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10 results on '"Speake, Cate"'

1. Proinflammatory islet antigen reactive CD4 T cells are linked with response to alefacept in type 1 diabetes

Author

Balmas, Elisa, primary, Chen, Janice, additional, Hu, Alex K., additional, DeBerg, Hannah A., additional, Rosasco, Mario G., additional, Gersuk, Vivian H., additional, Serti, Elisavet, additional, Speake, Cate, additional, Greenbaum, Carla J., additional, Nepom, Gerald T., additional, Linsley, Peter S., additional, and Cerosaletti, Karen, additional

Published
2023
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2. IL-6–targeted therapies to block the cytokine or its receptor drive distinct alterations in T cell function

Author

Speake, Cate, primary, Habib, Tania, additional, Lambert, Katharina, additional, Hundhausen, Christian, additional, Lord, Sandra, additional, Dufort, Matthew J., additional, Skinner, Samuel O., additional, Hu, Alex, additional, Kinsman, MacKenzie, additional, Jones, Britta E., additional, Maerz, Megan D., additional, Tatum, Megan, additional, Hocking, Anne M., additional, Nepom, Gerald T., additional, Greenbaum, Carla J., additional, and Buckner, Jane H., additional

Published
2022
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3. Autoreactive T cell receptors with shared germline-like α chains in type 1 diabetes

Author

Linsley, Peter S., primary, Barahmand-pour-Whitman, Fariba, additional, Balmas, Elisa, additional, DeBerg, Hannah A., additional, Flynn, Kaitlin J., additional, Hu, Alex K., additional, Rosasco, Mario G., additional, Chen, Janice, additional, O’Rourke, Colin, additional, Serti, Elisavet, additional, Gersuk, Vivian H., additional, Motwani, Keshav, additional, Seay, Howard R., additional, Brusko, Todd M., additional, Kwok, William W., additional, Speake, Cate, additional, Greenbaum, Carla J., additional, Nepom, Gerald T., additional, and Cerosaletti, Karen, additional

Published
2021
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4. Multiplexing DNA methylation markers to detect circulating cell-free DNA derived from human pancreatic β cells

Author

Neiman, Daniel, primary, Gillis, David, additional, Piyanzin, Sheina, additional, Cohen, Daniel, additional, Fridlich, Ori, additional, Moss, Joshua, additional, Zick, Aviad, additional, Oron, Tal, additional, Sundberg, Frida, additional, Forsander, Gun, additional, Skog, Oskar, additional, Korsgren, Olle, additional, Levy-Khademi, Floris, additional, Arbel, Dan, additional, Hashavia, Saar, additional, Shapiro, A.M. James, additional, Speake, Cate, additional, Greenbaum, Carla, additional, Hosford, Jennifer, additional, Posgai, Amanda, additional, Atkinson, Mark A., additional, Glaser, Benjamin, additional, Schatz, Desmond A., additional, Shemer, Ruth, additional, and Dor, Yuval, additional

Published
2020
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5. A composite immune signature parallels disease progression across T1D subjects

Author

Speake, Cate, primary, Skinner, Samuel O., additional, Berel, Dror, additional, Whalen, Elizabeth, additional, Dufort, Matthew J., additional, Young, William Chad, additional, Odegard, Jared M., additional, Pesenacker, Anne M., additional, Gorus, Frans K., additional, James, Eddie A., additional, Levings, Megan K., additional, Linsley, Peter S., additional, Akirav, Eitan M., additional, Pugliese, Alberto, additional, Hessner, Martin J., additional, Nepom, Gerald T., additional, Gottardo, Raphael, additional, and Long, S. Alice, additional

Published
2019
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8. Treg gene signatures predict and measure type 1 diabetes trajectory

Author

Pesenacker, Anne M., primary, Chen, Virginia, additional, Gillies, Jana, additional, Speake, Cate, additional, Marwaha, Ashish K., additional, Sun, Annika C., additional, Chow, Samuel, additional, Tan, Rusung, additional, Elliott, Thomas, additional, Dutz, Jan P., additional, Tebbutt, Scott J., additional, and Levings, Megan K., additional

Published
2019
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9. Islet-autoreactive CD4+ T cells are linked with response to alefacept in type 1 diabetes.

Author

Balmas E, Chen J, Hu AK, DeBerg HA, Rosasco MG, Gersuk VH, Serti E, Speake C, Greenbaum CJ, Nepom GT, Linsley PS, and Cerosaletti K

Subjects
Humans, CD4-Positive T-Lymphocytes metabolism, Alefacept therapeutic use, C-Peptide, Leukocytes, Mononuclear metabolism, Biomarkers, Receptors, Antigen, T-Cell therapeutic use, Diabetes Mellitus, Type 1 drug therapy, Diabetes Mellitus, Type 1 metabolism
Abstract

Variation in the preservation of β cell function in clinical trials in type 1 diabetes (T1D) has emphasized the need to define biomarkers to predict treatment response. The T1DAL trial targeted T cells with alefacept (LFA-3-Ig) and demonstrated C-peptide preservation in approximately 30% of new-onset T1D individuals. We analyzed islet antigen-reactive (IAR) CD4+ T cells in PBMC samples collected prior to treatment from alefacept- and placebo-treated individuals using flow cytometry and single-cell RNA sequencing. IAR CD4+ T cells at baseline had heterogeneous phenotypes. Transcript profiles formed phenotypic clusters of cells along a trajectory based on increasing maturation and activation, and T cell receptor (TCR) chains showed clonal expansion. Notably, the frequency of IAR CD4+ T cells with a memory phenotype and a unique transcript profile (cluster 3) were inversely correlated with C-peptide preservation in alefacept-treated, but not placebo-treated, individuals. Cluster 3 cells had a proinflammatory phenotype characterized by expression of the transcription factor BHLHE40 and the cytokines GM-CSF and TNF-α, and shared TCR chains with effector memory-like clusters. Our results suggest IAR CD4+ T cells as a potential baseline biomarker of response to therapies targeting the CD2 pathway and warrant investigation for other T cell-related therapies.

Published
2023
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10. Diminished responses to mRNA-based SARS-CoV-2 vaccines in individuals with rheumatoid arthritis on immune-modifying therapies.

Author

Klebanoff SD, Rodda LB, Morishima C, Wener MH, Yuzefpolskiy Y, Bettelli E, Buckner JH, Speake C, Pepper M, and Campbell DJ

Subjects
Humans, COVID-19 Vaccines, SARS-CoV-2, Antibodies, Viral, RNA, Messenger, COVID-19 prevention & control, Arthritis, Rheumatoid drug therapy
Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that causes debilitating swelling and destruction of the joints. People with RA are treated with drugs that actively suppress one or more parts of their immune system, and these may alter the response to vaccination against SARS-CoV-2. In this study, we analyzed blood samples from a cohort of patients with RA after receiving a 2-dose mRNA COVID-19 vaccine regimen. Our data show that individuals on the cytotoxic T lymphocyte antigen 4-Ig therapy abatacept had reduced levels of SARS-CoV-2-neutralizing antibodies after vaccination. At the cellular level, these patients showed reduced activation and class switching of SARS-CoV-2-specific B cells, as well as reduced numbers and impaired helper cytokine production by SARS-CoV-2-specific CD4+ T cells. Individuals on methotrexate showed similar but less severe defects in vaccine response, whereas individuals on the B cell-depleting therapy rituximab had a near-total loss of antibody production after vaccination. These data define a specific cellular phenotype associated with impaired response to SARS-CoV-2 vaccination in patients with RA on different immune-modifying therapies and help inform efforts to improve vaccination strategies in this vulnerable population.

Published
2023
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