695 results on '"Utz, Paul J."'
Search Results
2. Unveiling the proteome-wide autoreactome enables enhanced evaluation of emerging CAR T cell therapies in autoimmunity
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Bodansky, Aaron, Yu, David J.L., Rallistan, Alysa, Kalaycioglu, Muge, Boonyaratanakornki, Jim, Green, Damian J., Gauthier, Jordan, Turtle, Cameron J., Zorn, Kelsey, O'Donovan, Brian, Mandel-Brehm, Caleigh, Asaki, James, Kortbawi, Hannah, Kung, Andrew F., Rackaityte, Elze, Wang, Chung-Yu, Saxena, Aditi, de Dios, Kimberly, Masi, Gianvito, Nowak, Richard J., O'Connor, Kevin C., Li, Hao, Diaz, Valentina E., Saloner, Rowan, Casaletto, Kaitlin B., Gontrum, Eva Q., Chan, Brandon, Kramer, Joel H., Wilson, Michael R., Utz, Paul J., Hill, Joshua A., Jackson, Shaun W., Anderson, Mark S., and DeRisi, Joseph L.
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T cells -- Health aspects ,Proteomics -- Analysis ,Cellular therapy -- Complications and side effects -- Patient outcomes ,Viral antibodies -- Health aspects ,Antibodies -- Health aspects ,Health care industry ,Analysis ,Complications and side effects ,Patient outcomes ,Health aspects - Abstract
Given the global surge in autoimmune diseases, it is critical to evaluate emerging therapeutic interventions. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments longitudinally are lacking. Here, we leveraged advances in programmable-phage immunoprecipitation methodology to explore the modulation, or lack thereof, of autoantibody profiles, proteome-wide, in both health and disease. Using a custom set of over 730,000 human-derived peptides, we demonstrated that each individual, regardless of disease state, possesses a distinct and complex constellation of autoreactive antibodies. For each individual, the set of resulting autoreactivites constituted a unique immunological fingerprint, or "autoreactome," that was remarkably stable over years. Using the autoreactome as a primary output, we evaluated the relative effectiveness of various immunomodulatory therapies in altering autoantibody repertoires. We found that therapies targeting B cell maturation antigen (BCMA) profoundly altered an individual's autoreactome, while anti-CD19 and anti-CD20 therapies had minimal effects. These data both confirm that the autoreactome comprises autoantibodies secreted by plasma cells and strongly suggest that BCMA or other plasma cell- targeting therapies may be highly effective in treating currently refractory autoantibody-mediated diseases., Introduction Autoantibodies have been identified in a wide range of autoimmune diseases (1-4). In many cases these autoantibodies are directly pathogenic (5-10), while in others they amplify or support T [...]
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- 2024
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3. KIR+CD8+ T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19
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Li, Jing, Zaslavsky, Maxim, Su, Yapeng, Guo, Jing, Sikora, Michael J, van Unen, Vincent, Christophersen, Asbjørn, Chiou, Shin-Heng, Chen, Liang, Li, Jiefu, Ji, Xuhuai, Wilhelmy, Julie, McSween, Alana M, Palanski, Brad A, Mallajosyula, Venkata Vamsee Aditya, Bracey, Nathan A, Dhondalay, Gopal Krishna R, Bhamidipati, Kartik, Pai, Joy, Kipp, Lucas B, Dunn, Jeffrey E, Hauser, Stephen L, Oksenberg, Jorge R, Satpathy, Ansuman T, Robinson, William H, Dekker, Cornelia L, Steinmetz, Lars M, Khosla, Chaitan, Utz, Paul J, Sollid, Ludvig M, Chien, Yueh-Hsiu, Heath, James R, Fernandez-Becker, Nielsen Q, Nadeau, Kari C, Saligrama, Naresha, and Davis, Mark M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Immunology ,Autoimmune Disease ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Good Health and Well Being ,Animals ,Autoimmune Diseases ,CD8-Positive T-Lymphocytes ,COVID-19 ,Humans ,Mice ,Receptors ,KIR ,T-Lymphocytes ,Regulatory ,General Science & Technology - Abstract
In this work, we find that CD8+ T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49+CD8+ regulatory T cells in mice and are increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8+ T cells efficiently eliminated pathogenic gliadin-specific CD4+ T cells from the leukocytes of celiac disease patients in vitro. We also find elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 patients, correlating with disease severity and vasculitis. Selective ablation of Ly49+CD8+ T cells in virus-infected mice led to autoimmunity after infection. Our results indicate that in both species, these regulatory CD8+ T cells act specifically to suppress pathogenic T cells in autoimmune and infectious diseases.
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- 2022
4. Antigen presentation by B cells enables epitope spreading across an MHC barrier
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Fahlquist-Hagert, Cecilia, Wittenborn, Thomas R., Terczyńska-Dyla, Ewa, Kastberg, Kristian Savstrup, Yang, Emily, Rallistan, Alysa Nicole, Markett, Quinton Raymond, Winther, Gudrun, Fonager, Sofie, Voss, Lasse F., Pedersen, Mathias K., van Campen, Nina, Ferapontov, Alexey, Jensen, Lisbeth, Huang, Jinrong, Nieland, John D., van der Poel, Cees E., Palmfeldt, Johan, Carroll, Michael C., Utz, Paul J., Luo, Yonglun, Lin, Lin, and Degn, Søren E.
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- 2023
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5. Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity
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Chakraborty, Saborni, Gonzalez, Joseph C, Sievers, Benjamin L, Mallajosyula, Vamsee, Chakraborty, Srijoni, Dubey, Megha, Ashraf, Usama, Cheng, Bowie Yik-Ling, Kathale, Nimish, Tran, Kim Quyen Thi, Scallan, Courtney, Sinnott, Aanika, Cassidy, Arianna, Chen, Steven T, Gelbart, Terri, Gao, Fei, Golan, Yarden, Ji, Xuhuai, Kim-Schulze, Seunghee, Prahl, Mary, Gaw, Stephanie L, Gnjatic, Sacha, Marron, Thomas U, Merad, Miriam, Arunachalam, Prabhu S, Boyd, Scott D, Davis, Mark M, Holubar, Marisa, Khosla, Chaitan, Maecker, Holden T, Maldonado, Yvonne, Mellins, Elizabeth D, Nadeau, Kari C, Pulendran, Bali, Singh, Upinder, Subramanian, Aruna, Utz, Paul J, Sherwood, Robert, Zhang, Sheng, Jagannathan, Prasanna, Tan, Gene S, and Wang, Taia T
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Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,Pneumonia & Influenza ,Lung ,Vaccine Related ,Pneumonia ,Prevention ,Biotechnology ,Immunization ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Respiratory ,Good Health and Well Being ,Antibodies ,Neutralizing ,Antibodies ,Viral ,Antibody Formation ,COVID-19 ,COVID-19 Vaccines ,Humans ,Prospective Studies ,SARS-CoV-2 ,Spike Glycoprotein ,Coronavirus ,Biological Sciences ,Medical and Health Sciences ,Medical biotechnology ,Biomedical engineering - Abstract
A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated immunoglobulin G (IgG) antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. To study the biology of afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG-Fc-gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from patients with COVID-19 induced inflammatory cytokine production and robust infiltration of the lung by immune cells. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by messenger RNA SARS-CoV-2 vaccines were highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. Vaccine-elicited IgG did not promote an inflammatory lung response. These results show that human IgG-FcγR interactions regulate inflammation in the lung and define distinct lung activities mediated by the IgG that are associated with protection against, or progression to, severe COVID-19.
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- 2022
6. Xist ribonucleoproteins promote female sex-biased autoimmunity
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Dou, Diana R., Zhao, Yanding, Belk, Julia A., Zhao, Yang, Casey, Kerriann M., Chen, Derek C., Li, Rui, Yu, Bingfei, Srinivasan, Suhas, Abe, Brian T., Kraft, Katerina, Hellström, Ceke, Sjöberg, Ronald, Chang, Sarah, Feng, Allan, Goldman, Daniel W., Shah, Ami A., Petri, Michelle, Chung, Lorinda S., Fiorentino, David F., Lundberg, Emma K., Wutz, Anton, Utz, Paul J., and Chang, Howard Y.
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- 2024
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7. Air pollution and pregnancy
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Aguilera, Juan, Konvinse, Katherine, Lee, Alexandra, Maecker, Holden, Prunicki, Mary, Mahalingaiah, Shruthi, Sampath, Vanitha, Utz, Paul J., Yang, Emily, and Nadeau, Kari C.
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- 2023
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8. Multi-omics analysis of mucosal and systemic immunity to SARS-CoV-2 after birth
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Wimmers, Florian, Burrell, Allison R., Feng, Yupeng, Zheng, Hong, Arunachalam, Prabhu S., Hu, Mengyun, Spranger, Sara, Nyhoff, Lindsay E., Joshi, Devyani, Trisal, Meera, Awasthi, Mayanka, Bellusci, Lorenza, Ashraf, Usama, Kowli, Sangeeta, Konvinse, Katherine C., Yang, Emily, Blanco, Michael, Pellegrini, Kathryn, Tharp, Gregory, Hagan, Thomas, Chinthrajah, R. Sharon, Nguyen, Tran T., Grifoni, Alba, Sette, Alessandro, Nadeau, Kari C., Haslam, David B., Bosinger, Steven E., Wrammert, Jens, Maecker, Holden T., Utz, Paul J., Wang, Taia T., Khurana, Surender, Khatri, Purvesh, Staat, Mary A., and Pulendran, Bali
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- 2023
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9. Inferring direction of associations between histone modifications using a neural processes-based framework
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Ganesan, Ananthakrishnan, Dermadi, Denis, Kalesinskas, Laurynas, Donato, Michele, Sowers, Rosalie, Utz, Paul J., and Khatri, Purvesh
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- 2023
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10. Factors associated with immune responses to SARS-CoV-2 vaccination in autoimmune disease individuals
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Anderson, Erik, primary, Powell, Michael, additional, Yang, Emily, additional, Kar, Ananya, additional, Leung, Tung Ming, additional, Sison, Cristina, additional, Steinberg, Rebecca, additional, Mims, Raven, additional, Choudhury, Ananya, additional, Espinosa, Carlo, additional, Zelmanovich, Joshua, additional, Okoye, Nkemakonam C., additional, Choi, Eun Jung, additional, Marder, Galina, additional, Narain, Sonali, additional, Gregersen, Peter K., additional, Mackay, Meggan, additional, Diamond, Betty, additional, Levy, Todd, additional, Zanos, Theodoros P., additional, Khosroshahi, Arezou, additional, Sanz, Ignacio, additional, Luning Prak, Eline T., additional, Bar-Or, Amit, additional, Merrill, Joan, additional, Arriens, Cristina, additional, Pardo, Gabriel, additional, Guthridge, Joel, additional, James, Judith, additional, Payne, Aimee, additional, Utz, Paul J., additional, Boss, Jeremy M., additional, Aranow, Cynthia, additional, and Davidson, Anne, additional
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- 2024
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11. A GMR-based assay for quantification of the human response to influenza
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Ravi, Neeraja, Chang, Sarah E., Franco, Luis M., Nagamani, Sandesh C.S., Khatri, Purvesh, Utz, Paul J., and Wang, Shan X.
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- 2022
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12. Cytokine signatures differentiate systemic sclerosis patients at high versus low risk for pulmonary arterial hypertension
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Kolstad, Kathleen D., Khatri, Avani, Donato, Michele, Chang, Sarah E., Li, Shufeng, Steen, Virginia D., Utz, Paul J., Khatri, Purvesh, and Chung, Lorinda
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- 2022
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13. IL-12 drives the differentiation of human T follicular regulatory cells.
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Castaño, Diana, Wang, Sidney, Atencio-Garcia, Segovia, Shields, Emily J., Rico, Maria C., Sharpe, Hannah, Bustamante, Jacinta, Feng, Allan, Le Coz, Carole, Romberg, Neil, Tobias, John W., Utz, Paul J., Henrickson, Sarah E., Casanova, Jean-Laurent, Bonasio, Roberto, and Locci, Michela
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T helper cells ,REGULATORY T cells ,B cells ,CELL differentiation ,GENETIC transcription - Abstract
T follicular regulatory (T
fr ) cells can counteract the B cell helper activity of T follicular helper (Tfh ) cells and hinder the production of antibodies against self-antigens or allergens. A mechanistic understanding of the cytokines initiating the differentiation of human regulatory T (Treg ) cells into Tfr cells is still missing. Herein, we report that low doses of the pro-Tfh cytokine interleukin-12 (IL-12) drive the induction of a Tfr cell program on activated human Treg cells while also preserving their regulatory function. Mechanistically, we found that IL-12 led to STAT4 (signal transducer and activator of transcription 4) phosphorylation and binding to IL-12–driven follicular signature genes. Patients with inborn errors of immunity in the IL12RB1 gene presented with a strong decrease in circulating Tfr cells and produced higher levels of anti-actin autoantibodies in vivo. Overall, this study unveils IL-12 as an inducer of Tfr cell differentiation in vivo and provides an approach for the in vitro generation of human Tfr -like cells. Editor's summary: T follicular regulatory (Tfr ) cells balance the activity of T follicular helper cells and suppress B cell responses to self-antigens and allergens. However, the key signals involved in Tfr cell differentiation, particularly in humans, remain incompletely understood. By screening the effects of multiple cytokines on human regulatory T cells, Castaño et al. identified interleukin-12 (IL-12) as the most potent inducer of Tfr cell differentiation in vitro. IL-12 promoted the acquisition of a follicular gene expression program and STAT4 (signal transducer and activator of transcription 4) binding at signature follicular loci. In addition, patients bearing mutations in the IL12RB1 gene displayed a strong decrease in circulating Tfr cells. Together, these findings identify IL-12 as a driver of human Tfr cell differentiation, thus enabling their in vitro generation. —Claire Olingy [ABSTRACT FROM AUTHOR]- Published
- 2024
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14. Author Correction: Systems vaccinology of the BNT162b2 mRNA vaccine in humans
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Arunachalam, Prabhu S., Scott, Madeleine K. D., Hagan, Thomas, Li, Chunfeng, Feng, Yupeng, Wimmers, Florian, Grigoryan, Lilit, Trisal, Meera, Edara, Venkata Viswanadh, Lai, Lilin, Chang, Sarah Esther, Feng, Allan, Dhingra, Shaurya, Shah, Mihir, Lee, Alexandra S., Chinthrajah, Sharon, Sindher, Sayantani B., Mallajosyula, Vamsee, Gao, Fei, Sigal, Natalia, Kowli, Sangeeta, Gupta, Sheena, Pellegrini, Kathryn, Tharp, Gregory, Maysel-Auslender, Sofia, Hamilton, Sydney, Aoued, Hadj, Hrusovsky, Kevin, Roskey, Mark, Bosinger, Steven E., Maecker, Holden T., Boyd, Scott D., Davis, Mark M., Utz, Paul J., Suthar, Mehul S., Khatri, Purvesh, Nadeau, Kari C., and Pulendran, Bali
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- 2023
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15. Methods for high-dimensional analysis of cells dissociated from cryopreserved synovial tissue
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Donlin, Laura T, Rao, Deepak A, Wei, Kevin, Slowikowski, Kamil, McGeachy, Mandy J, Turner, Jason D, Meednu, Nida, Mizoguchi, Fumitaka, Gutierrez-Arcelus, Maria, Lieb, David J, Keegan, Joshua, Muskat, Kaylin, Hillman, Joshua, Rozo, Cristina, Ricker, Edd, Eisenhaure, Thomas M, Li, Shuqiang, Browne, Edward P, Chicoine, Adam, Sutherby, Danielle, Noma, Akiko, Accelerating Medicines Partnership RA/SLE Network, Nusbaum, Chad, Kelly, Stephen, Pernis, Alessandra B, Ivashkiv, Lionel B, Goodman, Susan M, Robinson, William H, Utz, Paul J, Lederer, James A, Gravallese, Ellen M, Boyce, Brendan F, Hacohen, Nir, Pitzalis, Costantino, Gregersen, Peter K, Firestein, Gary S, Raychaudhuri, Soumya, Moreland, Larry W, Holers, V Michael, Bykerk, Vivian P, Filer, Andrew, Boyle, David L, Brenner, Michael B, and Anolik, Jennifer H
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Accelerating Medicines Partnership RA/SLE Network ,Synovial Membrane ,Humans ,Arthritis ,Rheumatoid ,Cryopreservation ,Flow Cytometry ,High-Throughput Screening Assays ,Accelerating Medicines Partnership ,Arthroplasty ,CyTOF ,Mass cytometry ,RNA sequencing ,Rheumatoid arthritis ,Synovial biopsy ,Synovial tissue ,Arthritis ,Autoimmune Disease ,Biotechnology ,Human Genome ,Clinical Research ,Genetics ,Bioengineering ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Arthritis & Rheumatology ,Clinical Sciences ,Immunology ,Public Health and Health Services - Abstract
BackgroundDetailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership RA/SLE Network aims to deconstruct autoimmune pathology by examining cells within target tissues through multiple high-dimensional assays. Robust standardized protocols need to be developed before cellular phenotypes at a single cell level can be effectively compared across patient samples.MethodsMultiple clinical sites collected cryopreserved synovial tissue fragments from arthroplasty and synovial biopsy in a 10% DMSO solution. Mechanical and enzymatic dissociation parameters were optimized for viable cell extraction and surface protein preservation for cell sorting and mass cytometry, as well as for reproducibility in RNA sequencing (RNA-seq). Cryopreserved synovial samples were collectively analyzed at a central processing site by a custom-designed and validated 35-marker mass cytometry panel. In parallel, each sample was flow sorted into fibroblast, T-cell, B-cell, and macrophage suspensions for bulk population RNA-seq and plate-based single-cell CEL-Seq2 RNA-seq.ResultsUpon dissociation, cryopreserved synovial tissue fragments yielded a high frequency of viable cells, comparable to samples undergoing immediate processing. Optimization of synovial tissue dissociation across six clinical collection sites with ~ 30 arthroplasty and ~ 20 biopsy samples yielded a consensus digestion protocol using 100 μg/ml of Liberase™ TL enzyme preparation. This protocol yielded immune and stromal cell lineages with preserved surface markers and minimized variability across replicate RNA-seq transcriptomes. Mass cytometry analysis of cells from cryopreserved synovium distinguished diverse fibroblast phenotypes, distinct populations of memory B cells and antibody-secreting cells, and multiple CD4+ and CD8+ T-cell activation states. Bulk RNA-seq of sorted cell populations demonstrated robust separation of synovial lymphocytes, fibroblasts, and macrophages. Single-cell RNA-seq produced transcriptomes of over 1000 genes/cell, including transcripts encoding characteristic lineage markers identified.ConclusionsWe have established a robust protocol to acquire viable cells from cryopreserved synovial tissue with intact transcriptomes and cell surface phenotypes. A centralized pipeline to generate multiple high-dimensional analyses of synovial tissue samples collected across a collaborative network was developed. Integrated analysis of such datasets from large patient cohorts may help define molecular heterogeneity within RA pathology and identify new therapeutic targets and biomarkers.
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- 2018
16. Impaired innate and adaptive immune responses to BNT162b2 SARS-CoV-2 vaccination in systemic lupus erythematosus
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Sarin, Kavita Y., primary, Zheng, Hong, additional, Chaichian, Yashaar, additional, Arunachalam, Prabhu S., additional, Swaminathan, Gayathri, additional, Eschholz, Alec, additional, Gao, Fei, additional, Wirz, Oliver F., additional, Lam, Brandon, additional, Yang, Emily, additional, Lee, Lori W., additional, Feng, Allan, additional, Lewis, Matthew A., additional, Lin, Janice, additional, Maecker, Holden T., additional, Boyd, Scott D., additional, Davis, Mark M., additional, Nadeau, Kari C., additional, Pulendran, Bali, additional, Khatri, Purvesh, additional, Utz, Paul J., additional, and Zaba, Lisa C., additional
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- 2024
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17. T cell help shapes B cell tolerance
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Akama-Garren, Elliot H., primary, Yin, Xihui, additional, Prestwood, Tyler R., additional, Ma, Minghe, additional, Utz, Paul J., additional, and Carroll, Michael C., additional
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- 2024
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18. The single-cell epigenomic and transcriptional landscape of immunity to influenza vaccination
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Wimmers, Florian, Donato, Michele, Kuo, Alex, Ashuach, Tal, Gupta, Shakti, Li, Chunfeng, Dvorak, Mai, Foecke, Mariko Hinton, Chang, Sarah E., Hagan, Thomas, De Jong, Sanne E., Maecker, Holden T., van der Most, Robbert, Cheung, Peggie, Cortese, Mario, Bosinger, Steven E., Davis, Mark, Rouphael, Nadine, Subramaniam, Shankar, Yosef, Nir, Utz, Paul J., Khatri, Purvesh, and Pulendran, Bali
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- 2021
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19. Systems vaccinology of the BNT162b2 mRNA vaccine in humans
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Arunachalam, Prabhu S., Scott, Madeleine K. D., Hagan, Thomas, Li, Chunfeng, Feng, Yupeng, Wimmers, Florian, Grigoryan, Lilit, Trisal, Meera, Edara, Venkata Viswanadh, Lai, Lilin, Chang, Sarah Esther, Feng, Allan, Dhingra, Shaurya, Shah, Mihir, Lee, Alexandra S., Chinthrajah, Sharon, Sindher, Sayantani B., Mallajosyula, Vamsee, Gao, Fei, Sigal, Natalia, Kowli, Sangeeta, Gupta, Sheena, Pellegrini, Kathryn, Tharp, Gregory, Maysel-Auslender, Sofia, Hamilton, Sydney, Aoued, Hadj, Hrusovsky, Kevin, Roskey, Mark, Bosinger, Steven E., Maecker, Holden T., Boyd, Scott D., Davis, Mark M., Utz, Paul J., Suthar, Mehul S., Khatri, Purvesh, Nadeau, Kari C., and Pulendran, Bali
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- 2021
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20. Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection: The STOP-PASC Randomized Clinical Trial
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Geng, Linda N., Bonilla, Hector, Hedlin, Haley, Jacobson, Karen B., Tian, Lu, Jagannathan, Prasanna, Yang, Phillip C., Subramanian, Aruna K., Liang, Jane W., Shen, Sa, Deng, Yaowei, Shaw, Blake J., Botzheim, Bren, Desai, Manisha, Pathak, Divya, Jazayeri, Yasmin, Thai, Daniel, O’Donnell, Andrew, Mohaptra, Sukanya, Leang, Zenita, Reynolds, Gabriella Z. M., Brooks, Erin F., Bhatt, Ami S., Shafer, Robert W., Miglis, Mitchell G., Quach, Tom, Tiwari, Anushri, Banerjee, Anindita, Lopez, Rene N., De Jesus, Magdia, Charnas, Lawrence R., Utz, Paul J., and Singh, Upinder
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IMPORTANCE: There is an urgent need to identify treatments for postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To assess the efficacy of a 15-day course of nirmatrelvir-ritonavir in reducing the severity of select PASC symptoms. DESIGN, SETTING, AND PARTICIPANTS: This was a 15-week blinded, placebo-controlled, randomized clinical trial conducted from November 2022 to September 2023 at Stanford University (California). The participants were adults with moderate to severe PASC symptoms of 3 months or longer duration. INTERVENTIONS: Participants were randomized 2:1 to treatment with oral nirmatrelvir-ritonavir (NMV/r, 300 mg and 100 mg) or with placebo-ritonavir (PBO/r) twice daily for 15 days. MAIN OUTCOMES AND MEASURES: Primary outcome was a pooled severity of 6 PASC symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms) based on a Likert scale score at 10 weeks. Secondary outcomes included symptom severity at different time points, symptom burden and relief, patient global measures, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, orthostatic vital signs, and sit-to-stand test change from baseline. RESULTS: Of the 155 participants (median [IQR] age, 43 [34-54] years; 92 [59%] females), 102 were randomized to the NMV/r group and 53 to the PBO/r group. Nearly all participants (n = 153) had received the primary series for COVID-19 vaccination. Mean (SD) time between index SARS-CoV-2 infection and randomization was 17.5 (9.1) months. There was no statistically significant difference in the model-derived severity outcome pooled across the 6 core symptoms at 10 weeks between the NMV/r and PBO/r groups. No statistically significant between-group differences were found at 10 weeks in the Patient Global Impression of Severity or Patient Global Impression of Change scores, summative symptom scores, and change from baseline to 10 weeks in PROMIS fatigue, dyspnea, cognitive function, and physical function measures. Adverse event rates were similar in NMV/r and PBO/r groups and mostly of low grade. CONCLUSIONS AND RELEVANCE: The results of this randomized clinical trial showed that a 15-day course of NMV/r in a population of patients with PASC was generally safe but did not demonstrate a significant benefit for improving select PASC symptoms in a mostly vaccinated cohort with protracted symptom duration. Further studies are needed to determine the role of antivirals in the treatment of PASC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05576662
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- 2024
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21. Repression of CTSG, ELANE and PRTN3-mediated histone H3 proteolytic cleavage promotes monocyte-to-macrophage differentiation
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Cheung, Peggie, Schaffert, Steven, Chang, Sarah E., Dvorak, Mai, Donato, Michele, Macaubas, Claudia, Foecke, Mariko H., Li, Tie-Mei, Zhang, Lichao, Coan, John P., Schulert, Grant S., Grom, Alexei A., Henderson, Lauren A., Nigrovic, Peter A., Elias, Joshua E., Gozani, Or, Mellins, Elizabeth D., Khatri, Purvesh, Utz, Paul J., and Kuo, Alex J.
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- 2021
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22. Integrated, multicohort analysis of systemic sclerosis identifies robust transcriptional signature of disease severity.
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Lofgren, Shane, Hinchcliff, Monique, Carns, Mary, Wood, Tammara, Aren, Kathleen, Arroyo, Esperanza, Cheung, Peggie, Kuo, Alex, Valenzuela, Antonia, Haemel, Anna, Wolters, Paul J, Gordon, Jessica, Spiera, Robert, Assassi, Shervin, Boin, Francesco, Chung, Lorinda, Fiorentino, David, Utz, Paul J, Whitfield, Michael L, and Khatri, Purvesh
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Scleroderma ,Autoimmune Disease ,Orphan Drug ,Clinical Research ,Rare Diseases ,Detection ,screening and diagnosis ,4.1 Discovery and preclinical testing of markers and technologies ,Inflammatory and immune system - Abstract
Systemic sclerosis (SSc) is a rare autoimmune disease with the highest case-fatality rate of all connective tissue diseases. Current efforts to determine patient response to a given treatment using the modified Rodnan skin score (mRSS) are complicated by interclinician variability, confounding, and the time required between sequential mRSS measurements to observe meaningful change. There is an unmet critical need for an objective metric of SSc disease severity. Here, we performed an integrated, multicohort analysis of SSc transcriptome data across 7 datasets from 6 centers composed of 515 samples. Using 158 skin samples from SSc patients and healthy controls recruited at 2 centers as a discovery cohort, we identified a 415-gene expression signature specific for SSc, and validated its ability to distinguish SSc patients from healthy controls in an additional 357 skin samples from 5 independent cohorts. Next, we defined the SSc skin severity score (4S). In every SSc cohort of skin biopsy samples analyzed in our study, 4S correlated significantly with mRSS, allowing objective quantification of SSc disease severity. Using transcriptome data from the largest longitudinal trial of SSc patients to date, we showed that 4S allowed us to objectively monitor individual SSc patients over time, as (a) the change in 4S of a patient is significantly correlated with change in the mRSS, and (b) the change in 4S at 12 months of treatment could predict the change in mRSS at 24 months. Our results suggest that 4S could be used to distinguish treatment responders from nonresponders prior to mRSS change. Our results demonstrate the potential clinical utility of a novel robust molecular signature and a computational approach to SSc disease severity quantification.
- Published
- 2016
23. Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus.
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Lee, Jung-Rok, Haddon, D James, Wand, Hannah E, Price, Jordan V, Diep, Vivian K, Hall, Drew A, Petri, Michelle, Baechler, Emily C, Balboni, Imelda M, Utz, Paul J, and Wang, Shan X
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Humans ,Lupus Erythematosus ,Systemic ,Ribonucleoprotein ,U1 Small Nuclear ,Interferons ,Autoantibodies ,Immunoassay ,Protein Array Analysis ,Molecular Diagnostic Techniques ,Sensitivity and Specificity ,Case-Control Studies ,Biosensing Techniques ,Lupus Erythematosus ,Systemic ,Ribonucleoprotein ,U1 Small Nuclear - Abstract
High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice.
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- 2016
24. Epigenetic Profiling of PTPN11 Mutant JMML Hematopoietic Stem and Progenitor Cells Reveals an Aberrant Histone Landscape
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Sinha, Roshani, primary, Dvorak, Mai, additional, Ganesan, Ananthakrishnan, additional, Kalesinskas, Larry, additional, Niemeyer, Charlotte M., additional, Flotho, Christian, additional, Sakamoto, Kathleen M., additional, Lacayo, Norman, additional, Patil, Rachana Vinay, additional, Perriman, Rhonda, additional, Cepika, Alma-Martina, additional, Liu, Yunying Lucy, additional, Kuo, Alex, additional, Utz, Paul J., additional, Khatri, Purvesh, additional, and Bertaina, Alice, additional
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- 2023
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25. 5.44 Antidopamine Receptor Autoantibody Detection in Postinfectious Neuropsychiatric Syndromes
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Yin, Xihui, primary, Prestwood, Tyler, additional, Utz, Paul J., additional, and Frankovich, Jennifer, additional
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- 2023
- Full Text
- View/download PDF
26. Broad-spectrum antibodies against self-antigens and cytokines in RAG deficiency.
- Author
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Walter, Jolan E, Rosen, Lindsey B, Csomos, Krisztian, Rosenberg, Jacob M, Mathew, Divij, Keszei, Marton, Ujhazi, Boglarka, Chen, Karin, Lee, Yu Nee, Tirosh, Irit, Dobbs, Kerry, Al-Herz, Waleed, Cowan, Morton J, Puck, Jennifer, Bleesing, Jack J, Grimley, Michael S, Malech, Harry, De Ravin, Suk See, Gennery, Andrew R, Abraham, Roshini S, Joshi, Avni Y, Boyce, Thomas G, Butte, Manish J, Nadeau, Kari C, Balboni, Imelda, Sullivan, Kathleen E, Akhter, Javeed, Adeli, Mehdi, El-Feky, Reem A, El-Ghoneimy, Dalia H, Dbaibo, Ghassan, Wakim, Rima, Azzari, Chiara, Palma, Paolo, Cancrini, Caterina, Capuder, Kelly, Condino-Neto, Antonio, Costa-Carvalho, Beatriz T, Oliveira, Joao Bosco, Roifman, Chaim, Buchbinder, David, Kumanovics, Attila, Franco, Jose Luis, Niehues, Tim, Schuetz, Catharina, Kuijpers, Taco, Yee, Christina, Chou, Janet, Masaad, Michel J, Geha, Raif, Uzel, Gulbu, Gelman, Rebecca, Holland, Steven M, Recher, Mike, Utz, Paul J, Browne, Sarah K, and Notarangelo, Luigi D
- Subjects
Animals ,Mice ,Inbred Strains ,Humans ,Mice ,Virus Diseases ,Granulomatous Disease ,Chronic ,Severe Combined Immunodeficiency ,Autoimmune Diseases ,Disease Models ,Animal ,DNA-Binding Proteins ,Homeodomain Proteins ,Nuclear Proteins ,Autoantibodies ,Autoantigens ,Cytokines ,Antibody Specificity ,Adolescent ,Adult ,Child ,Child ,Preschool ,Infant ,Female ,Male ,Toll-Like Receptors ,DEAD-box RNA Helicases ,Young Adult ,Antibodies ,Neutralizing ,Interferon-Induced Helicase ,IFIH1 ,Autoimmune Disease ,Genetics ,Biotechnology ,Infectious Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Medical and Health Sciences ,Immunology - Abstract
Patients with mutations of the recombination-activating genes (RAG) present with diverse clinical phenotypes, including severe combined immune deficiency (SCID), autoimmunity, and inflammation. However, the incidence and extent of immune dysregulation in RAG-dependent immunodeficiency have not been studied in detail. Here, we have demonstrated that patients with hypomorphic RAG mutations, especially those with delayed-onset combined immune deficiency and granulomatous/autoimmune manifestations (CID-G/AI), produce a broad spectrum of autoantibodies. Neutralizing anti-IFN-α or anti-IFN-ω antibodies were present at detectable levels in patients with CID-G/AI who had a history of severe viral infections. As this autoantibody profile is not observed in a wide range of other primary immunodeficiencies, we hypothesized that recurrent or chronic viral infections may precipitate or aggravate immune dysregulation in RAG-deficient hosts. We repeatedly challenged Rag1S723C/S723C mice, which serve as a model of leaky SCID, with agonists of the virus-recognizing receptors TLR3/MDA5, TLR7/-8, and TLR9 and found that this treatment elicits autoantibody production. Altogether, our data demonstrate that immune dysregulation is an integral aspect of RAG-associated immunodeficiency and indicate that environmental triggers may modulate the phenotypic expression of autoimmune manifestations.
- Published
- 2015
27. New-onset IgG autoantibodies in hospitalized patients with COVID-19
- Author
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Chang, Sarah Esther, Feng, Allan, Meng, Wenzhao, Apostolidis, Sokratis A., Mack, Elisabeth, Artandi, Maja, Barman, Linda, Bennett, Kate, Chakraborty, Saborni, Chang, Iris, Cheung, Peggie, Chinthrajah, Sharon, Dhingra, Shaurya, Do, Evan, Finck, Amanda, Gaano, Andrew, Geßner, Reinhard, Giannini, Heather M., Gonzalez, Joyce, Greib, Sarah, Gündisch, Margrit, Hsu, Alex Ren, Kuo, Alex, Manohar, Monali, Mao, Rong, Neeli, Indira, Neubauer, Andreas, Oniyide, Oluwatosin, Powell, Abigail E., Puri, Rajan, Renz, Harald, Schapiro, Jeffrey, Weidenbacher, Payton A., Wittman, Richard, Ahuja, Neera, Chung, Ho-Ryun, Jagannathan, Prasanna, James, Judith A., Kim, Peter S., Meyer, Nuala J., Nadeau, Kari C., Radic, Marko, Robinson, William H., Singh, Upinder, Wang, Taia T., Wherry, E. John, Skevaki, Chrysanthi, Luning Prak, Eline T., and Utz, Paul J.
- Published
- 2021
- Full Text
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28. Tetramers reveal IL-17–secreting CD4+ T cells that are specific for U1-70 in lupus and mixed connective tissue disease
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Kattah, Nicole H, Newell, Evan W, Jarrell, Justin Ansel, Chu, Alvina D, Xie, Jianming, Kattah, Michael G, Goldberger, Ofir, Ye, Jessica, Chakravarty, Eliza F, Davis, Mark M, and Utz, Paul J
- Subjects
Lupus ,Autoimmune Disease ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Animals ,Autoantibodies ,CD4-Positive T-Lymphocytes ,Enzyme-Linked Immunosorbent Assay ,Female ,Humans ,Interleukin-17 ,Lupus Erythematosus ,Systemic ,Male ,Mice ,Mixed Connective Tissue Disease ,Oligopeptides ,Phosphorylation ,tetramer ,autoimmunity ,lupus ,SLE ,IL-17 - Abstract
Antigen-specific CD4(+) T cells are implicated in the autoimmune disease systemic lupus erythematosus (SLE), but little is known about the peptide antigens that they recognize and their precise function in disease. We generated a series of MHC class II tetramers of I-E(k)-containing peptides from the spliceosomal protein U1-70 that specifically stain distinct CD4(+) T-cell populations in MRL/lpr mice. The T-cell populations recognize an epitope differing only by the presence or absence of a single phosphate residue at position serine(140). The frequency of CD4(+) T cells specific for U1-70(131-150):I-E(k) (without phosphorylation) correlates with disease severity and anti-U1-70 autoantibody production. These T cells also express RORγt and produce IL-17A. Furthermore, the U1-70-specific CD4(+) T cells that produce IL-17A are detected in a subset of patients with SLE and are significantly increased in patients with mixed connective tissue disease. These studies provide tools for studying antigen-specific CD4(+) T cells in lupus, and demonstrate an antigen-specific source of IL-17A in autoimmune disease.
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- 2015
29. Quantification of cDNA on GMR biosensor array towards point-of-care gene expression analysis
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Ravi, Neeraja, Rizzi, Giovanni, Chang, Sarah E., Cheung, Peggie, Utz, Paul J., and Wang, Shan X.
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- 2019
- Full Text
- View/download PDF
30. Single-cell epigenetics – Chromatin modification atlas unveiled by mass cytometry
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Cheung, Peggie, Vallania, Francesco, Dvorak, Mai, Chang, Sarah E., Schaffert, Steven, Donato, Michele, Rao, Aditya M., Mao, Rong, Utz, Paul J., Khatri, Purvesh, and Kuo, Alex J.
- Published
- 2018
- Full Text
- View/download PDF
31. Endothelial Biomarkers of Systemic Sclerosis‐Associated Pulmonary Hypertension
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Lammi, Matthew R., primary, Kolstad, Kathleen D., additional, Saketkoo, Lesley Ann, additional, Khatri, Avani, additional, Utz, Paul J., additional, Steen, Virginia D., additional, and Chung, Lorinda, additional
- Published
- 2023
- Full Text
- View/download PDF
32. Ancestry-based differences in the immune phenotype are associated with lupus activity
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Slight-Webb, Samantha, primary, Thomas, Kevin, additional, Smith, Miles, additional, Wagner, Catriona A., additional, Macwana, Susan, additional, Bylinska, Aleksandra, additional, Donato, Michele, additional, Dvorak, Mai, additional, Chang, Sarah E., additional, Kuo, Alex, additional, Cheung, Peggie, additional, Kalesinskas, Laurynas, additional, Ganesan, Ananthakrishnan, additional, Dermadi, Denis, additional, Guthridge, Carla J., additional, DeJager, Wade, additional, Wright, Christian, additional, Foecke, Mariko H., additional, Merrill, Joan T., additional, Chakravarty, Eliza, additional, Arriens, Cristina, additional, Maecker, Holden T., additional, Khatri, Purvesh, additional, Utz, Paul J., additional, James, Judith A., additional, and Guthridge, Joel M., additional
- Published
- 2023
- Full Text
- View/download PDF
33. Activation of Autoreactive Lymphocytes in the Lung by STING Gain-of-function Mutation Radioresistant Cells
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Gao, Kevin MingJie, primary, Nündel, Kerstin, additional, Chiang, Kristy, additional, Yin, Xihui, additional, Utz, Paul J., additional, Fitzgerald, Kate, additional, and Marshak-Rothstein, Ann, additional
- Published
- 2023
- Full Text
- View/download PDF
34. Protein Microarrays with Carbon Nanotubes as Multi-Color Raman Labels
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Chen, Zhuo, Tabakman, Scott M., Goodwin, Andrew P., Kattah, Michael G., Daranciang, Dan, Wang, Xinran, Zhang, Guangyu, Li, Xiaolin, Liu, Zhuang, Utz, Paul J., Jiang, Kaili, Fan, Shoushan, and Dai, Hongjie
- Subjects
Condensed Matter - Materials Science - Abstract
Detection of biomolecules is important in proteomics and clinical diagnosis and treatment of diseases. Here, we apply functionalized, macromolecular, single walled carbon nanotubes SWNTs as multi-color Raman labels to protein arrays for highly sensitive, multiplexed protein detection. Raman detection utilizes the sharp peaks of SWNTs with minimal background interference, affording a high signal to noise ratio needed for ultra-sensitive detection. Surface-enhanced Raman scattering SERS combined with the strong resonance Raman intensity of SWNTs, affords detection sensitivity down to 1 fM, a three order of magnitude improvement over most of reported fluorescence-based protein detections. We show that human autoantibodies to Proteinase 3 aPR3, a biomarker for the autoimmune disease Wegeners granulomatosis, is detected by Raman in human serum up to a 107 dilution. Moreover, SWNT Raman tags are stable against photobleaching and quenching, and by conjugating different antibodies to pure 12C and 13C SWNT isotopes, we demonstrate two-color SWNT Raman-based protein detection in a multiplexed fashion., Comment: Nature Biotechnology, in press
- Published
- 2008
35. Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus.
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Price, Jordan V, Haddon, David J, Kemmer, Dodge, Delepine, Guillaume, Mandelbaum, Gil, Jarrell, Justin A, Gupta, Rohit, Balboni, Imelda, Chakravarty, Eliza F, Sokolove, Jeremy, Shum, Anthony K, Anderson, Mark S, Cheng, Mickie H, Robinson, William H, Browne, Sarah K, Holland, Steven M, Baechler, Emily C, and Utz, Paul J
- Subjects
Animals ,Humans ,Mice ,Mycobacterium Infections ,Lupus Erythematosus ,Systemic ,Polyendocrinopathies ,Autoimmune ,Inflammation ,Immunoglobulin G ,Interferon-alpha ,Recombinant Proteins ,Autoantibodies ,Autoantigens ,Cytokines ,Protein Array Analysis ,Antibody Specificity ,B-Cell Activating Factor ,Autoimmune Disease ,Lupus ,Biotechnology ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Medical and Health Sciences ,Immunology - Abstract
Autoantibodies against cytokines, chemokines, and growth factors inhibit normal immunity and are implicated in inflammatory autoimmune disease and diseases of immune deficiency. In an effort to evaluate serum from autoimmune and immunodeficient patients for Abs against cytokines, chemokines, and growth factors in a high-throughput and unbiased manner, we constructed a multiplex protein microarray for detection of serum factor-binding Abs and used the microarray to detect autoantibody targets in SLE. We designed a nitrocellulose-surface microarray containing human cytokines, chemokines, and other circulating proteins and demonstrated that the array permitted specific detection of serum factor-binding probes. We used the arrays to detect previously described autoantibodies against cytokines in samples from individuals with autoimmune polyendocrine syndrome type 1 and chronic mycobacterial infection. Serum profiling from individuals with SLE revealed that among several targets, elevated IgG autoantibody reactivity to B cell-activating factor (BAFF) was associated with SLE compared with control samples. BAFF reactivity correlated with the severity of disease-associated features, including IFN-α-driven SLE pathology. Our results showed that serum factor protein microarrays facilitate detection of autoantibody reactivity to serum factors in human samples and that BAFF-reactive autoantibodies may be associated with an elevated inflammatory disease state within the spectrum of SLE.
- Published
- 2013
36. Distinct phenotype of CD4+ T cells driving celiac disease identified in multiple autoimmune conditions
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Christophersen, Asbjørn, Lund, Eivind G., Snir, Omri, Solà, Elsa, Kanduri, Chakravarthi, Dahal-Koirala, Shiva, Zühlke, Stephanie, Molberg, Øyvind, Utz, Paul J., Rohani-Pichavant, Mina, Simard, Julia F., Dekker, Cornelia L., Lundin, Knut E. A., Sollid, Ludvig M., and Davis, Mark M.
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- 2019
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- View/download PDF
37. The intersection of COVID-19 and autoimmunity
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Knight, Jason S., Caricchio, Roberto, Casanova, Jean-Laurent, Combes, Alexis J., Diamond, Betty, Fox, Sharon E., Hanauer, David A., James, Judith A., Kanthi, Yogendra, Ladd, Virginia, Mehta, Puja, Ring, Aaron M., Sanz, Ignacio, Selmi, Carlo, Tracy, Russell P., Utz, Paul J., Wagner, Catriona A., Wang, Julia Y., and McCune, William J.
- Subjects
Medical research ,Medicine, Experimental ,Autoimmunity -- Physiological aspects ,Host-virus relationships ,Health care industry - Abstract
Acute COVID-19, caused by SARS-CoV-2, is characterized by diverse clinical presentations, ranging from asymptomatic infection to fatal respiratory failure, and often associated with varied longer- term sequelae. Over the past 18 months, it has become apparent that inappropriate immune responses contribute to the pathogenesis of severe COVID-19. Researchers working at the intersection of COVID-19 and autoimmunity recently gathered at an American Autoimmune Related Diseases Association Noel R. Rose Colloquium to address the current state of knowledge regarding two important questions: Does established autoimmunity predispose to severe COVID-19? And, at the same time, can SARS-CoV-2 infection trigger de novo autoimmunity? Indeed, work to date has demonstrated that 10% to 15% of patients with critical COVID-19 pneumonia exhibit autoantibodies against type I interferons, suggesting that preexisting autoimmunity underlies severe disease in some patients. Other studies have identified functional autoantibodies following infection with SARS-CoV-2, such as those that promote thrombosis or antagonize cytokine signaling. These autoantibodies may arise from a predominantly extrafollicular B cell response that is more prone to generating autoantibody-secreting B cells. This Review highlights the current understanding, evolving concepts, and unanswered questions provided by this unique opportunity to determine mechanisms by which a viral infection can be exacerbated by, and even trigger, autoimmunity. The potential role of autoimmunity in postacute sequelae of COVID-19 is also discussed., Introduction In December 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, Hubei Province, China, and caused the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 presentations [...]
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- 2021
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38. Addendum: Systems vaccinology of the BNT162b2 mRNA vaccine in humans
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Arunachalam, Prabhu S., primary, Scott, Madeleine K. D., additional, Hagan, Thomas, additional, Li, Chunfeng, additional, Feng, Yupeng, additional, Wimmers, Florian, additional, Grigoryan, Lilit, additional, Trisal, Meera, additional, Edara, Venkata Viswanadh, additional, Lai, Lilin, additional, Chang, Sarah Esther, additional, Feng, Allan, additional, Dhingra, Shaurya, additional, Shah, Mihir, additional, Lee, Alexandra S., additional, Chinthrajah, Sharon, additional, Sindher, Sayantani B., additional, Mallajosyula, Vamsee, additional, Gao, Fei, additional, Sigal, Natalia, additional, Kowli, Sangeeta, additional, Gupta, Sheena, additional, Pellegrini, Kathryn, additional, Tharp, Gregory, additional, Maysel-Auslender, Sofia, additional, Hamilton, Sydney, additional, Aoued, Hadj, additional, Hrusovsky, Kevin, additional, Roskey, Mark, additional, Bosinger, Steven E., additional, Maecker, Holden T., additional, Boyd, Scott D., additional, Davis, Mark M., additional, Utz, Paul J., additional, Suthar, Mehul S., additional, Khatri, Purvesh, additional, Nadeau, Kari C., additional, and Pulendran, Bali, additional
- Published
- 2023
- Full Text
- View/download PDF
39. Noncovalent Functionalization of Carbon Nanotubes for Highly Specific Electronic Biosensors
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Chen, Robert J., Bangsaruntip, Sarunya, Drouvalakis, Katerina A., Shim, Moonsub, Li, Yiming, Kim, Woong, Utz, Paul J., and Dai, Hongjie
- Published
- 2003
40. Expression-based Pathway Signature Analysis (EPSA): Mining publicly available microarray data for insight into human disease
- Author
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Tenenbaum, Jessica D, Walker, Michael G, Utz, Paul J, and Butte, Atul J
- Subjects
Biological Sciences ,Bioinformatics and Computational Biology ,Cancer ,Genetics ,Biotechnology ,Human Genome ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,Medical Biochemistry and Metabolomics ,Oncology and Carcinogenesis ,Genetics & Heredity ,Medical biochemistry and metabolomics - Abstract
BackgroundPublicly available data repositories facilitate the sharing of an ever-increasing amount of microarray data. However, these datasets remain highly underutilized. Reutilizing the data could offer insights into questions and diseases entirely distinct from those considered in the original experimental design.MethodsWe first analyzed microarray datasets derived from known perturbations of specific pathways using the samr package in R to identify specific patterns of change in gene expression. We refer to these pattern of gene expression alteration as a "pathway signatures." We then used Spearman's rank correlation coefficient, a non-parametric measure of correlation, to determine similarities between pathway signatures and disease profiles, and permutation analysis to evaluate false discovery rate. This enabled detection of statistically significant similarity between these pathway signatures and corresponding changes observed in human disease. Finally, we evaluated pathway activation, as indicated by correlation with the pathway signature, as a risk factor for poor prognosis using multiple unrelated, publicly available datasets.ResultsWe have developed a novel method, Expression-based Pathway Signature Analysis (EPSA). We demonstrate that ESPA is a rigorous computational approach for statistically evaluating the degree of similarity between highly disparate sources of microarray expression data. We also show how EPSA can be used in a number of cases to stratify patients with differential disease prognosis. EPSA can be applied to many different types of datasets in spite of different platforms, different experimental designs, and different species. Applying this method can yield new insights into human disease progression.ConclusionEPSA enables the use of publicly available data for an entirely new, translational purpose to enable the identification of potential pathways of dysregulation in human disease, as well as potential leads for therapeutic molecular targets.
- Published
- 2008
41. Smith-Magenis Syndrome Patients Often Display Antibody Deficiency but Not Other Immune Pathologies
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Perkins, Tiffany, Rosenberg, Jacob M., Le Coz, Carole, Alaimo, Joseph T., Trofa, Melissa, Mullegama, Sureni V., Antaya, Richard J., Jyonouchi, Soma, Elsea, Sarah H., Utz, Paul J., Meffre, Eric, and Romberg, Neil
- Published
- 2017
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42. Stanford University School of Medicine
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Bernstein, Daniel, Irvine, Cynthia A., Basaviah, Preetha, Lau, James N., Austin, Bahij, Utz, Paul J., and Gesundheit, Neil
- Published
- 2020
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- View/download PDF
43. Portable, one-step, and rapid GMR biosensor platform with smartphone interface
- Author
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Choi, Joohong, Gani, Adi Wijaya, Bechstein, Daniel J.B., Lee, Jung-Rok, Utz, Paul J., and Wang, Shan X.
- Published
- 2016
- Full Text
- View/download PDF
44. Innovations in MD-only physician-scientist training: experiences from the Burroughs Wellcome Fund physician-scientist institutional award initiative
- Author
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McElvaine, Allison T., Hawkins-Salsbury, Jacqueline A., Arora, Vineet M., Gladwin, Mark T., Goldenring, James R., Huston, David P., Krakow, Deborah, Rhee, Kyu, Solway, Julian, Steinman, Richard A., Towler, Dwight A., Utz, Paul J., Yokoyama, Wayne M., Simpson, Rolly L., Muglia, Louis J., Permar, Sallie R., and Gbadegesin, Rasheed A.
- Subjects
Medical research -- Management -- Training ,Medicine, Experimental -- Management -- Training ,Continuing medical education -- Curricula ,Physicians -- Training ,Medical colleges -- Finance ,Medical scientists -- Training ,Company business management ,Company financing ,Health care industry - Abstract
Introduction In the first half of the 20th century, while the value of translating scientific discovery to clinical care was clearly established, the pace of innovation was resulting in increased [...]
- Published
- 2021
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- View/download PDF
45. Data from Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape
- Author
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Woo, Seng-Ryong, primary, Turnis, Meghan E., primary, Goldberg, Monica V., primary, Bankoti, Jaishree, primary, Selby, Mark, primary, Nirschl, Christopher J., primary, Bettini, Matthew L., primary, Gravano, David M., primary, Vogel, Peter, primary, Liu, Chih Long, primary, Tangsombatvisit, Stephanie, primary, Grosso, Joseph F., primary, Netto, George, primary, Smeltzer, Matthew P., primary, Chaux, Alcides, primary, Utz, Paul J., primary, Workman, Creg J., primary, Pardoll, Drew M., primary, Korman, Alan J., primary, Drake, Charles G., primary, and Vignali, Dario A.A., primary
- Published
- 2023
- Full Text
- View/download PDF
46. Supplementary Tables 1-2, Figures 1-11 from Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape
- Author
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Woo, Seng-Ryong, primary, Turnis, Meghan E., primary, Goldberg, Monica V., primary, Bankoti, Jaishree, primary, Selby, Mark, primary, Nirschl, Christopher J., primary, Bettini, Matthew L., primary, Gravano, David M., primary, Vogel, Peter, primary, Liu, Chih Long, primary, Tangsombatvisit, Stephanie, primary, Grosso, Joseph F., primary, Netto, George, primary, Smeltzer, Matthew P., primary, Chaux, Alcides, primary, Utz, Paul J., primary, Workman, Creg J., primary, Pardoll, Drew M., primary, Korman, Alan J., primary, Drake, Charles G., primary, and Vignali, Dario A.A., primary
- Published
- 2023
- Full Text
- View/download PDF
47. Climate change and public health
- Author
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Lee, Alexandra S, primary, Aguilera, Juan, additional, Efobi, Jo Ann, additional, Jung, Youn Soo, additional, Seastedt, Hana, additional, Shah, Mihir M, additional, Yang, Emily, additional, Konvinse, Katherine, additional, Utz, Paul J, additional, Sampath, Vanitha, additional, and Nadeau, Kari C, additional
- Published
- 2023
- Full Text
- View/download PDF
48. Autoantibodies are highly prevalent in non–SARS-CoV-2 respiratory infections and critical illness
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Feng, Allan, primary, Yang, Emily Y., additional, Moore, Andrew Reese, additional, Dhingra, Shaurya, additional, Chang, Sarah Esther, additional, Yin, Xihui, additional, Pi, Ruoxi, additional, Mack, Elisabeth K.M., additional, Völkel, Sara, additional, Geßner, Reinhard, additional, Gündisch, Margrit, additional, Neubauer, Andreas, additional, Renz, Harald, additional, Tsiodras, Sotirios, additional, Fragkou, Paraskevi C., additional, Asuni, Adijat A., additional, Levitt, Joseph E., additional, Wilson, Jennifer G., additional, Leong, Michelle, additional, Lumb, Jennifer H., additional, Mao, Rong, additional, Pinedo, Kassandra, additional, Roque, Jonasel, additional, Richards, Christopher M., additional, Stabile, Mikayla, additional, Swaminathan, Gayathri, additional, Salagianni, Maria L., additional, Triantafyllia, Vasiliki, additional, Bertrams, Wilhelm, additional, Blish, Catherine A., additional, Carette, Jan E., additional, Frankovich, Jennifer, additional, Meffre, Eric, additional, Nadeau, Kari Christine, additional, Singh, Upinder, additional, Wang, Taia T., additional, Luning Prak, Eline T., additional, Herold, Susanne, additional, Andreakos, Evangelos, additional, Schmeck, Bernd, additional, Skevaki, Chrysanthi, additional, Rogers, Angela J., additional, and Utz, Paul J., additional
- Published
- 2023
- Full Text
- View/download PDF
49. Systems biological assessment of the temporal dynamics of immunity to a viral infection in the first weeks and months of life
- Author
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Wimmers, Florian, primary, Burrell, Allison R., additional, Feng, Yupeng, additional, Zheng, Hong, additional, Arunachalam, Prabhu S., additional, Hu, Mengyun, additional, Spranger, Sara, additional, Nyhoff, Lindsay, additional, Joshi, Devyani, additional, Trisal, Meera, additional, Awasthi, Mayanka, additional, Bellusci, Lorenza, additional, Ashraf, Usama, additional, Kowli, Sangeeta, additional, Konvinse, Katherine C., additional, Yang, Emily, additional, Blanco, Michael, additional, Pellegrini, Kathryn, additional, Tharp, Gregory, additional, Hagan, Thomas, additional, Chinthrajah, R. Sharon, additional, Grifoni, Alba, additional, Sette, Alessandro, additional, Nadeau, Kari C., additional, Haslam, David B., additional, Bosinger, Steven E., additional, Wrammert, Jens, additional, Maecker, Holden T., additional, Utz, Paul J., additional, Wang, Taia T., additional, Khurana, Surender, additional, Khatri, Purvesh, additional, Staat, Mary A., additional, and Pulendran, Bali, additional
- Published
- 2023
- Full Text
- View/download PDF
50. Characterising the autoantibody repertoire in systemic sclerosis following myeloablative haematopoietic stem cell transplantation
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Ayoglu, Burcu, primary, Donato, Michele, additional, Furst, Daniel E, additional, Crofford, Leslie J, additional, Goldmuntz, Ellen, additional, Keyes-Elstein, Lynette, additional, James, Judith, additional, Macwana, Susan, additional, Mayes, Maureen D, additional, McSweeney, Peter, additional, Nash, Richard A, additional, Sullivan, Keith M, additional, Welch, Beverly, additional, Pinckney, Ashley, additional, Mao, Rong, additional, Chung, Lorinda, additional, Khatri, Purvesh, additional, and Utz, Paul J, additional
- Published
- 2023
- Full Text
- View/download PDF
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