic gastrointestinal diseases. Principal investigators, patient advocacy groups, research assistants, and trainees work together to perform natural history studies that promote clinical trial readiness tools, conduct clinical trials, train a new generation of investigators, and perform innovative pilot studies.

Published
2020

34. Single cell transcriptomic analysis of HPV16-infected epithelium identifies a keratinocyte subpopulation implicated in cancer

Author

Bedard, Mary C., Chihanga, Tafadzwa, Carlile, Adrean, Jackson, Robert, Brusadelli, Marion G., Lee, Denis, VonHandorf, Andrew, Rochman, Mark, Dexheimer, Phillip J., Chalmers, Jeffrey, Nuovo, Gerard, Lehn, Maria, Williams, David E. J., Kulkarni, Aditi, Carey, Molly, Jackson, Amanda, Billingsley, Caroline, Tang, Alice, Zender, Chad, Patil, Yash, Wise-Draper, Trisha M., Herzog, Thomas J., Ferris, Robert L., Kendler, Ady, Aronow, Bruce J., Kofron, Matthew, Rothenberg, Marc E., Weirauch, Matthew T., Van Doorslaer, Koenraad, Wikenheiser-Brokamp, Kathryn A., Lambert, Paul F., Adam, Mike, Steven Potter, S., and Wells, Susanne I.

Published
2023
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36. Type 2 Immunity and Age Modify Gene Expression of Coronavirus-induced Disease 2019 Receptors in Eosinophilic Gastrointestinal Disorders.

Author

Chiang, Austin, Duong, Loan, Shoda, Tetsuo, Nhu, Quan, Ruffner, Melanie, Hara, Takeo, Aaron, Bailey, Joplin, Erik, Manresa, Mario, Abonia, J, Dellon, Evan, Hirano, Ikuo, Gonsalves, Nirmala, Gupta, Sandeep, Furuta, Glenn, Rothenberg, Marc, Lewis, Nathan, Muir, Amanda, and Aceves, Seema

Subjects
Adult, COVID-19, Child, Enteritis, Eosinophilia, Gastritis, Gene Expression, Humans, Peptidyl-Dipeptidase A, SARS-CoV-2
Abstract

Infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can lead to coronavirus-induced disease 2019 (COVID-19). The gastrointestinal (GI) tract is now an appreciated portal of infection. SARS-CoV-2 enters host cells via angiotensin-converting enzyme-2 (ACE2) and the serine protease TMPRSS2. Eosinophilic gastrointestinal disorders (EGIDs) are inflammatory conditions caused by chronic type 2 (T2) inflammation. the effects of the T2 atopic inflammatory milieu on SARS-COV-2 viral entry gene expression in the GI tract is poorly understood. We analyzed tissue ACE2 and TMPRSS2 gene expression in pediatric eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), and in normal adult esophagi using publicly available RNA-sequencing datasets. Similar to findings evaluating the airway, there was no difference in tissue ACE2/TMPRSS2 expression in EoE or EG when compared with control non-EoE/EG esophagus/stomach. ACE2 gene expression was significantly lower in esophagi from children with or without EoE and from adults with EoE as compared with normal adult esophagi. Type 2 immunity and pediatric age could be protective for infection by SARS-CoV-2 in the gastrointestinal tract because of decreased expression of ACE2.

Published
2021

37. Breakthroughs in understanding and treating eosinophilic gastrointestinal diseases presented at the CEGIR/TIGERs Symposium at the 2022 American Academy of Allergy, Asthma & Immunology Meeting

Author

Chehade, Mirna, Wright, Benjamin L., Atkins, Dan, Aceves, Seema S., Ackerman, Steven J., Assa’ad, Amal H., Bauer, Maureen, Collins, Margaret H., Commins, Scott P., Davis, Carla M., Dellon, Evan S., Doerfler, Bethan, Gleich, Gerald J., Gupta, Sandeep K., Hill, David A., Jensen, Elizabeth T., Katzka, David, Kliewer, Kara, Kodroff, Ellyn, Kottyan, Leah C., Kyle, Shay, Muir, Amanda B., Pesek, Robert D., Peterson, Kathryn, Shreffler, Wayne G., Spergel, Jonathan M., Strobel, Mary Jo, Wechsler, Joshua, Zimmermann, Nives, Furuta, Glenn T., and Rothenberg, Marc E.

Published
2023
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38. Efficacy and safety of dupilumab up to 52 weeks in adults and adolescents with eosinophilic oesophagitis (LIBERTY EoE TREET study): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial

Author

Rothenberg, Marc E, Dellon, Evan S, Collins, Margaret H, Hirano, Ikuo, Chehade, Mirna, Bredenoord, Albert J, Lucendo, Alfredo J, Spergel, Jonathan M, Sun, Xian, Hamilton, Jennifer D, Mortensen, Eric, Laws, Elizabeth, Maloney, Jennifer, Mannent, Leda P, McCann, Eilish, Liu, Xia, Glotfelty, Lila, and Shabbir, Arsalan

Published
2023
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39. Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study

Author

Pablo Abonia, J., Aceves, Seema, Almonte, Samuel, Andrews, Rachel, Anvari, Sara, Arrington, Ashley, Arva, Nicoleta, Atkins, Fred, Bailey, Dominique, Berry, Alexis, Besl, Bridget, Bolton, Scott, Bonis, Peter, Book, Wendy, Bray, Kimberly, Brown, Teresa, Burger, Cassandra, Burke, Deirdre, Cahoon, Jonathon, Capocelli, Kelley, Chehade, Mirna, Chiou, Eric, Collins, Margaret, Davis, Carla, Dellon, Evan, DeMarshall, Maureen, DiTommaso, Lauren, Dohil, Ranjan, Eby, Michael, Falk, Gary, Fleischer, David, Foote, Heather, Foss, Kelci, Friedlander, Joel, Fulkerson, Patricia, Furuta, Glenn, Geno, Debra, Gonsalves, Nirmala, Greuter, Thomas, Gupta, Sandeep, Hamilton, Frank, Harris, Kirk, Harris, Jennifer, Hirano, Ikuo, Hiremath, Girish, Holland-Thomas, Nicole, Jacinto, Lea, Kagalwalla, Amir, Kaseta, Timothy, Katzka, David, Keeley, Kaitlin, Khosh-Hemmat, Emad, Khoury, Paneez, King, Eileen, Kliewer, Kara, Klion, Amy, Knowles, Jennifer, Kocher, Kendra, Kodroff, Ellyn, Krischer, Jeffrey, Kyle, Shay, Leung, John, Levy, Meredith, Liacouras, Chris, Mack, Denise, Martin, Lisa, Martin, Ellen, McCright-Gill, Talaya, Menard-Katcher, Paul, Menard-Katcher, Calies, Mendoza, Gabriela, Mingler, Melissa, Minnicozzi, Mike, Muir, Amanda, Mukkada, Vincent, Murray-Petzold, Cristin, Newbury, Robert, Nhu, Quan, Olive, Anthony, Oyibo, Oghenekpaobor (Joel), Paliana, Allisa, Pan, Zhaoxing, Pesek, Robbie, Peterson, Kathryn, Poppendeck, Heidi, Putnam, Philip, Rivera, Fabian, Rothenberg, Marc, Spergel, Amanda Rudman, Sable, Kathleen, Schoepfer, Alain, Scott, Melissa, Sheridan, Rachel, Sinanovic, Selma, Spergel, Jonathan, Strobel, Mary Jo, Sun, Kiki, Tasco, Amy, Tholen, Crystal, Thompson, Katherine, Tomkinson, Tiffany, Tran, Daisy, Tylicki, Alexandra, Urv, Tiina, Wang, Mei-Lun, Wechsler, Joshua, Wershil, Barry, Wheatley, Lisa, Wilkey, Leah, Yang, Guang-Yu, Zalewski, Angelika, Zicarelli, Amy, Shoda, Tetsuo, Collins, Margaret H., Rochman, Mark, Wen, Ting, Caldwell, Julie M., Mack, Lydia E., Osswald, Garrett A., Besse, John A., Haberman, Yael, Aceves, Seema S., Arva, Nicoleta C., Capocelli, Kelley E., Davis, Carla M., Dellon, Evan S., Falk, Gary W., Gupta, Sandeep K., Mukkada, Vincent A., Putnam, Philip E., Spergel, Jonathan M., Wechsler, Joshua B., Furuta, Glenn T., Denson, Lee A., and Rothenberg, Marc E.

Published
2022
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40. Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell–Fibroblast Crosstalk

Author

Abonia, J. Pablo, Aceves, Seema, Almonte, Samuel, Andrews, Rachel, Arrington, Ashley, Arva, Nicoleta, Atkins, Fred, Bailey, Dominique, Berry, Alexis, Besl, Bridget, Bolton, Scott, Bonis, Peter, Book, Wendy, Bray, Kimberly, Brown, Teresa, Burger, Cassandra, Burke, Deirdre, Cahoon, Jonathon, Capocelli, Kelley, Chehade, Mirna, Collins, Margaret, Davis, Carla, Dellon, Evan, DeMarshall, Maureen, DiTommaso, Lauren, Dohil, Ranjan, Eby, Michael, Falk, Gary, Fleischer, David, Foote, Heather, Foss, Kelci, Friedlander, Joel, Fulkerson, Patricia, Furuta, Glenn, Geno, Debra, Gonsalves, Nirmala, Greuter, Thomas, Gupta, Sandeep, Hamilton, Frank, Harris, Kirk, Harris, Jennifer, Hirano, Ikuo, Hiremath, Girish, Holland-Thomas, Nicole, Jacinto, Lea, Kagalwalla, Amir, Kaseta, Timothy, Katzka, David, Keeley, Kaitlin, Khosh-Hemmat, Emad, Khoury, Paneez, King, Eileen, Kliewer, Kara, Klion, Amy, Knowles, Jennifer, Kocher, Kendra, Kodroff, Ellyn, Krischer, Jeffrey, Kyle, Shay, Leung, John, Levy, Meredith, Liacouras, Chris, Mack, Denise, Martin, Lisa, Martin, Ellen, McCright-Gill, Talaya, Menard-Katcher, Paul, Menard-Katcher, Calies, Mendoza, Gabriela, Mingler, Melissa, Minnicozzi, Mike, Muir, Amanda, Mukkada, Vincent, MurrayPetzold, Cristin, Newbury, Robert, Nhu, Quan, Oyibo, Oghenekpaobor (Joel), Paliana, Allisa, Pan, Zhaoxing, Pesek, Robbie, Peterson, Kathryn, Poppendeck, Heidi, Putnam, Philip, Rivera, Fabian, Rothenberg, Marc, Spergel, Amanda Rudman, Sable, Kathleen, Schoepfer, Alain, Scott, Melissa, Sheridan, Rachel, Sinanovic, Selma, Spergel, Jonathan, Strobel, MaryJo, Sun, Kiki, Tasco, Amy, Tholen, Crystal, Thompson, Katherine, Tomkinson, Tiffany, Tran, Daisy, Tylicki, Alexandra, Urv, Tiina, Wang, Mei-Lun, Wechsler, Joshua, Wershil, Barry, Wheatley, Lisa, Wilkey, Leah, Yang, Guang-Yu, Zalewski, Angelika, Zicarelli, Amy, Shoda, Tetsuo, Wen, Ting, Caldwell, Julie M., Ben-Baruch Morgenstern, Netali, Osswald, Garrett A., Rochman, Mark, Mack, Lydia E., Felton, Jennifer M., Arva, Nicoleta C., Atkins, Dan, Bonis, Peter A., Capocelli, Kelley E., Collins, Margaret H., Dellon, Evan S., Falk, Gary W., Gupta, Sandeep K., Menard-Katcher, Paul A., Mukkada, Vincent A., Putnam, Philip E., Rudman Spergel, Amanda K., Spergel, Jonathan M., Wechsler, Joshua B., Aceves, Seema S., Furuta, Glenn T., and Rothenberg, Marc E.

Published
2022
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41. Benralizumab for eosinophilic gastritis: a single-site, randomised, double-blind, placebo-controlled, phase 2 trial

Author

Kliewer, Kara L, Murray-Petzold, Cristin, Collins, Margaret H, Abonia, Juan P, Bolton, Scott M, DiTommaso, Lauren A, Martin, Lisa J, Zhang, Xue, Mukkada, Vincent A, Putnam, Philip E, Kellner, Erinn S, Devonshire, Ashley L, Schwartz, Justin T, Kunnathur, Vidhya A, Rosenberg, Chen E, Lyles, John L, Shoda, Tetsuo, Klion, Amy D, and Rothenberg, Marc E

Published
2023
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44. Local type 2 immunity in eosinophilic gastritis

Author

Ben-Baruch Morgenstern, Netali, Shoda, Tetsuo, Rochman, Yrina, Caldwell, Julie M., Collins, Margaret H., Mukkada, Vincent, Putnam, Philip E., Bolton, Scott M., Felton, Jennifer M., Rochman, Mark, Murray-Petzold, Cristin, Kliewer, Kara L., and Rothenberg, Marc E.

Published
2023
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45. Development of a Practical Guide to Implement and Monitor Diet Therapy for Eosinophilic Esophagitis

Author

Aceves, Seema S., Abonia, Pablo, Atkins, Dan, Bonis, Peter A., Chehade, Mirna, Falk, Gary W., Furuta, Glenn T., Gupta, Sandeep K., Kagalwalla, Amir F., Kodroff, Ellyn, Kyle, Scholeigh, Leung, John, Menard-Katcher, Paul, Mir, Sabina, Mukkada, Vincent A., Pesek, Robert, Rothenberg, Marc E., Spergel, Jonathan M., Strobel, Mary Jo, Wechsler, Joshua B., Chang, Joy W., Kliewer, Kara, Haller, Emily, Lynett, Amanda, Doerfler, Bethany, Katzka, David A., Peterson, Kathryn A., Dellon, Evan S., and Gonsalves, Nirmala

Published
2023
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46. Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study

Author

Shoda, Tetsuo, Wen, Ting, Caldwell, Julie M, Collins, Margaret H, Besse, John A, Osswald, Garrett A, Abonia, J Pablo, Arva, Nicoleta C, Atkins, Dan, Capocelli, Kelley E, Dellon, Evan S, Falk, Gary W, Gonsalves, Nirmala, Gupta, Sandeep K, Hirano, Ikuo, Mukkada, Vincent A, Putnam, Philip E, Sheridan, Rachel M, Spergel, Amanda K Rudman, Spergel, Jonathan M, Wechsler, Joshua B, Yang, Guang-Yu, Aceves, Seema S, Furuta, Glenn T, Rothenberg, Marc E, and Researchers, Consortium of Eosinophilic Gastrointestinal Disease

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Clinical Research, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Adolescent, Adult, Biomarkers, Child, Cytokines, Endoscopy, Gastrointestinal, Enteritis, Eosinophilia, Female, Gastritis, Humans, Male, Biomarker, diagnostic panel, eosinophil, eosinophilic gastritis, transcriptome, Consortium of Eosinophilic Gastrointestinal Disease Researchers, Immunology, Allergy
Abstract

BackgroundEosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need among patients with EG for more precise diagnostic tools.ObjectiveWe aimed to develop tissue- and blood-based diagnostic platforms for EG.MethodsPatients with EG and control subjects without EG were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers-associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. EGDP18 scores were derived from the expression of 18 highly dysregulated genes, and blood EG scores were derived from dysregulated cytokine/chemokine levels.ResultsGastric biopsy specimens and blood samples from 185 subjects (patients with EG, n = 74; control subjects without EG, n = 111) were analyzed. The EGDP (1) identified patients with active EG (P < .0001, area under the curve ≥ 0.95), (2) effectively monitored disease activity in longitudinal samples (P = .0078), (3) highly correlated in same-patient samples (antrum vs body, r = 0.85, P < .0001), and (4) inversely correlated with gastric peak eosinophil levels (r = -0.83, P < .0001), periglandular circumferential collars (r = -0.73, P < .0001), and endoscopic nodularity (r = -0.45, P < .0001). For blood-based platforms, eotaxin-3, thymus and activation-regulated chemokine, IL-5, and thymic stromal lymphopoietin levels were significantly increased. Blood EG scores (1) distinguished patients with EG from control subjects without EG (P < .0001, area under the curve ≥ 0.91), (2) correlated with gastric eosinophil levels (plasma: r = 0.72, P = .0002; serum: r = 0.54, P = .0015), and (3) inversely correlated with EGDP18 scores (plasma: r = -0.64, P = .0015; serum: r = -0.46, P = .0084). Plasma eotaxin-3 levels strongly associated with gastric CCL26 expression (r = 0.81, P < .0001).ConclusionWe developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and clinical readiness tools for this emerging rare disease.

Published
2020

47. One-food versus six-food elimination diet therapy for the treatment of eosinophilic oesophagitis: a multicentre, randomised, open-label trial

Author

Kliewer, Kara L, Gonsalves, Nirmala, Dellon, Evan S, Katzka, David A, Abonia, Juan P, Aceves, Seema S, Arva, Nicoleta C, Besse, John A, Bonis, Peter A, Caldwell, Julie M, Capocelli, Kelley E, Chehade, Mirna, Cianferoni, Antonella, Collins, Margaret H, Falk, Gary W, Gupta, Sandeep K, Hirano, Ikuo, Krischer, Jeffrey P, Leung, John, Martin, Lisa J, Menard-Katcher, Paul, Mukkada, Vincent A, Peterson, Kathryn A, Shoda, Tetsuo, Rudman Spergel, Amanda K, Spergel, Jonathan M, Yang, Guang-Yu, Zhang, Xue, Furuta, Glenn T, and Rothenberg, Marc E

Published
2023
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49. High Discovery Rate of Duodenal and Gastric Eosinophilia in Patients With Unexplained Moderate–Severe Abdominal Symptoms: A Prospective US Multisite Study

Author

Talley, Nicholas J., Peterson, Kathryn A., Genta, Robert M., Chang, Alan T., Dellon, Evan S., Sandborn, William J., Lacy, Brian E., Chehade, Mirna, Hirano, Ikuo, Gonsalves, Nirmala, Lembo, Anthony, Schmitt, Colleen M., Rothenberg, Marc E., Jain, Neal, Pletneva, Maria A., Turner, Kevin O., and Youngblood, Bradford A.

Published
2023
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