Tag: 29/3/22

Fewer Types of Antibodies Produced with Age

old man walking with canes
Source: Miika Luotio on Unsplash

Using short-lived killifish to study how the immune system weakens with ageing, scientists have found that fewer types of antibodies are produced as organisms age. Published in eLife, the findings could lead to ways to rejuvenate the immune systems of older people.

The immune system has to constantly respond to new attacks from pathogens and remember them in order to be protected during the next infection. For this purpose, B cells build a library of information that can produce a variety of antibodies to recognise the pathogens.

“We wanted to know about the antibody repertoire in old age,” explained lead researcher Dario Riccardo Valenzano. “It is difficult to study a human being’s immune system over his or her entire life, because humans live a very long time. Moreover, in humans you can only study the antibodies in peripheral blood, as it is problematic to get samples from other tissues. For this reason, we used the killifish. It is very short-lived and we can get probes from different tissues.”

The shortest-lived vertebrates that can be kept in the laboratory, killifishes quickly age over their three to four month lifespan and have become the focus of ageing research in recent years due to these characteristics.

The researchers were able to accurately characterise all the antibodies that killifish produce. They found that older killifish have different types of antibodies in their blood than younger fish. They also had a lower diversity of antibodies throughout their bodies.

The discovery could lead to ways to rejuvenate the immune system. “If we have fewer different antibodies as we age, this could lead to a reduced ability to respond to infections. We now want to further investigate why the B cells lose their ability to produce diverse antibodies and whether they can possibly be rejuvenated in the killifish and thus regain this ability,” Valenzano said.

Source: Max Planck Institute for Biology of Ageing

IVF Babies Have Better Quality of Life as Adults

Pregnant with ultrasound image
Source: Pixabay

Being conceived via assisted reproductive technology (ART), such as IVF, could boost quality of life in adulthood, according to the results of a new study published in Human Fertility. The findings offer reassuring news for people who have been conceived with ART, and those who need to use the technology to conceive.

“Our findings suggest that being ART-conceived can provide some advantages on quality of life in adulthood, independent of other psychosocial factors,” said lead author Karin Hammarberg of Monash University. “Together with previous evidence that adults conceived by ART have similar physical health to those who were naturally conceived, this is reassuring for people who were conceived with ART—and those who need ART to conceive.”

In the more than four decades since the first birth following in vitro fertilization (IVF) in 1978, more than 8 million children have been born as a result of ART. In that time, many studies have evaluated the physical health, development and psychosocial well-being of ART-conceived children compared with those naturally conceived (NC). But currently, there is less known about the health and quality of life of adults who were conceived by ART.

The study recruited 193 young adults conceived through ART and 86 through NC. These participants completed questionnaires, which included a standardised quality of life measure (World Health Organization Quality of Life – Brief Assessment [WHOQoL-BREF]), when aged 18–28 years (T1) and again when aged 22–35 years (T2). The WHOQoL-BREF assesses four domains of quality of life: 1) physical 2) psychosocial 3) social relationships and 4) environment.

The researchers looked at the associations between factors present at T1 (mode of conception, the mother’s age when the participant was born, sexual orientation, family financial situation in secondary school, perceptions of own weight, number of close friends, frequency of vigorous exercise and quality of relationships with parents) and the scores on the four domains of WHOQoL-BREF at T2.

After making statistical adjustments to account for other psychosocial factors present in young adulthood, the results showed that being ART-conceived was strongly linked with higher scores (better quality of life) on both the social relationships and environment WHOQoL-BREF domains at T2. In addition, having less psychological distress, a more positive relationship with parents, a better financial situation, and perceptions of being about the right weight at T1 were associated with higher scores on one or more WHOQoL-BREF domains at T2.

“Children conceived via ART are nowadays a substantial part of the population—and it’s important to continue to evaluate the long-term effects of ART on their physical health and well-being as they progress through adolescence into adulthood,” said Hammarberg. “When accounting for other factors present in young adulthood, being ART-conceived appears to confer some advantages in quality of life. Perhaps unsurprisingly, we also found that, independently of how the person was conceived, having a better relationship with parents, less psychological distress, and a better family financial situation in young adulthood contributed to a better adult quality of life.”

This is the first study to explore the contributions of being conceived with ART and psychosocial factors present in young adulthood to the quality of life of adults. While the findings are reassuring, they should be interpreted with caution because many of those who took part in the first study did not take part in the follow-up study.

Source: Taylor & Francis

New Hope for Alopecia Treatment with JAK Inhibitor Baricitinib

Before and after images for participants who received 36 weeks of treatment for alopecia areata with baricitinib. Credit: Yale University

Results from a new study in three patients with alopecia areata treated with a Janus kinase (JAK) inhibitor, baricitinib, were able to regrow hair. The study is based on Phase III clinical trials using baricitinib – a drug commonly used for arthritis – to treat alopecia areata, a skin disease characterised by loss of hair from the scalp and sometimes eyebrows and eyelashes.

“This is so exciting, because the data clearly show how effective baricitinib is,” said Dr. Brett King, an associate professor of dermatology at the Yale School of Medicine and lead author of the new study, published in the New England Journal of Medicine. “These large, controlled trials tell us that we can alleviate some of the suffering from this awful disease.”

Alopecia areata is an autoimmune disorder in which the body’s immune system attacks hair follicles, and which typically occurs in people under the age of 40. At present there is no FDA-approved treatment for the disease.

To test the drug, the researchers conducted two large, randomised trials involving a total of 1 200 people. The participants were adults with severe alopecia areata, who had lost at least half of their scalp hair.

For 36 weeks, participants were randomised to either a daily dose of either 4mg of baricitinib, 2mg of baricitinib, or a placebo. One-third of the patients who received the larger dose grew hair back.

According to the researchers, baricitinib works by disrupting the communication of immune cells involved in harming hair follicles. Baricitinib and other JAK inhibitors are routinely used to treat autoimmune forms of joint disease.

“Alopecia areata is a crazy journey, marked by chaos, confusion, and profound sadness for many who suffer from it,” King said. “It will be incredible to have a medicine to help people emerge on the other side, normalcy restored, recognizable again to themselves and those around them.”

Over the past decade, A/Prof King has developed methods for using JAK inhibitors to treat a variety of skin diseases — including eczema, vitiligo, granuloma annulare, sarcoidosis, and erosive lichen planus.

A/Prof King noted that the clinical trials involving baricitinib are ongoing, allowing researchers to assess the long-term effectiveness and safety of the treatment.

Source: Yale University

Scientists Discover the Body’s Alarm System for Severe Blood Loss

Red blood cells
Source: Pixabay

In a discovery that could greatly benefit the treatment of traumatic injuries, scientists have identified a cluster of cells in the brainstem that control the body’s response to severe blood loss

The collection of neurons that the researchers discovered drive a response that maintains blood pressure during blood loss. However, severe blood loss eventually results in cardiovascular collapse, a condition called ‘decompensated haemorrhage’, marked by an abrupt and dangerous loss of blood pressure that presages haemorrhagic shock, where the body’s organs begin to shut down.

“During blood loss, the brain coordinates a cardiovascular response that supports blood flow to critical organs, like the heart and brain,” said researcher George Souza, PhD. “Our study shows that the cardiovascular response to blood loss depends on changes in the activity of a few hundred neurons in the brainstem.”

The new results, published in Cell Reports, shed light on an important process the body uses to maintain its blood pressure. Neurons, termed adrenergic C1 neurons, monitor blood pressure and activate during blood loss, increasing vasodilatory nerve activity that maintains proper blood pressure.

The scientists utilised advanced imaging and a technique called optogenetics controls neurons using light. Their research revealed that the C1 neurons are hyperactive during blood loss, and this keeps blood pressure study. But these neurons become inactive with severe blood loss, resulting in cardiovascular collapse.

The scientists found that re-activating the C1 neurons in lab rats restored both blood pressure and heart rate before cardiovascular collapse could lead to haemorrhagic shock.

“Our study indicates that reactivating the brain pathways controlling blood pressure during decompensated haemorrhage effectively reverses cardiovascular collapse. We think this indicates that neuromodulation of the pathways described by our study could be a beneficial adjunct therapy for low blood pressure following blood loss,” explained lead researcher Stephen Abbott, PhD.

The researchers noted that more research is needed as several factors could also cause the C1 neurons’ drop in activity during the onset of decompensated haemorrhage.

“These findings illuminate the importance of the brain-body interactions during blood loss and provide a new perspective for the underlying cause of cardiovascular collapse,” Dr Abbott said.

Source: University of Virginia Health System

Why HIV Still Lingers in Patients’ Bodies

HIV invading a human cell
HIV invading a human cell: Credit NIH

Even with antiretroviral therapy, HIV still lingers in the body, preventing complete cure. Now, new research published in PLOS Pathogens, revealed a possible answer to why HIV persists in the body: a lack of a certain protein in HIV patients’ killer T cells. The discovery also explained why people with HIV have less risk of developing multiple sclerosis (MS).

Because this protein, CD73 is responsible for migration and cell movement into the tissue, the lack of the protein compromises the ability of killer T cells to find and eliminate HIV-infected cells, explained immunologist Shokrollah Elahi, lead researcher of the study.

“This mechanism explains one potential reason for why HIV stays in human tissues forever,” he said, adding that the research also shows the complexity of HIV infection.

“This provides us the opportunity to come up with potential new treatments that would help killer T cells migrate better to gain access to the infected cells in different tissues.”

After spending three years identifying the role of CD73, Elahi turned his focus to understanding potential causes for the drastic reduction. He found it is partly due to the chronic inflammation that is common among people living with HIV.

“Following extensive studies, we discovered that chronic inflammation results in increased levels of a type of RNA found in cells and in blood, called microRNAs,” he explained. “These are very small types of RNA that can bind to messenger RNAs to block them from making CD73 protein. We found this was causing the CD73 gene to be suppressed.”

This discovery also helps explain why people with HIV have a lower risk of developing MS, Elahi noted.

“Our findings suggest that reduced or eliminated CD73 can be beneficial in HIV-infected individuals to protect them against MS. Therefore, targeting CD73 could be a novel potential therapeutic marker for MS patients.”

Elahi said the research could next look into seeing how to turn on the CD73 gene in patients with HIV and off in those with MS.

Source: University of Alberta