From Hospital Wards to Clinic Ownership, SA Nurses Are Becoming Their Own Bosses

“Mpathy Clinics are nurse-led, low-fee primary healthcare facilities with a vision of transitioning from nurse-led to nurse-owned clinics, creating opportunities for nurses to own and operate clinics in their own communities,” said Rhiza Ventures managing director Linda Dunkley.

For decades, nurses were the backbone of South Africa’s healthcare system, present in every ward, every emergency and every recovery room, but rarely in positions of ownership and leadership.

Now, as South Africa marks International Nurses Day on May 12 under the global theme “Empowered Nurses Save Lives”, a growing network of township clinics is transforming nurses from employees into entrepreneurs while helping to ease pressure on overcrowded public healthcare facilities.

Affordable Healthcare and Building Local Economies

In communities where patients often endure long queues at public clinics or cannot afford private healthcare, nurse-led Mpathy Clinics are emerging as an accessible and affordable alternative rooted in empowerment, dignity and community-based care.

The model, driven by NPO Rhiza Babuyile, currently operates 11 clinics in township areas including Umlazi, Naledi, Gugulethu, Tembisa and Diepsloot. Beyond expanding primary healthcare access, the initiative is creating something rarely seen in South Africa’s nursing

“South Africa’s public sector serves roughly 80% of the population, yet clinics routinely face long queues, staff shortages and medicine stockouts. Most primary healthcare services fall within the legal scope of a Professional Nurse and policies like NIMART (Nurse Initiated Management of Antiretroviral Treatment) – leaning on nurses is the only way to scale primary healthcare capacity at a cost the country can afford,” says Rhiza Ventures, Managing Director Linda Dunkley.

For Mpathy, this means helping the Department of Health extend healthcare services into underserved communities while aligning with the Ideal Clinic Realisation programme and supporting the long-term National Health Insurance (NHI) rollout, where accredited primary healthcare facilities serve as the first point of entry.

“Nurse-led PHC clinics like Mpathy are where early detection is possible, response rates are highest, and the cost to both the patient and the public system is lowest,” said Dunkley.

Dunkley added that the clinics were designed to complement, rather than compete with, the public healthcare system. “Mpathy is positioned explicitly as an extension of the Department of Health rather than a parallel system,” she said.

The clinics also contribute to local economic development, not only creating jobs for administrators and community health workers, but   enabling non-nursing entrepreneurs to own clinics and employ qualified nurses, broadening community-based healthcare investment and expanding access to care.

This month alone, a new Mpathy Clinic will open in Orange Farm on 21 May, led by nursepreneur Sister Mbalenhle, and on 19 May an entrepreneur will be inducted into the model in  Zithobeni, Bronkhorstspruit.

‘It’s My Answered Prayer’ — A Nurse Returns Home as Nursepreneur

For professional nurse and nursepreneur Sindiswa Nhlabathi, the model has become deeply personal.  Nhlabathi will this week open the  Mpathy Clinic in Naledi, Orange Farm on 14 May, serving the same community where she was born and raised.

“I was born at Zola, right across from where the Naledi clinic is based. I grew up in a family where no one was formally employed but they were ‘business people’,” she said. Her mother and grandmother sold cakes and goods to support the family. “It wasn’t easy as there was no money for university,” she said.

Before nursing, she worked at a government hospital as a personal assistant manager. Until a friend changed everything. “One day my friend came to me with nursing application forms and persuaded me to apply. I refused telling her that ‘you know I don’t like nursing’ but she insisted. I was accepted and the minute I was exposed to clinical experiments I knew I was born for this.”

After years in public healthcare, including at Zola Clinic, Nhlabathi resigned from her permanent post and was later offered the opportunity to run the Naledi clinic. “When I was studying it never crossed my mind that one day I might own a clinic. It’s my answered prayer. I feel empowered and I don’t even have the words to articulate my heart but one thing I know is that I intend to take this opportunity and make the best out of it,” says Nhlabathi.

At the clinic, children can receive treatment for under R200, while adult consultations with medication cost up to R350.

“Our clinic is private but very affordable,” Nhlabathi adds that “Our community relies on social grants and low incomes, while public clinics remain overwhelmed. Mpathy Clinics are a bridge between private and public healthcare and our priority is to build trusted relationships with the community.”

Visit https://mpathyclinic.co.za/ to find out more.

NHI Constitutional Court Arguments Hinge on Public Participation

Photo by Wesley Tingey on Unsplash

The Constitutional Court’s hearing over National Health Insurance (NHI) concluded on 7 May. The Board of Healthcare Funders (BHF) and the Western Cape Provincial Government made a combined application challenging the NHI Act on public participation grounds.

The Court is now deliberating; on such complex constitutional matters, it can be weeks to months before a judgment is made. The implementation of NHI remains suspended, following February’s High Court order – President Cyril Ramaphosa and the Minister of Health have formally undertaken not to proclaim or implement any part of the act until the Constitutional Court’s ruling. Other legal challenges are now paused.

What were the arguments?

The hearings focused on one key question: whether Parliament’s process met the constitutional threshold for public participation (primarily under Sections 59 and 72 of the Constitution). Section 59 mandates proactive, reasonable, and meaningful public engagement for the country’s participatory democracy. Formalities alone do not satisfy it – rather, the test is contextual reasonableness aimed at genuine influence. Constitutional Court challenges for national legislation are the main means by which Section 59 is enforced.

The BHF argued that hundreds of thousands of written submissions were effectively ignored; critical information was not provided; and whether, without such information, the test for rational law-making was met.

The Western Cape (led by Premier Alan Winde) focused primarily on deficiencies in the NCOP and provincial stages of the process, arguing that these violated constitutional public-participation requirements and undermined provincial roles. For example, the NCOP process was compressed into only eight weeks, key inputs were ignored, and provincial roles were undermined.

Parliament contended that the process was far more than a “tick-box” exercise, presenting the NHI to the public as a radical, transformative process and that details would only emerge as the project proceeded. [Nevertheless, even a simple calculation would show an NHI budget of R200bn, requiring crippling taxation.] They also argued that accommodations were made, such as extending written comment deadlines. They also argued that changes were made to the Bill, and that engagement does not mean that the legislature agrees, but rather is informed.

Judges raised questions about the integrity and practicality of the public health system in the context of NHI, but the core legal issue remained procedural compliance as opposed to the policy merits.

Is there precedent?

This would not be the first time the Constitutional Court has set aside Acts. In 2006, in a case brought by Doctors for Life, the Choice on Termination of Pregnancy Amendment Act and Traditional Health Practitioners Act were invalidated as Parliament had failed to comply with its section 72(1)(a) constitutional obligation to facilitate public involvement before passing.

Further cases reinforced that inadequate information, rushed timelines, and a lack of consultation over major changes would result in a breach. Parliament, however, argues that Doctors for Life shows that the requirement for participatory democracy has been met.

All parties now await the Court’s decision, which could either uphold the Act, declare it partially or wholly invalid, or remit aspects back to Parliament for correction.

Could an Asthma Medication Also Protect Against MASH?

Credit: Pixabay CC0

Join our podcast as we unpack a study exploring the potential of the asthma medication formoterol as a novel treatment for Metabolic Dysfunction-Associated Steatohepatitis (MASH), a severe liver condition often linked to diabetes.

The researchers used experiments involving high-fat diet mice and human liver cell cultures to show that this beta 2 adrenergic receptor agonist effectively reduces liver fat accumulation. It does so by stimulating mitochondrial biogenesis and enhancing metabolic efficiency. In addition, a massive retrospective analysis of nearly 60 000 patients revealed that those using long-acting versions of these drugs experienced significantly lower rates of liver complications and reduced mortality.

Honouring the Nurses that Give Their Heart into Saving Lives

Every day, across South Africa, nurses stand at the frontline of saving lives. They are the steady hands in moments of uncertainty, the compassionate voices during times of fear, and the dedicated professionals who work tirelessly to ensure that patients receive the care they need when it matters most.

As the world commemorates International Nurses Day 2026 under the theme “Our Nurses. Our Future. Empowered Nurses Save Lives,” the South African National Blood Service pays tribute to the remarkable nurses whose compassion, strength, and dedication continue to save lives every single day.

Behind every successful blood donation is a nurse who chose to care.

A nurse who arrives before sunrise. A nurse who comforts anxious donors with a smile. A nurse who stands for hours ensuring every unit of blood collected is safe enough to save a mother, a child, a trauma victim, or a cancer patient. These are the quiet acts of heroism that often go unseen, yet they change lives every day.

At SANBS, nurses are more than healthcare professionals. They are the heartbeat of the organisation’s lifesaving mission. They carry the emotional weight of the work with grace and continue to show up with compassion even on the hardest days.

Nurses carry the human side of healthcare. They give comfort in moments of fear and hope in moments of uncertainty. At SANBS, we see their sacrifices, their long hours, and the care they pour into every donor and patient. Today we honour them not only for what they do, but for who they are.” said Monique Schreiner, Senior Manager: Donor Relations.

Every drop of blood collected carries the fingerprints of a nurse who cared enough to make sure someone else gets another chance at life.

Whether working at donor centres, mobile clinics, community blood drives, or behind the scenes ensuring quality and safety, SANBS nurses continue to serve with unwavering commitment. Their work demands patience, emotional strength, skill, and empathy. Yet despite the pressure and responsibility they carry, they continue to give so much of themselves to others.

There is something deeply powerful about the work our nurses do. They stand beside people in vulnerable moments and remind them that humanity still exists through kindness and care. SANBS is proud to walk alongside these incredible professionals who continue to keep the spirit of service alive,” said Monique Schreiner, Senior Manager: Donor Relations.

International Nurses Day is a moment to pause and recognise the people who dedicate their lives to caring for others, often placing the needs of patients and donors before their own. It is a reminder that healthcare is not only built through medicine and technology, but through compassion, patience, and human connection.

This year’s theme speaks directly to the future of healthcare. Empowered nurses strengthen healthcare systems, uplift communities, and save lives. Their wellbeing and support matter because when nurses are valued, entire communities benefit.

For SANBS, celebrating nurses is deeply personal. These are the individuals who hold hands during difficult moments, calm fears with gentle words, and continue to give their all so that others may live.

To every nurse who continues to wear their uniform with pride, compassion, and courage, thank you.

Thank you for the sacrifices no one sees.
Thank you for the comfort you give so freely.
Thank you for keeping hope alive.
And thank you for helping keep the blood of life flowing across South Africa.

Stay connected with SANBS on social media:

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Health Organisations Lend Support in Hantavirus Cruise Ship Outbreak

Photo by Taha Yasir Yöney

Remaining passengers from the cruise ship MV Hondius, where an outbreak of hantavirus occurred, have now been evacuated after docking in Tenerife. So far, only three fatalities are reported, although the number of known infected cases has risen. Health organisations around the world are extending their support.

In a media briefing, Dr Tedros Adhanom Ghebreyesus, WHO Director-General said that eight cases have been reported so far, including three deaths. Five of the 8 cases have been confirmed as hantavirus.

According to the World Health Organization, the hantavirus in this case is the Andes virus, which is the only one capable of human transmission, albeit in an extremely limited fashion. Prolonged and close contact is required, as would happen on board a cruise ship.

Describing the situation, Dr Tedros said, “While this is a serious incident, WHO assesses the public health risk as low.” He noted that given the incubation period, “it’s possible that more cases may be reported.” Among medical support offerd, the WHO has distributed test kits from Argentina to five countries to support testing.

The US Centers for Disease Control has dispatched a medical team to the Canary Islands.

Prior to this incident, the most serious outbreak of Andes hantavirus was in Epuyén, Argentina, in late 2018 to early 2019 with 34 confirmed cases and 11 deaths (case fatality rate ~32%). Previously, very little was known about the Andes strain, explained Dr Gustavo Palacios, a microbiologist at Mount Sinai in New York, speaking to CNN.

“There is very limited experience handling this virus,” said Palacios, who had helped to trace how the virus spread. The study of the outbreak was published in 2020 in the New England Journal of Medicine.

“Probably we are having less than – I don’t know, I’m giving you a number, just for a ballpark number – 300 cases in history” of human to human transmission of Andes virus and about 3000 Andes cases overall, Palacios said.

Based on research into the Epuyén outbreak, Palacios said there seems to be only a roughly day-long window for transmission of the Andes virus of about a day, when patients first develop a fever.

Index case identified

The patients likely picked up the virus while they were on shore, before boarding the ship. The New York Post reports that Dutch ornithologist, Leo Schilperoord, was patient zero for the hantavirus outbreak. Along with his wife Maria Schilperoord, he visited a landfill outside of the city of Ushuaia to seek out a rare bird – birdwatchers frequent the landfill due to the number of birds flocking there. Argentinian authorities believe that it was there that he came in contact with long-tailed pygmy rats, inhaling particles of its faeces, which carries the Andes strain.

After boarding the ship with 112 others – including many other birdwatchers and scientists – he fell ill with diarrhoea and abdominal pain on April 6 and dying five days later. His wife was flying back with his body but collapsed when connecting in Johannesburg, and died in hospital the next day. Meanwhile, the UK man who was in intensive care in a Johannesburg hospital is now making a recovery.

Viatris Expands Nurse-owned Clinics in Partnership with Rhiza Babuyile Recognising Nurses’ Key Role in Sustainable Healthcare Access

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As demand for healthcare services continues to grow in South Africa, scalable, community-based healthcare models are playing an increasingly important role in improving access to care.

Viatris Inc. (Nasdaq: VTRS), a global healthcare company, commenced its partnership with South African non-profit organisation Rhiza Babuyile in 2020 to support scalable, community-based models that bring care closer to patients. This includes a growing network of nurse-led clinics, which are helping to close critical access gaps while strengthening local healthcare capacity.

Today, six clinics supported by Viatris, across South Africa and Sub-Saharan Africa, are operational, forming part of a broader network of community-based healthcare programmes that collectively reach thousands of patients annually.

This expansion reflects Viatris’ broader global ambition to deliver sustainable access to healthcare at scale – ensuring that patients, regardless of geography, can access the medicines and services they need. This ambition reflects Viatris’ mission to empower people worldwide to live healthier at every stage of life.

“Across the world, healthcare systems are under increasing pressure, and the need for sustainable, scalable solutions has never been greater,” said Arvind Kanda, Head of ARV/API SA and SSA. “Our focus is on building healthier communities by expanding access to medicines, and empowering healthcare providers, especially nurses, who are essential to delivering care. By supporting locally driven models that provide care directly to communities, we can help build stronger, more resilient health systems for the future.”

This International Nurses Day, Viatris is recognising the vital role nurses play in expanding access to quality, sustainable healthcare – particularly in underserved communities where they are often the first and most trusted point of care.

In South Africa, nurses form the backbone of the healthcare system, accounting for approximately 80% of the country’s healthcare workforce and serving as the primary point of care for millions of patients[i]. This makes their role in community-based care models not only essential, but transformative. Globally, nurses represent the largest segment of the health workforce and are indispensable in addressing inequities in access to care – a role that is especially critical in underserved communities.[ii]

One such example is Sr. Nompumelelo Mudalahothe, who began her journey as a nurse at the Rhiza Babuyile Diepsloot clinic and has since progressed to become a healthcare manager overseeing the Mpathy nursepreneur clinics. Her journey reflects how investing in nurse-led models can unlock both improved patient outcomes and meaningful career pathways.

She says, “In many communities, nurses are the first, and sometimes only, point of access to healthcare.” She also explains that she became a nurse to make a difference in people’s lives: “Working in my own community allows me to do that every day. The clinic is more than just a place to get treatment, it’s a place where they feel heard, supported and understood.”

Rhiza Babuyile founder and board member Alef Meulenberg says one such example is when a patient brought a 4-month-old baby to the clinic. “The baby was non-responsive and would have died. Our nurse was already on her way home, but opened the clinic, stabilised the baby and afterwards referred the patient to a nearby hospital for further treatment. This baby is now fortunately doing well and has the chance for a long, healthy life.”

The clinics themselves continue to evolve, expanding beyond primary healthcare to offer services such as chronic disease management and access to chronic medication, as well as optometry services and, in one facility, x-ray capabilities. These integrated services are critical in addressing the growing burden of non-communicable diseases and improving continuity of care at community level.

Viatris’ approach is grounded in its long-term vision to be a trusted healthcare partner – one that combines global expertise with local insight to improve health outcomes and expand access in a meaningful, sustainable way. As the company continues to evolve its portfolio and strengthen its global footprint, this commitment remains central to its path forward.


[i] Abrahams, F. (2025). Assessing the composition of nurses in South Africa versus global standards. International Journal of Africa Nursing Sciences.

[ii] World Health Organization (2020). State of the World’s Nursing 2020: Investing in Education, Jobs and Leadership

What Factors are Involved in the Co-occurrence of Autism in Children with Epilepsy?

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Children with epilepsy have a higher risk of also having autism spectrum disorder (ASD). A new study in Developmental Medicine & Child Neurology examined factors associated with the co-occurrence of autism and epilepsy in a large population-based group.

For the study, investigators at the Mayo Clinic compared the prevalence of autism spectrum disorder in children with and without epilepsy based on medical records, and they evaluated associated factors including sex, age at autism identification, and intellectual disability. The study included 30 490 children in the Olmsted County, Minnesota birth cohort, of whom 257 (0.84%) had epilepsy diagnosed before 19 years of age.

Autism prevalence was significantly higher among children with epilepsy as compared with children without across all three research and clinical definitions assessed (21.4% versus 3.2% using broad research criteria, 14.0% versus 1.6% using stricter research criteria, and 7.9% versus 0.7% for clinical diagnosis).

Children with epilepsy and autism were more likely to have intellectual disability (56.5% versus 15.4%), were more often female (38.2% versus 25.8%), and were identified with autism at a younger age (7.4 versus 8.7 years) compared with those without autism.

“These observations highlight clinically relevant differences within this group and underscore the importance of early recognition of developmental concerns,” said lead author Mariya Saify. MBBS.

Senior author Elaine C. Wirrell, MD added that although children with epilepsy are at an elevated risk of autism, recognition can be delayed. “Our findings emphasise the importance of screening for autism in this population to support earlier diagnosis and timely intervention, both of which are key to improving long-term outcomes.”

Source: Wiley

New Drug with Fewer Side Effects Reduces Breast Density

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Low doses of the investigational medicinal product endoxifen reduce breast density to the same extent as the standard treatment tamoxifen, but without causing such troublesome side effects. These are the findings of a new study from Karolinska Institutet which appears in the Journal of the National Cancer Institute. The results may have implications for future preventive treatment of breast cancer.

Tamoxifen is a well-established drug that has been used for more than 40 years to reduce the risk of recurrence in patients with breast cancer. The drug is also approved for prevention of breast cancer in women at increased risk.

However, the side effects of tamoxifen are a major problem. Many women experience menopausal-like symptoms, such as hot flushes, which means that many do not complete the treatment.

Endoxifen is the most active metabolite formed when tamoxifen is broken down in the body. The new study investigated whether endoxifen in tablet form could provide the same biological impact and a more predictable effect than tamoxifen.

A total of 240 healthy, premenopausal women were randomised to receive a placebo or 1 or 2 mg of endoxifen daily for six months. The researchers then measured mammographic breast density. High mammographic density can contribute to an increased risk of breast cancer but a reduction during treatment can be a good measure of therapeutic outcome.

”Both 1 and 2 milligrams of endoxifen resulted in a clear reduction in breast density compared with the placebo,” says Mattias Hammarström, co-author and PhD candidate at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet.

The results show that 1mg of endoxifen reduced breast density by an average of 19% and 2mg by 26%. Data from a previous study show that 20mg of tamoxifen reduces density by approximately 18.5%. The effect of low-dose endoxifen thus corresponded to that seen with tamoxifen.

Participants who received 2mg of endoxifen reported a greater worsening of hot flushes and night sweats compared with the lower-dose group, whilst the 1 mg group had a safety profile similar to that of the placebo with respect to serious side effects and biomarkers.

”Our results suggest that a lower dose may be sufficient to affect breast density, whilst also appearing to be better tolerated,” says Mattias Hammarström.

The study is a so-called proof-of-concept trial, meaning it is designed to demonstrate that a treatment produces the expected biological effect before larger and longer trials are conducted. However, the study cannot show whether endoxifen reduces the risk of breast cancer or recurrence.

Source: Karolinska Institutet

One Molecule, Two Effects: A New Drug Concept to Treat Obesity and Type 2 Diabetes

Photo by Nataliya Vaitkevich on Pexels

A team led by metabolism researcher Prof Timo D. Müller at Helmholtz Munich has developed a new approach for treating obesity and type 2 diabetes: a hybrid molecule uses the well-known GLP-1/GIP signalling pathway as a “door opener” and delivers an additional metabolic modulator specifically into the target cells. In laboratory experiments, mice subsequently ate less, lost more weight and showed improved blood glucose values compared with reference treatments. The researchers published their preclinical results in the journal Nature.

Modern incretin therapies – drugs that mimic the body’s own satiety and blood-glucose signals (GLP-1/GIP) – have markedly improved the treatment of obesity and type 2 diabetes. Yet a key challenge remains: physicians would like to use further metabolic “levers”, for example drugs that make cells more responsive to insulin, so that glucose moves more easily from the blood into tissues. However, such additional drugs often act system-wide rather than in a targeted manner, increasing the risk of side effects.

“Our guiding question was: how can we enhance incretin activity without creating a second, systemically active source of side effects?” says the study lead Timo D. Müller, Director of the Institute for Diabetes and Obesity (IDO) at Helmholtz Munich, Professor at the Ludwig Maximilian University of Munich (LMU) and researcher at the German Center for Diabetes Research (DZD). 

Müller’s team therefore pursued the idea of an “address label with cargo”: the researchers chemically linked a well-established incretin active component to a second pharmacological component – the drug lanifibranor, a so-called pan-PPAR agonist. The incretin part binds to GLP-1 or GIP receptors on the cell surface and ensures that the hybrid molecule is taken up into the cell. Inside the cell, the second component binds to PPARs – “switches” in the cell nucleus that regulate genes involved in fat and sugar metabolism. The aim is for this additional metabolic effect to arise specifically in GLP-1R/GIPR- expressing cells, rather than throughout the body.

Low Dose via a “Trojan Horse”

Functionally, the hybrid molecule combines five drug targets in one: it activates two receptors on the cell surface (GLP-1R and GIPR) and additionally engages three PPAR “switches” inside the cell. Müller describes the principle as a “Trojan horse”: the incretin part opens the door; the “cargo” acts only once it is inside the target cell. “A major advantage is the amount,” says Müller. “Because the second component is not administered separately and systemically, but ‘travels along’ with the incretin part, it can be used at a dose that is orders of magnitude lower.” In this way, the drug gains efficacy without amplifying side effects through broad distribution across the body.

In laboratory mice with diet-induced obesity, the approach showed clear effects: “The animals ate less and lost more weight than under a GLP-1/GIP co-agonist without cargo,” says Dr Daniela Liskiewicz, group leader at IDO and co-first author together with Dr Aaron Novikoff. “In the head-to-head comparisons shown, the effect was in part even stronger than with a GLP-1-only drug.” The study therefore suggests that the coupling is not merely “more of the same”, but measurably strengthens incretin activity – at least in mice.

Additional Metabolic Readouts Improve

It was not only body weight that changed: in the experiments, blood-glucose values improved and there were indications of better insulin action in the body. Put simply, insulin was better able to “channel” glucose from the blood into tissues, and the liver released less glucose into the bloodstream. At the same time, the researchers report that typical gastrointestinal side effects were comparable in their assessment to those of existing incretin therapies – and that, in the parameters examined, they found no indications of two feared issues associated with the coupled component, namely fluid retention and anaemia.

Beyond glucose metabolism, the mouse data also provided indications of additional, potentially favourable effects on the heart and liver. It is important to note that this is a preclinical study: whether the results will translate to humans remains open – also because the GIP receptor differs between mice and humans. “We see a principle with strong effects in the animal model – now the task is to optimise the approach for humans and move it towards the clinic,” says Müller. For that development, strong industry partners will be needed, he adds.

Source: Helmholtz Association of German Research Centres

T Cells, not B Cells, Are the Culprit of Kidney Damage in Lupus

Chronic kidney disease (CKD). Credit: Scientific Animations CC4.0

Kidney damage is a serious complication affecting individuals with lupus, an autoimmune disease where immune B cells malfunction and produce antibodies that attack the body’s own cells, tissues, and organs.

B cells, when they make autoantibodies, have been blamed for the illness, prompting the development of several FDA-approved medications that target them. However, lupus nephritis is inevitable in more than half of patients with lupus and B cell depletion is often ineffective therapeutically.

Now, in a study published April 20 in ImmunityYale scientists have found that the kidney damage culprit is actually a specific T cell – the CD8 T cell.

“People have been, to some extent, ignoring CD8 T cells because of their focus on B cells and the production of autoantibodies,” says lead author Jafar Al Souz, an MD-PhD student in the lab of Joseph Craft, MD, Paul B. Beeson Professor of Medicine (Rheumatology) and professor of immunobiology at Yale School of Medicine. “But we need to think more deeply about why current therapies fail in some patients.”

T cells drive kidney damage in lupus

Previous work in the Craft Lab has shown that blocking T cells’ activity in mouse models of lupus could spare the animals from kidney injuries. That result prompted Al Souz to look closer at this subset of the immune cells.

“What I saw was that these T cells in the sick kidney had a killer phenotype; they were very activated with the potential to cause kidney damage,” he says. Nearly all of these cells were CD8 T cells – also known as cytotoxic T lymphocytes – which are generally tasked with identifying and killing pathogens. That they are aggravated in the kidneys of mouse models of lupus shows that the cells see the kidney as a foreign invader that needs to be destroyed, Al Souz says.

He also found that when the CD8 T cells were depleted, the kidney function was maintained.

Using single-cell multiomics, a high-resolution technique to simultaneously measure the various molecular characteristics of a cell, analysing simultaneous RNA production, gene regulation, and T cell identity, the researchers pinned down the origin of the CD8 T cells to the renal lymph nodes.

“What gave us the biggest clue was that the CD8 T cells in the kidney had very strong overlap with the cells in renal lymph nodes,” Al Souz says. T cells normally undergo rapid proliferation, where one T cell multiplies and generates identical offspring that target the same antigen proteins. “We know that once a T cell is activated in renal lymph nodes, it will leave, go to the circulation and then enter kidneys. So, the fact that we saw identical T cells in renal lymph nodes, circulation, kidneys tells us that the lymph nodes were actually the site of origin.”

What is unique about these CD8 T cells is their capacity to self-renew like stem cells, a discovery that sheds light on a long-held mystery of why it’s hard to stop treatment in patients with lupus. “Constant therapy is needed because these CD8 T cells in the lymph nodes continually supply the kidney with T cells that can damage the organ,” says Craft, who is also the director of the Colton Center for Autoimmunity at Yale.

Targeting T cells for treatment

To draw parallels in humans, the researchers used single-cell RNA sequencing to analyse biopsies from 156 patients with lupus nephritis and 30 healthy individuals. Just as they found in mice, the researchers identified kidney-infiltrating CD8 T cells with the stem-like property in the patients. Unlike in healthy individuals, there was a significantly higher proportion of CD8 T cells that were always active and ready to cause damage in the patients’ kidneys.

“Generally, CD8 T cells are good at pumping the brakes and limiting damage potential upon chronic activation. But we found that in lupus, even when molecules that should stop these T cells from damaging healthy cells are present, it didn’t make the T cells lose function and the capacity for kidney injury,” Al Souz says.

The tendency for T cells to attack a person’s own cells is a typical autoimmune response. For example, in type 1 diabetes – an organ-specific autoimmune disease – T cells mistakenly recognise pancreatic beta cells as foreign and destroy them, thereby stopping insulin production. In cancer and chronic diseases, the ability for T cells to replenish could be beneficial, leading to the elimination of pathogens and tumours. However, the role of T cells in systemic autoimmune diseases like lupus has not been fully described.

“Our results show that there’s more to it than what we understand,” Al Souz says.

By identifying the real culprit, the researchers hope that future treatment of lupus nephritis will be more targeted. “The first step is knowing that it’s abnormal in the first place,” Craft says. “Now, we can think about strategies to lower the number of active CD8 T cells back to the normal range.”

By Kristel Tjandra

Source: Yale School of Medicine