According to the Wistar Institute’s associate professor Mohamed Abdel-Mohsen, Ph.D., and his team, they have discovered sugar abnormalities in the blood that could lead to biological aging and inflammation in people living with HIV (PLWH). The findings, based on a study with over 1200 participants, are outlined in the new paper, “Immunoglobulin G N-glycan Markers of Accelerated Biological Aging During Chronic HIV Infection,” discusses the persistent nature of HIV despite advances in treatment. It emphasizes the long-term health issues associated with the virus, such as inflammation and the increased risk of aging-related diseases. The author, Abdel-Mohsen, aims to explore the mechanisms behind the chronic viral infection.Infection is responsible for this faster biological aging process, where the body ages at a quicker rate than it normally should based on a person’s age. By studying the molecular mechanisms of accelerated biological aging in individuals with chronic viral infections, scientists can develop methods to reduce the harmful effects.
Although there are numerous factors that can lead to accelerated biological aging, researchers have honed in on a new factor: irregularities in the human glycome – the collection of all the different sugar structures present in the body. Previous research has already linked aging to abnormalities in the glycome.The article discusses changes in the glycan composition of immunoglobulins (IgGs) as people age. IgGs are important for immune regulation, but as individuals get older, their IgGs lose their anti-inflammatory properties and become more pro-inflammatory.
Abdel-Mohsen’s research focuses on whether living with a chronic viral infection, like HIV, can worsen these changes and lead to premature aging and related diseases.
By analyzing glycan profiles in over 1200 individuals, including those with and without HIV, the research team found that people living with HIV have higher levels of inflammatory and pro-aging IgG glycan signatures. This discovery is a significant advancement in understanding the effects of chronic viral infections on aging.A machine-learning model has been developed to use glycan signatures for estimating the biological age of PLWH and determining the rate of aging acceleration. It is also believed that this glycan signature could potentially predict the onset of comorbid conditions in PLWH, such as cancer, years in advance.
In order to confirm that these disruptions associated with glycans were not just correlative, but rather causal, the research team created HIV-specific antibodies that were engineered to display the same abnormal IgG glycan modifications seen in PLWH. Testing these engineered antibodies in vitro confirmed that the modified antibodies were less effective at mounting an immune response.Research shows that modified antibodies with sugar abnormalities may play a direct role in the poor clinical outcomes observed. By designing antibodies with glycans similar to those found in younger individuals, they showed an increased ability to enhance the immune system’s ability to fight virus-infected cells. “Using 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 have a significant impact on clinical outcomes and allow for timely intervention.The use of ions and personalized treatment plans could have a revolutionary impact on treatment and management within the HIV community. In addition to biomarkers, antibodies that have been glycoengineered to mimic biologically younger glycans present a new avenue for therapy. This approach has the potential to enhance immune responses and pave the way for innovative treatments.
