PHILADELPHIA, PA — In a groundbreaking study by The Wistar Institute, researchers led by Associate Professor Mohamed Abdel-Mohsen, Ph.D., have unearthed a potential link between sugar molecules in the blood and accelerated aging in people living with HIV (PLWH). Published in Nature Communications, their paper, “Immunoglobulin G N-glycan Markers of Accelerated Biological Aging During Chronic HIV Infection,” offers new insights into how chronic viral infections may advance biological aging processes, potentially explaining the higher incidence of age-related diseases among PLWH.
Despite the advancements in antiretroviral therapy (ART) that effectively suppress HIV to undetectable levels, the virus’s dormant persistence poses long-term health challenges. PLWH are more susceptible to conditions typically associated with aging, such as cancer and neurocognitive disorders, often at a younger age compared to the broader population. Abdel-Mohsen’s research delves into the molecular underpinnings of this phenomenon, focusing on the human glycome—the entirety of sugar structures in the body—and its role in immune system regulation.
The study’s novel approach centered on immunoglobulins (IgGs), which play a crucial role in the body’s immune response. It is known that as individuals age, the glycan composition attached to these IgGs shifts, diminishing their anti-inflammatory capabilities and enhancing pro-inflammatory attributes. Abdel-Mohsen and his team hypothesized that HIV might exacerbate these changes, contributing to accelerated biological aging and the early onset of related diseases.
Analyzing glycan profiles from over 1,200 participants, the team discovered distinct differences between PLWH and those without the virus. Those living with HIV showed elevated levels of inflammatory and pro-aging IgG glycan signatures. Leveraging machine learning, the researchers developed a model to use these glycan signatures to estimate the biological age of PLWH, offering a tool to potentially predict the early onset of comorbid conditions.
To ascertain whether these glycan changes were merely associated with or directly contributing to the observed clinical outcomes, the team engineered HIV-specific antibodies with altered IgG glycan modifications seen in PLWH. These modified antibodies demonstrated a reduced capacity for immune response in vitro, reinforcing the theory that sugar abnormalities directly impact health outcomes. Conversely, antibodies engineered to mimic the glycan profiles of biologically younger individuals showed enhanced virus-fighting capabilities, suggesting a possible avenue for therapeutic intervention.
“Utilizing glycan signatures to predict early onset of diseases in people living with HIV marks a pivotal shift towards proactive healthcare,” said Abdel-Mohsen. “This could significantly alter clinical outcomes, allowing for timely interventions and personalized treatment plans. The impact on treatment and management in the HIV community could be revolutionary. Beyond biomarkers, antibodies glycoengineered to mimic biologically younger glycans offer a new therapeutic avenue. This method could enhance immune responses, paving the way for innovative treatments.”
This research not only underscores the complexity of the immune system’s interaction with chronic viral infections but also opens the door to novel treatment strategies aimed at mitigating the adverse effects of accelerated aging in PLWH. By targeting the glycan composition of IgGs, it may be possible to develop therapies that rejuvenate the immune system, offering hope for improved quality of life and extended healthspan among those living with HIV.
For the medical community and PLWH, the implications of these findings are profound. They suggest a shift in focus towards the glycome as a critical factor in managing long-term health outcomes in HIV, emphasizing the need for comprehensive care strategies that address the multifaceted challenges of living with the virus. As researchers continue to explore the therapeutic potential of manipulating glycan profiles, this study marks a significant step forward in understanding and potentially altering the trajectory of aging in PLWH.
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