Cell Reports (Dec 2020)
HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound
- Rasmus Offersen,
- Wen-Han Yu,
- Eileen P. Scully,
- Boris Julg,
- Zelda Euler,
- Saheli Sadanand,
- Dario Garcia-Dominguez,
- Lu Zheng,
- Thomas A. Rasmussen,
- Madeleine F. Jennewein,
- Caitlyn Linde,
- Jessica Sassic,
- Giuseppe Lofano,
- Selena Vigano,
- Kathryn E. Stephenson,
- Stephanie Fischinger,
- Todd J. Suscovich,
- Mathias Lichterfeld,
- Douglas Lauffenburger,
- Erik S. Rosenberg,
- Todd Allen,
- Marcus Altfeld,
- Richelle C. Charles,
- Lars Østergaard,
- Martin Tolstrup,
- Dan H. Barouch,
- Ole S. Søgaard,
- Galit Alter
Affiliations
- Rasmus Offersen
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Infectious Diseases, Aarhus University Hospital, Aarhus 8000, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus 8000, Denmark
- Wen-Han Yu
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- Eileen P. Scully
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
- Boris Julg
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Zelda Euler
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Saheli Sadanand
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Dario Garcia-Dominguez
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Lu Zheng
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- Thomas A. Rasmussen
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus 8000, Denmark
- Madeleine F. Jennewein
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Caitlyn Linde
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Jessica Sassic
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Giuseppe Lofano
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Selena Vigano
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Kathryn E. Stephenson
- Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
- Stephanie Fischinger
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Todd J. Suscovich
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Mathias Lichterfeld
- Division of Infectious Disease, Brigham and Women’s Hospital, Boston, MA 02115, USA
- Douglas Lauffenburger
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
- Erik S. Rosenberg
- Division of Infectious Disease, Massachusetts General Hospital, Boston, MA 02114, USA
- Todd Allen
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- Marcus Altfeld
- Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany
- Richelle C. Charles
- Division of Infectious Disease, Massachusetts General Hospital, Boston, MA 02114, USA
- Lars Østergaard
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus 8000, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus 8000, Denmark
- Martin Tolstrup
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus 8000, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus 8000, Denmark
- Dan H. Barouch
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
- Ole S. Søgaard
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus 8000, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus 8000, Denmark
- Galit Alter
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Corresponding author
- Journal volume & issue
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Vol. 33,
no. 11
p. 108502
Abstract
Summary: Changes in antibody glycosylation are linked to inflammation across several diseases. Alterations in bulk antibody galactosylation can predict rheumatic flares, act as a sensor for immune activation, predict gastric cancer relapse, track with biological age, shift with vaccination, change with HIV reservoir size on therapy, and decrease in HIV and HCV infections. However, whether changes in antibody Fc biology also track with reservoir rebound time remains unclear. The identification of a biomarker that could forecast viral rebound time could significantly accelerate the downselection and iterative improvement of promising HIV viral eradication strategies. Using a comprehensive antibody Fc-profiling approach, the level of HIV-specific antibody Fc N-galactosylation is significantly associated with time to rebound after treatment discontinuation across three independent cohorts. Thus virus-specific antibody glycosylation may represent a promising, simply measured marker to track reservoir reactivation.
