Medical Bulletin 26/ February/ 2024

A research published in the journal Science Immunology on 23 February 2024 reveals that newborns’ T cells – white blood cells that protect from disease – outperform those of adults at fightingnumerous infections.

Adult T cells surpass newborn T cells in tasks such as antigen recognition, immunological memory formation, and response to recurring infections. This had led to the assumption that infant T cells were weaker than adult T cells. However, the COVID-19 pandemic revealed a surprising lack of illness in infants, challenging the assumption.

The research co-led by Brian Rudd, associate professor of microbiology and immunology, and Andrew Grimson, professor of molecular biology and genetics from Cornell University, showed that newborn T cells are not deficient: Instead, they are involved in a part of the immune system that does not require antigen recognition: the innate arm of the immune system.

While adult T cells use adaptive immunity – recognising specific germs to fight them later ­– newborn T cells are activated by proteins associated with innate immunity, the part of the immune system that offers rapid but nonspecific protection against microbes the body has never encountered.

“Our paper demonstrates that neonatal T cells are not impaired, they are just different than adult T cells and these differences likely reflect the type of functions that are most useful to the host at distinct stages of life,” Rudd said.

Neonatal T cells can participate in the innate arm of the immune system. This enables newborn T cells to respond during the very first stages of an infection and defend against a wide variety of unknown bacteria, parasites and viruses, which the adult T-cells cannot do.

“We know that neonatal T cells don’t protect as well as adult T cells against repeat infections with the same pathogen. But neonatal T cells have an enhanced ability to protect the host against early stages of an initial infection,” Rudd said. “So, it is not possible to say adult T cells are better than neonatal T cells or neonatal T cells are better than adult T cells. They just have different functions.”

References: SCIENCE IMMUNOLOGY, Vol 9, Issue 92, DOI: 10.1126/sciimmunol.adf8776

Researchers uncover promising findings about the role of vitamin B6 in pancreatic cancer

A recent study published in the journal Cancer Discovery highlights the dual role of vitamin B6 in both maintaining health in individuals without pancreatic cancer and its implications when the disease is present.

Vitamin B6, found in chicken, fish, and bananas, supports immune cells like natural killer (NK) cells crucial for combatting cancer and infections. However, in pancreatic cancer, NK cells decline as cancer cells consume B6 for their growth. This competition highlights the significance of B6 in immune function and its role in cancer progression.

“Pancreatic cancer is very difficult to treat, and only 11% of people who are diagnosed survive for five years,” said Kamiya Mehla, Ph.D., associate professor of oncology science in the OU College of Medicine and a researcher with the OU Health Stephenson Cancer Center.

“It’s important that researchers study pancreatic cancer from many different angles in order to develop new treatments. My laboratory is focused on the role of vitamin B6 because we know it boosts the immune system, but we need to understand more about how it affects cancer cells. We hope that our work opens new avenues for developing novel treatments for pancreatic cancer.”

In the study, Mehla found that giving more vitamin B6 doesn’t help the NK cells – the pancreatic cancer cells grew more when they could consume additional nutrients. She studied the actions that cancer cells take to deplete vitamin B6, then devised ways to impede them. She discovered a three-part strategy. Step one involves reducing the expression of a particular gene in order to block the pathway through which the cancer takes up vitamin B6. The second step is to supply more vitamin B6, and the third utilizes a therapy to enhance the function of NK cells, like a tune-up for a car engine. When the strategy was tested in mice, it reduced the amount of pancreatic cancer cells.

“That was encouraging to discover and it is important to know because the immune system needs to be strong in order for other treatments, like chemotherapy, to be effective. Therapy will not work if the immune system is not able to do its part.”said Mehla.

Because pancreatic cancer causes problems throughout the body in its attempt to gain more nutrients, the study was crucial in determining how a shortfall of vitamin B6 affects other organs, particularly the liver, when cancer cells are present and whether a lack of vitamin B6 contributes to the onset of cachexia, a muscle-wasting condition that affects the majority of people with pancreatic cancer.

Reference: Cancer Discovery; https://doi.org/10.1158/2159-8290.CD-23-0334

New study links IgG immunoglobulin's glycan coating with cardiovascular health

A recent study from Brigham and Women's Hospital, a founding member of Mass General Brigham, has found that while cholesterol is a major contributor to heart disease, a glycan biomarker of IgG is also an important predictor for cardiovascular diseases (CVD).

The glycan sugar coating on IgG immunoglobulin plays a crucial role in modulating immune responses and maintaining overall health. This coating, consisting of complex sugar molecules attached to the protein structure of IgG, influences various aspects of immune function, including antibody stability, binding affinity, and interaction with immune cells. Alterations in the glycan composition of IgG have been linked to various diseases, including autoimmune disorders, infectious diseases, and cancer.

The researchers studied the sugar coatings on an antibody known as immunoglobulin G (IgG), which is implicated in the immune responses associated with chronic inflammation among participants in two case-control studies.Using conditional logistic regression, they investigated the association of future CVD with baseline IgG N-glycans and a glycan score adjusting for clinical risk factors such as statin treatment, age, sex, race, lipids, hypertension, and smoking. Using least absolute shrinkage and selection operator regression, an IgG glycan score was derived as a linear combination of selected IgG N-glycans.

The study found that specific IgG N-glycans were linked to cardiovascular disease (CVD) in both case-control studies. One agalactosylated glycan (IgG-GP4) showed a positive association, whereas three digalactosylated glycans (IgG glycan peaks 12, 13, 14) and two monosialylated glycans (IgG glycan peaks 18, 20) exhibited negative associations with CVD. These findings suggest that the sugar coatings on IgG directly influence CVD risk, likely through inflammatory mechanisms. Additionally, an IgG glycan score was identified as a predictor of future cardiovascular events, independent of other risk factors.

"IgG N-glycans which are the sugar coatings that modify the IgG immunoglobulins might not be only novel biomarkers for cardiometabolic health, but also potential new drug targets," said Samia Mora, MD, MHS, of Brigham's Divisions of Preventative and Cardiovascular Medicine. "Our results represent a promising and underappreciated novel biomarker that has great potential for risk stratification, CVD prevention, diagnostics and treatment purposes."

References: https://doi.org/10.1161/CIRCRESAHA.123.323623