Tag: 14/11/25

Categories : Expert Opinion IT in HealthcareTags :

Digital Tools Can Transform Africa’s Healthcare Outcomes – And Save the Continent Billions

On By ModernMedia
AI image created with Gencraft

By Thom Renwick, General Manager, Roche Pharma South Africa

Early screening and treatment. Much higher survival rates. And savings in the billions of dollars. From AI-powered medicine development to teleconsultations, technology can boost Africans’ health and livelihoods while growing economic and social impact across the continent.

Access to quality healthcare is fundamental to leading a fruitful, economically active life. Yet, breast cancer is still the number one cancer killer of women in Africa – in most cases, while they’re still in their prime. Tragically, most are diagnosed too late for curative treatment.

Across the continent, non-communicable diseases – such as treatable breast cancer – cause hundreds of thousands of preventable deaths every year[1], devastating families and hampering economic growth.

Global projections indicate a worrying 38% rise in incidence of breast cancer and a 68% increase in deaths by 2050 without urgent intervention, with the least developed countries being the most affected, according to a new white paper[2] by independent German economic think tank the WifOR Institute.

The Value of Investing in Innovative Medicines report outlines the economic burden from not treating the aggressive HER2-positive type of breast cancer over five years in seven African countries – South Africa, Kenya, Nigeria, Algeria, Tunisia, Côte d’Ivoire and Morocco. The findings are staggering, indicating a $10.3-billion loss in productivity from 2017 to 2023.[3]

The data also shows that, in Africa, 89% of the economic burden of HER2-positive breast cancer – representing 15% to 20% of all breast cancer cases around the world – falls on women of working age.[4]

It goes beyond economics. Mothers hold households together and when they die that has huge ramifications for entire families and communities.

In sub-Saharan Africa, every 100 deaths among women under 50 leave around 210 children without their mothers[5], resulting in unstable, vulnerable households and long-term developmental challenges.

These figures are a wake-up call, but in challenge lies scope for innovation. I believe we can – and must – turn the burden into opportunity.

Closing the gap through health-tech partnerships

Every woman diagnosed and treated early is not only more likely to survive but also able to remain active in her family and community[6], contributing to shared prosperity.

Through healthcare and technology partnerships, we can leapfrog traditional healthcare models and turn the tide towards survival.

Excitingly, this process has already started. Governments are increasingly setting strategies and allocating funding for digital health. Start-ups and companies are driving the uptake of digital health tools that could revolutionise care delivery.

Artificial intelligence stands out as the breakthrough technology. Pharmaceutical and biotech companies such as Roche are already using AI throughout their value chains, both in the early stage of drug development and also to correctly interpret the enormous amounts of data generated to deliver effective health solutions.

In most sub-Saharan countries, more than 20% of the population lives more than two hours from essential health services.[7] Tech’s role in Africa’s future is about much more than connectivity or commerce. It’s about lives and well-being – AI, apps, telemedicine and other digital solutions can close the gap to bring care closer to people.

But without individuals and organisations working together, innovation can’t come to life.

And since the journey for a patient experiencing a health crisis such as breast cancer involves many stakeholders, we must urgently identify opportunities for partners to come together and spur real action.

This week, Roche sponsored the 28th annual Africa Tech Festival’s first-ever health track. Policymakers, innovators, professionals and experts met to thrash out actionable solutions to the continent’s biggest health challenges.

This was part of an ambitious broader strategy to transform healthcare in Africa – investment in early intervention strategies can generate returns that far outstrip their cost.

Research by McKinsey & Company shows that the African digital health space is already seeing unprecedented growth, with $123-million in investment secured by 55 start-ups in 2021.[8]

The consultancy’s analysis showed that digital health tools – such as virtual platforms for consultations; electronic health records; mobile apps to help patients self-manage their diseases; and patient e-booking platforms – could help South Africa, Kenya and Nigeria capture efficiencies of up to 15% in total healthcare expenditure by 2030.[9]

Widespread adoption could free up an astounding $1.9-billion to $11-billion in South Africa alone.[10]

Speaking with one voice for a better future

Innovation has been the backbone of progress across any major public health disease – whether it’s HIV, cancer or ophthalmology. It takes a combination of passionate people and expert innovation to make a difference.

One existing solution and real-life example of African innovation and partnership is EMPOWER, a groundbreaking digital health platform developed to improve coordinated breast and cervical cancer care in Kenya.[11]

The initiative has grown from a single clinic in 2019 to a 76-site national platform and is integrated into Kenya’s National Cancer Registry.[12]

Empower ensures that the entire patient journey, from screening to treatment and follow-up, is digitally powered.

The current average five-year survival rate for breast cancer across Africa is roughly five out of 10 patients that are diagnosed (48%).[13] My vision is that this will increase to 80% within the next 5 years.

Realising this audacious goal will take commitment from stakeholders to drive action for the tens of thousands of African women who desperately need it.

There is no reason why someone in a Western society should have a better health outcome than here in Africa. The health of our people is the wealth of our nations. We must speak with one voice and act now.

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Thom Renwick is general manager of Roche South Africa and the sub-region. He began his journey with the company in 2012 on its United Kingdom graduate programme, following his studies at King’s College London, Cranfield School of Management and the University of Oxford.

During his career at Roche, he has worked in global product strategy in Basel, Switzerland, as head of ophthalmology in the UK and as chief of staff for Pharma International. He won the PharmaTimes New Marketer of the Year Award in 2015 and was featured in the publication’s Smart People series in 2021.

[1] World Health Organisation African region. https://www.afro.who.int/health-topics/noncommunicable-diseases. Accessed: Nov. 12, 2025. [Online]. Available: https://www.afro.who.int/health-topics/noncommunicable-diseases.

[2] WifOR Institute, ‘The Value of Investing in Innovative Medicines: Socioeconomic Burden of HER2+ Breast Cancer and Annual Social Impact of Roche’s Treatments for the Disease in Africa’. Accessed: Nov. 7, 2025 [Online]. Available: https://africa.roche.com/stories/what-s-it-worth-the-value-of-innovation

[3] WifOR Institute, ‘The Value of Investing in Innovative Medicines: Socioeconomic Burden of HER2+ Breast Cancer and Annual Social Impact of Roche’s Treatments for the Disease in Africa’. Accessed: Nov. 7, 2025 [Online]. Available: https://africa.roche.com/stories/what-s-it-worth-the-value-of-innovation

[4] WifOR Institute, ‘The Value of Investing in Innovative Medicines: Socioeconomic Burden of HER2+ Breast Cancer and Annual Social Impact of Roche’s Treatments for the Disease in Africa’. Accessed: Nov. 7, 2025 [Online]. Available: https://africa.roche.com/stories/what-s-it-worth-the-value-of-innovation

[5] WifOR Institute, ‘The Value of Investing in Innovative Medicines: Socioeconomic Burden of HER2+ Breast Cancer and Annual Social Impact of Roche’s Treatments for the Disease in Africa’. Accessed: Nov. 7, 2025 [Online]. Available: https://africa.roche.com/stories/what-s-it-worth-the-value-of-innovation

[6] WifOR Institute, ‘The Value of Investing in Innovative Medicines: Socioeconomic Burden of HER2+ Breast Cancer and Annual Social Impact of Roche’s Treatments for the Disease in Africa’. Accessed: Nov. 7, 2025 [Online]. Available: https://africa.roche.com/stories/what-s-it-worth-the-value-of-innovation

[7] Mckinsey, ‘How digital tools could boost efficiency in African health systems.’ Accessed: Nov. 7, 2025 [Online]. Available: https://www.mckinsey.com/industries/healthcare/our-insights/how-digital-tools-could-boost-efficiency-in-african-health-systems

[8] Mckinsey, ‘How digital tools could boost efficiency in African health systems.’ Accessed: Nov. 7, 2025 [Online]. Available: https://www.mckinsey.com/industries/healthcare/our-insights/how-digital-tools-could-boost-efficiency-in-african-health-systems

[9] Mckinsey, ‘How digital tools could boost efficiency in African health systems’. Accessed: Nov. 7, 2025 [Online]. Available: https://www.mckinsey.com/industries/healthcare/our-insights/how-digital-tools-could-boost-efficiency-in-african-health-systems

[10] Mckinsey, ‘How digital tools could boost efficiency in African health systems’. Accessed: Nov. 7, 2025 [Online]. Available: https://www.mckinsey.com/industries/healthcare/our-insights/how-digital-tools-could-boost-efficiency-in-african-health-systems

[11] Roche Africa, ‘From vision to national platform: EMPOWER scales through Kenya’s National Cancer Institute’. Accessed: Nov. 7, 2025 [Online]. Available: https://africa.roche.com/stories/empower-scales-through-kenya-national-cancer-institute

[12] Roche Africa, ‘From vision to national platform: EMPOWER scales through Kenya’s National Cancer Institute’. Accessed: Nov. 7, 2025 [Online]. Available: https://africa.roche.com/stories/empower-scales-through-kenya-national-cancer-institute

[13] A. Padu-Pebrah, et al., ‘Five-Year Survival Outcomes for Breast Cancer Patients Across Continental Africa: A Contemporary Review of Literature with Meta Analysis’, eLife. Accessed: Nov. 7, 2025 [Online]. Available: https://elifesciences.org/reviewed-preprints/105488#mainMenu

Categories : Neurology Surgeries & ProceduresTags :

Surgeons Perform ‘Miraculous’ Reattachment of 2-year-old’s Severed Spinal Cord

On By ModernMedia
Oliver Staub, 2, smiles while recovering from two complex spinal cord surgeries at UChicago Medicine Comer Children’s Hospital that reattached his head to his spinal cord. Image credit: University of Chicago Medicine

With monitors quietly beeping and multiple tubes going into his small body, Oliver Staub lay in a hospital bed as his parents tearfully started saying goodbye.

On April 17, an armoured car going 70mph (112kph) slammed into the family’s minivan during their vacation in Mexico. Everyone in the car was injured, but no one more than Oliver.

The impact disconnected the 2-year-old’s head from his spine, resulting in a transection of his spinal cord.

Doctors offered a grim prognosis. They told Oliver’s parents, Laura and Stefan, that their son’s neck was broken, he was a quadriplegic, brain dead and would die in a matter of days.

But following a surreal turn of events – which included support from German soccer star Toni Kroos, viral Instagram posts, and traveling more than 2,000 miles for two risky spinal cord surgeries at the University of Chicago Medicine Comer Children’s Hospital — Oliver is now talking, laughing, smiling, moving his fingers and toes and starting to breathe on his own.

“To see someone survive an injury like this? Nothing like this has ever been reported in neurosurgery or spinal cord injuries,” said Mohamad Bydon, MD, Chair of the Department of Neurological Surgery at UChicago Medicine and health system leader for Neurological Surgery, who performed Oliver’s surgeries in July with a multidisciplinary team of surgeons.

“We didn’t think he’d ever be able to move, and now he’s moving all four limbs,” Bydon said. “This is a unique and special case. It’s beyond our wildest expectations.”

‘We have a reason to fight’

As family members gathered at the Mexico City hospital to say goodbye, something incredible happened: Oliver began to show signs of recovery.

His eyes would follow his parents when they were in the room. Stefan and Laura raised the issue with his doctors, who ultimately determined that their son did, in fact, have brain function. They kept his life-sustaining ventilator on.

“It was at that moment that I thought, ‘We have a reason to fight,’” Laura said. “My son was there.”

When doctors could do nothing more for Oliver, they trained his parents on how to care for him and operate his ventilator. Wearing a neck collar and vest to stabilise his head – which, internally, was not connected to his body – Oliver was moved to his grandparents’ home eight hours away, near Morelia, Mexico.

With help from a daily nurse visit, Oliver survived for two months without moving and once having an incident of cardiac arrest. Bydon finds this astounding, given how unlikely it is that someone with an unstable, transected spine could survive at all, much less under the care of his parents.

“If Oliver’s parents and caretakers had made one wrong move in those two months, it could have resulted in death,” Bydon said.

A journey to Chicago

Stefan and Laura researched treatments for severe spinal cord injuries, hoping to provide a better life for their son. They contacted top spinal cord specialists around the world, including Bydon, whose groundbreaking stem cell therapy research impressed them.

They were repeatedly told that surgery, and the travel involved, would be too risky. But Bydon saw hope, in part because Oliver had survived this long.

“You should never count out a 2-year-old. They can surprise you,” Bydon said. “But it would require a complex multidisciplinary team, which is where the University of Chicago could help.”

The surgery needed to be done as soon and safely as possible, Bydon told them.

But travel to the United States for the surgery would be difficult and expensive. The Staubs received aid from family, friends and charities, but were still far short of what they needed.

Global outreach and support

A friend encouraged them to write to the Toni Kroos Foundation, the soccer player’s charity which helps seriously ill children. Stefan and Laura knew it was a long shot.

Two days later, the phone rang at midnight. It was foundation director Claudia Bartz. She’d seen Oliver’s journey on Instagram and was so moved by his story, she decided the foundation would cover the cost of Oliver’s surgery and transport to Chicago.

“We cried and cried. We couldn’t believe it,” Laura said, adding that they only posted on Instagram to keep their friends and family updated on Oliver. “None of this would have been possible without Toni Kroos.”

Oliver soon became a top-trending news story in Germany and their Instagram account blew up, going from a few hundred followers to more than 100 000. Strangers across the world continue to hold fundraisers and prayer vigils, sending the family encouraging messages and donations for his medical expenses.

“We would gladly trade all of this to go back to our normal life,” said Laura, who still has large scars on her head from the accident. “What I’m seeing here? It’s miraculous. We call it ‘The Oliver Effect.’ This is bigger than us.”

‘Harrowing’ surgery, major recovery

When Oliver arrived at Comer in July via medical jet, Bydon performed the first surgery, an occipital cervical fusion, with a team of UChicago Medicine surgeons.

This surgery for a 2-year-old is risky, not only because of how long it is, but also because a toddler cannot tolerate blood loss.

The surgery involved reconstructing Oliver’s spine, repairing his spinal cord and stabilising the back of his head to his cervical spine using titanium rods and screws.

The second surgery, two days later, stabilised the front of his spinal cord and repaired a spinal cord herniation.

“Those first few days after the surgeries were harrowing,” Bydon said. “His heart stopped at one point, and he had swelling in the brain.”

But about five days later, Oliver was making progress and smiled for the first time since the accident. One month later, he was able to grab his mom’s hand, push someone away and recognise the sensation that he needs to urinate. Most impressively, Bydon said, he can now take breaths on his own.

“We know the spine is communicating with the brain and body again,” Bydon said.

Moving forward with family

Oliver was discharged from Comer Children’s on August 15. The family will permanently move from Germany to Mexico, near Laura’s family, and now have hope for the future.

Oliver will have regular physical therapy and take medications for inflammation. In about six months, he’ll be able to remove his neck brace, Bydon said.

Laura and Stefan plan to return to Comer in spring 2026, when Bydon may be able to use novel stem cell therapy clinical trials to improve Oliver’s physical functions, pending special FDA approval.

Stefan and Laura said they’ll always be grateful to Bydon and UChicago Medicine.

“He didn’t promise us a miracle,” Laura said, “but he delivered one.”

Source: University of Chicago Medicine

Categories : CancerTags :

Pancreatic Cancer Forms ‘Synapses’

On By ModernMedia
Immunofluorescence image of pancreatic cancer cells that invade nerves: nerve cells appear in green, tumor cells in red.

Pancreatic cancer is one of the deadliest types of tumours. A team at the Technical University of Munich (TUM) has discovered that pancreatic tumours exploit the body’s nervous system by forming so-called pseudosynapses. Through a specific receptor, the cancer cells take up the neurotransmitter glutamate, which drives tumour growth. The researchers now hope to identify drugs that can block this process in patients.

It has been known for some time that the nervous system can affect cancer development. For example, nerve cells from healthy tissue can grow into tumors, a phenomenon known as “neural invasion,” which is typically linked to a poor prognosis.

About six years ago, a US research group discovered a new mechanism in the brain: tumours can form their own synapses, co-opting neuronal communication for their benefit. Professor Ekin Demir, a clinician scientist at the Department of Surgery at the TUM University Hospital, and his team built on this finding to investigate whether tumours outside the brain might form similar structures.

Searching for “tumour synapses”

Pancreatic tumours often show neural invasion. Thus, if such synapse-like structures existed outside the brain, this was the most likely place to find them. The researchers searched pancreatic tumour tissue for clusters of receptors specialised for specific neurotransmitters. In some samples, they did indeed find a strong concentration of NMDA receptors – the receptors that bind glutamate. Then came the successful search for the characteristic structures of synapses, carried out in the classic way under the electron microscope Owing to subtle physiological differences compared with typical neuronal synapses, the researchers refer to these structures as pseudosynapses.

Calcium waves promote tumour growth

What advantage do pancreatic tumours gain by forming pseudosynapses? Like other glands, the pancreas is regulated by the nervous system. Depending on the body’s needs healthy pancreatic cells receive the neurotransmitter glutamate through their synapses. This triggers a series of processes. Pseudosynapses exploit this natural mechanism. “When glutamate binds to the cancer cells’ NMDA receptors, a channel opens and calcium flows into the cell,” explains Professor Demir. “This influx triggers molecular signalling cascades that drive tumour growth and metastasis.” The team observed that the cancer cells generate characteristic slow, long-lasting calcium waves that drive tumour growth in a sustained way.

Yet this remarkable mechanism may open up a path to new cancer therapies. In mouse experiments, the researchers successfully blocked the NMDA receptors on tumour cells with a drug. The result: pancreatic tumours grew more slowly, developed fewer metastases, and the animals lived longer.

“We are currently using bioinformatic methods to identify approved drugs that, in addition to their primary effects, can also block these specific NMDA receptors in pancreatic cancer cells,” says Professor Ekin Demir. “Therapies targeting the interface between the nervous system and tumours could open up entirely new treatment options.” The team suspects that other tumour types may also form pseudosynapses to accelerate their growth.

The study is published in Cancer Cell.

Source: Technical University of Munich

Categories : Respiratory DiseasesTags :

Lung Study Reveals Why Deep Sighs Are Actually Good for Us  

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Photo by Julian Jagtenberg on Pexels

The surface of the lungs is covered with a fluid that increases their deformability. This fluid has the greatest effect when you take deep breaths from time to time, as researchers at ETH Zurich have discovered using sophisticated measurement techniques in the laboratory.  In their study, published in Science Advances, they found that it reorders the thin films created by lung fluids.

More than half of all premature babies born before the 28th week of pregnancy develop respiratory distress syndrome shortly after birth. As their lungs are not yet fully developed, they produce too little of the seemingly magical fluid that reduces surface tension in the lungs. As a result, some alveoli collapse – and the lungs are unable to get enough oxygen.  

Lungs become more deformable

Until 40 years ago, this usually spelled death. But then, in the late 1980s, pediatricians developed a life-saving procedure: they extracted the fluid from animal lungs and injected it into the lungs of premature babies. “This works very well in newborns,” says Jan Vermant, Professor of Soft Materials at ETH Zurich. “The fluid coats the entire surface, making the lungs more deformable or – with a more technical word – compliant.”  

But even in adults, lungs can fail. During the coronavirus pandemic, around 3000 people in Switzerland developed acute respiratory distress syndrome. Injecting surface-active fluid from animal lungs into the lungs of adults, however, does not help. “This shows that it’s not just about reducing surface tension,” as Vermant states. “We believe that mechanical stresses within the fluid also play an important role.”  

In collaboration with scientists from Spain, Belgium and the USA, his research group harnessed sophisticated measurement techniques to investigate precisely how lung fluid behaves when it is stretched and recompressed in the laboratory. The fluid in our bodies is also subjected to similar movements when the lungs expand during inhalation and contract again during exhalation.

Explanation for the feeling of relief in the chest  

In their experiments, the researchers simulated the movements of normal and particularly deep breaths – measuring the surface stress of the fluid in each case. “This surface stress influences how compliant the lungs are,” explains Vermant. The more compliant the lungs are, the less resistance there is to expansion and contraction – and the easier it is to breathe.  

With the help of their measuring instruments, the researchers found that surface stress decreases significantly after deep breaths. Apparently, there is a physical explanation for the feeling of relief experienced in the chest that often occurs after a deep sigh. The explanation starts from realising that the thin film formed by the lung fluid on the surface of the lungs actually consists of several layers.  

“Directly at the boundary with the air, there is a slightly stiffer surface layer. Underneath, there are several layers that should be softer than the surface layer,” explains Maria Novaes-Silva, a doctoral student in Vermant’s research group and first author of the study. As she has proven in experiments, this layering returns to the equilibrium configuration over time when the fluid does not move at all or moves only slightly during shallow breathing.  

Reconstructing multilayered structures  

A deep breath is needed from time to time to restore this ideal layering. Based on their analyses, the researchers have discovered that the pronounced stretching and compression of the pulmonary fluid causes the composition of the outer layer to change. ” There is an enrichment of saturated lipids, this results in a more densely packed interface,” says Novaes-Silva. Vermant adds: “This is a state outside of the boundaries of the thermodynamic equilibrium that can only be maintained through mechanical work.”  

It is also known from clinical practice that lung compliance gradually changes over time – and that breathing becomes increasingly difficult in connection with constant shallow breathing. The measurements in the laboratory therefore seems to reflect observations from the clinic. Novaes-Silva concludes: “These similarities are indications that we have captured real properties with our experimental setup.”  

Can the new insights gained by materials scientists also be used to derive expedient conclusions and insights for lung failure in adults? “A promising approach is to identify components that can artificially reconstruct multilayered structures,” the researchers note in their technical article. In conversation, Vermant points to therapies involving foam that are currently being developed and researched in greater depth by other groups. 

Source: ETH Zurich

Categories : Immune SystemTags :

Researchers Discover that Lupus is Triggered by Epstein-Barr Virus

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A woman with Systemic Lupus Erythematosus. Source: Wikimedia CC0

Epstein-Barr virus (EBV) one, of humanity’s most ubiquitous infectious pathogens, is to blame for systemic lupus erythematosus Stanford Medicine investigators and their colleagues have found.

The Epstein-Barr virus (EBV), which resides silently inside 95% of the world’s population, is directly responsible for making a minuscule number of immune cells go rogue and persuade far more of their fellow immune cells to launch a widespread assault on the body’s tissues, the scientists have shown.

The findings were published in Science Translational Medicine.

“This is the single most impactful finding to emerge from my lab in my entire career,” said William Robinson, MD, PhD, a professor of immunology and rheumatology and the study’s senior author. “We think it applies to 100% of lupus cases.”

The study’s lead author is Shady Younis, PhD, professor and instructor in immunology and rheumatology.

About five million worldwide – 90% of them women – have lupus in which the immune system attacks the contents of cell nuclei. This results in damage to organs and tissues throughout the body, with symptoms varying widely among individuals.

Practically the only way to not get EBV is to live in a bubble.”

With appropriate diagnosis and medication, most lupus patients can live reasonably normal lives, but for about 5% of them the disorder can be life-threatening, said Robinson,. Existing treatments slow down disease progression but don’t cure it, he said.

The virus meets the B cell

By the time we’ve reached adulthood, the vast majority of us have been infected by EBV. Transmitted in saliva, EBV infection typically occurs in childhood, from sharing a spoon with or drinking from the same glass as a sibling or a friend, or maybe during our teen years, from exchanging a kiss. EBV can cause mononucleosis, “the kissing disease,” which begins with a fever that subsides but lapses into a profound fatigue that can persist for months.

“Practically the only way to not get EBV is to live in a bubble,” Robinson said. “If you’ve lived a normal life,” the odds are nearly 20 to 1 you’ve got it.

Once you’ve been infected by EBV you can’t get rid of it, Robinson said, even if you remain or become symptom-free. EBV belongs to a large family of viruses, including those responsible for chickenpox and herpes, that can deposit their genetic material into the nuclei of infected cells. There the virus slumbers in a latent form, hiding from the immune system’s surveillance agents. This may last as long as the cell it’s hiding in stays alive. Or, under certain conditions, the virus may reactivate and force the infected cell’s replicative machinery to produce myriad copies of themselves that break out to infect other cells and other people.

Among the cell types in which EBV takes up permanent residence are B cells, immune cells that do a couple of important things after they ingest bits of microbial pathogens. For one, they can produce antibodies: customised proteins that find and bind immune-system-arousing proteins or other molecules (immunologists call them “antigens”) on microbial pathogens that have infected an individual, or are trying to. For another, B cells are “professional antigen-presenting cells”: They can process antigens and display them on their surfaces to encourage other immune cells to raise the intensity of their hunt for the pathogen in question. That’s a substantial force multiplier for kick-starting an immune response.

Our bodies harbour hundreds of billions of B cells, which, through many cell divisions, develop an enormous diversity of antibodies. In the aggregate, these antibodies can bind an estimated 10 billion to 100 billion different antigenic shapes. This is why we’re able to mount a successful immune response to so many different pathogens.

Oddly, about 20% of the B cells in our bodies are autoreactive. They target antigens belonging to our own tissues – not by design, but due to the random way B-cell diversity comes about: through sloppy replication, apparently engineered by evolution to ensure diversification. Fortunately, these B cells are typically in a dopey state of inertia, and they pretty much leave our tissues alone.

But at times, somnolent autoreactive B cells become activated, take aim at our own tissues and instigate one of the disorders collectively called autoimmunity. Some awakened autoreactive B cells crank out antibodies that bind to proteins and DNA inside the nuclei of our cells. Such activated “antinuclear antibodies” — the hallmark of lupus — trigger damage to tissues randomly distributed throughout the body, because virtually all our body’s cells have nuclei.

The vast majority of EBV-infected people (most of us, that is) have no idea they’re still sheltering a virus and never get lupus. But essentially everyone with lupus is EBV-infected, studies have shown. An EBV-lupus connection has been long suspected but never nailed down until now.

The antinuclear B cell gets ornery

Although latent EBV is ubiquitous in the sense that almost everybody carries it, it resides in only a tiny fraction of any given person’s B cells. As a result, until the new study, it was virtually impossible for existing methods to identify infected B cells and distinguish them from uninfected ones. But Robinson and his colleagues developed an extremely high-precision sequencing system that enabled them to do this. They found that fewer than 1 in 10,000 of a typical EBV-infected but otherwise healthy individual’s B cells are hosting a dormant EBV viral genome.

Employing their new EBV-infected-B-cell-identifying technology along with bioinformatics and cell-culture experimentation, the researchers found out how such small numbers of infected cells can cause a powerful immune attack on one’s own tissues. In lupus patients, the fraction of EBV-infected B cells rises to about 1 in 400 — a 25-fold difference.

It’s known that the latent EBV, despite its near-total inactivity, nonetheless occasionally nudges the B cell it’s been snoozing in to produce a single viral protein, EBNA2. The researchers showed that this protein acts as a molecular switch – a “transcription factor” – activating a battery of genes in the B cell’s genome that had previously been at rest. At least two of the human genes switched on by EBNA2 are recipes for proteins that are, themselves, transcription factors that turn on a variety of other pro-inflammatory human genes.

The net effect of all these genetic fireworks is that the B cell becomes highly inflammatory: It dons its “professional antigen-presenting cell” uniform and starts stimulating other immune cells (called helper T cells) that happen to share a predilection for targeting cell-nuclear components. These helper T cells enlist multitudes of other antinuclear B cells as well as antinuclear killer T cells, vicious attack dogs of the immune system.

When that militia bulks up, it doesn’t matter whether any of the newly recruited antinuclear B cells are EBV-infected or not. (The vast majority of them aren’t.) If there are enough of them, the result is a bout of lupus.

What comes next?

Robinson said he suspects that this cascade of EBV-generated self-targeting B-cell activation might extend beyond lupus to other autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and Crohn’s disease, where hints of EBV-initiated EBNA2 activity have been observed.

The million-dollar question: If about 95% of us are walking around with latent EBV in our B cells, why do some of us, but not all of us, get autoimmunity? Robinson speculates that perhaps only certain EBV strains spur the transformation of infected B cells into antigen-presenting “driver” cells that broadly activate huge numbers of antinuclear B cells.

Many companies are working on an EBV vaccine, and clinical trials of such a vaccine are underway. But that vaccine would have to be given soon after birth, Robinson noted, as such vaccines are unable to rid an already-infected person of the virus.

Stanford University’s Office of Technology Licensing has filed a provisional patent application on intellectual property associated with the study’s findings and technologies used to obtain them. Robinson, Younis and a third study co-author, Mahesh Pandit, PhD, a postdoctoral scholar in immunology and rheumatology, are named inventors on the application. They are co-founders and stockholders of a company, EBVio Inc., a company exploring an experimental lupus treatment, ultradeep B-cell depletion. This procedure involves total annihilation of all circulating B cells, which are replaced over the following few months by new, EBV-free B cells born continually in the bone marrow. Robinson is also a director of EBVio Inc. and a co-founder and shareholder of Flatiron Bio, LLC.

Source: Stanford Medicine