Identical twins light the way for new genetic cause of arthritis

Identical twin girls who presented with severe arthritis helped scientists to identify the first gene mutation that can single-handedly cause a juvenile form of this inflammatory joint disease. By investigating the DNA of individual blood cells of both children and then modelling the genetic defect in a mouse model, the research team led by Adrian Liston (VIB-KU Leuven) was able to unravel the disease mechanism. The findings will help to develop an appropriate treatment as well.

Juvenile idiopathic arthritis is the most common form of all childhood rheumatic diseases. It is defined as arthritis that starts at a young age and persists throughout adulthood, but which does not have a defined cause. Patients present with a highly variable clinical picture, and scientists have long suspected that different combinations of specific genetic susceptibilities and environmental triggers drive the disease.

A single gene mutation

In a new study by researchers at VIB, KU Leuven and UZ Leuven, the cause of juvenile arthritis in a young pair of identical twins was traced back to a single genetic mutation.

"Single-cell sequencing let us track what was going wrong in every cell type in the twin’s blood, creating a link from genetic mutation to disease onset,” explains Dr. Stephanie Humblet-Baron, one of the researchers involved in the study. “It was the combination of next generation genetics and immunology approaches that allowed us to find out why these patients were developing arthritis at such a young age.”

Of mice and men

Parallel studies in mice confirmed that the gene defect found in the patients’ blood cells indeed led to an enhanced susceptibility to arthritis. Prof. Susan Schlenner, first author of the study, stresses the relevance of this approach: "New genetic editing approaches bring mouse research much closer to the patient. We can now rapidly produce new mouse models that reproduce human mutations in mice, allowing us to model the disease of individual patients."

According to immunology prof. Adrian Liston such insights prove invaluable in biomedical research: “Understanding the cause of the disease unlocks the key to treating the patient.”

From cause to cure

Liston’s team collaborated closely with prof. Carine Wouters, who coordinated the clinical aspect of the research: "The identification of a single gene that can cause juvenile idiopathic arthritis is an important milestone. A parallel mouse model with the same genetic mutation is a great tool to dissect the disease mechanism in more detail and to develop more effective targeted therapies for this condition.”

And the little patients? They are relieved to know that scientists found the cause of their symptoms: "We are delighted to know that an explanation has been found for our illness and more so because we are sure it will help other children."

Thankfully, the children’s arthritis is under good control at the moment. Thanks to the new scientific findings, their doctors will be in a much better position to treat any future flare-ups.

NFIL3 mutations alter immune homeostasis and sensitise for arthritis pathology 

Schlenner et al. 2018 Annals of the Reumatic Diseases

Stephanie Humblet-Baron tackles one immune disease after the other

In two recent studies, the same team of scientists has uncovered the mechanisms underlying two distinct immunological disorders affecting both children and adults. Stephanie Humblet-Baron(VIB-KU Leuven) was the researcher at the helm of both projects.

A pediatrician by training, Stephanie Humblet-Baron is building a career unravelling immunological disorders that affect children. She divides her time between the clinic and the lab, where she is a senior team leader in the lab of Adrian Liston (VIB-KU Leuven).

From disease to biology and back again

Ever since the start of her medical training, Humblet-Baron developed a special interest in unraveling the biological mechanisms that cause immunological problems. Many immune diseases are poorly understood, and this lack of knowledge also limits treatment options and choices.

“People sometimes refer to these diseases as rare,” says Humblet-Baron, “but we all carry risk factors for many immunological diseases. Even if a given mutation is rare, the accumulated variation in immunological responses affect a broad set of outcomes, for example how someone responds to cancer treatment or drugs for cardiovascular conditions. That is why understanding the mechanisms underlying immune-dysregulation is so important.”

In her most recent work, Humblet-Baron, together with her colleagues in the lab of Adrian Liston (VIB-KU Leuven), focused on the mechanisms causing myeloproliferative disease and hemophagocytic lymphohistiocytosis, two diseases that are fatal unless given aggressive treatment.

Myeloproliferative disorder: a partner in crime for dendritic cells

Dendritic cells are specialized antigen-presenting cells that play a crucial role in coordinating innate and adaptive immune responses. In both patients and mice, depletion of dendritic cells leads to myeloproliferative disorder, but how or why—no one really knew.

“To understand what was going wrong, we created a mouse model where dendritic cells were present in normal numbers, but were functionally impaired,” explains Humblet-Baron. “We found that without the antigen-presenting capacity of dendritic cells, the mice developed myeloproliferative disorder.”

The team uncovered that it was not the number of dendritic cells, but their partnership with CD4 T cells of the immune system that was crucial for disease development. When CD4 T cells were absent as well, the mice showed no symptoms of myeloproliferative disease.

This has important implications for patients, where specific mutations also manifest both dendritic cell deficiency and myeloproliferative disorder. “Based on the original model disease model, the proposed line of treatment would be dendritic cell replacement, currently only possible through bone-marrow transplantation,” says prof. Adrian Liston. “But these new results indicate that attenuating the activatory signal from CD4 T cells could also reduce the development of myeloproliferative disorder.”

Hemophagocytic lymphohistiocytosis: New light on a deadly disease

Hemophagocytic lymphohistiocytosis, HLH for short, is a severe disease less than 2 out of 3 patients survive. It can be triggered by a variety of factors, including genetic defects, viral infections, anti-tumor responses or unchecked autoimmunity. Excessive production of interferon γ was assumed to be the key pathological step, but based on patient evidence and a pre-clinical mouse model of the disease, the Leuven research team has now found that there is much more to it.

Humblet-Baron: “We found that the production of interferon γ was only responsible for part of the features of the disease. Excessive consumption of the immune signaling molecule interleukin 2 by hyperactivated CD8 T cells, the suppressor cells of our immune system, had a much greater impact on the inflammation.”

This means that at least two different disease pathways are at play—knowledge that indicates that we could save the lives of more patients if we also targeted both pathways during treatment.

“This study not only provides a new paradigm for understanding HLH, with major implications for its treatment, but also gives us a broad insight into how hyperactivated CD8 T cells cause damage,” adds prof. Adrian Liston.

“We can learn so much from an in-depth analysis of the immune cells present in a simple sample of blood from patients,” concludes Humblet-Baron, who hopes to uncover the mechanisms underlying many more of these immunological problems. “Coupled with the power of biochemical and animal research, these insights are really changing how we diagnose and treat patients in the clinic.”

—
Humblet-Baron, et al 2018 Blood. "Murine myeloproliferative disorder as a consequence of impaired collaboration between dendritic cells and CD4 T cells"

Humblet-Baron et al. 2018 Journal of Allergy and Clinical Immunology. "IFN-γ and CD25 drive distinct pathological features during CD8 T cell hyperactivation in hemophagocytic lymphohistiocytosis"

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Unlocking The Secrets Of A Rare Immune Disease

by Adrian Liston and Josselyn Garcia-Perez 

Primary immunodeficiencies (PID) are a heterogeneous group of disorders that disturb the host’s immunity, creating susceptibility to infections. PIDs are genetically diverse, with mutations in many different genes capable of causing immunodeficiency. The clinical symptoms of PIDs include, but are not limited to, susceptibility to infections, inflammation, and autoimmunity, although each gene mutated, and indeed each individual mutation, can lead to different manifestations.

Central to understanding PIDs is to understand which immune cell type is rendered defective by the mutation the patient carries. The type of infections the patient develops is often a key indicator of the underlying immunodeficiency; for example, pulmonary infections and bacterial septicemia are associated with B cell defect, whereas fungal susceptibility is associated with defects in certain types of T cells. Candidate pathways can be investigated using genetics and immune screening, and successful identification of the underlying causes allows a treatment program to be tailored to the patient.

Read the full story on Science Trends

Translational Immunology lab in the news

Our research was featured tonight on VRT News:

Speaking roles by Carine Wouters, Erika Van Nieuwenhove and Adrian Liston. Cameos from Stephanie Humblet-Baron, John Barber and Pier-Andree Penttila

 

 

Original research: Van Nieuwenhove et al. 2018 Journal of Allergy and Clinical Immunology. "A kindred with mutant IKAROS and autoimmunity"

If you would like to support our clinical research, and allow us to take on more cases like these, you can make a tax-deductable donation the Ped IMID fund, by transferring to IBAN-number BE45 7340 1941 7789, BIC-code: KREDBEBB with the label "voor EBD-FOPIIA-O2010".

Scientists uncover new genetic cause of lupus on World Lupus Day

A team of scientists and clinicians has identified a novel mutation causing an unusual form of the autoimmune disease lupus. The genetic analysis of a Belgian family sheds new light on the disease mechanisms underlying lupus, which could possibly yield new therapeutic approaches for patients. The findings are published in the Journal of Allergy and Clinical Immunology in the week leading up to World Lupus Day.

Lupus is an autoimmune disorder, meaning that the body’s immune system mistakenly attacks its own tissues. Lupus can affect multiple organs but its cause is often not clear. Usually a combination of genetic and environmental factors is at play.

Researchers in Leuven have now discovered a novel genetic mutation in a patient that presented at the age of 12 with both lupus and problems in the ability of the immune system to fight common infections. This unusual combination of symptoms was quite puzzling.

By analyzing the patient’s DNA and that of the parents, the scientists could trace the problem down to a specific mutation in the so-called Ikaros gene. This gene encodes the Ikaros protein that in turn binds DNA to affect the expression of other proteins.

Erika Van Nieuwenhove, clinician and scientist at VIB-KU Leuven, explains how the mutation caused the patient’s immune system to be hyperactive: “Because of the mutation, Ikaros can no longer bind its target DNA properly. We also observed that certain immune cells of the patients were hyperactive, even in the absence of stimulation. The link between both observations turned out to be CD22, a protein that normally dampens the immune response. In normal conditions, Ikaros stimulates the expression of this inhibitor, but this was not the case in this patient.”

About 5 million people worldwide have lupus, but a causative mutation in Ikaros is very rare. “Small changes in Ikaros are associated with susceptibility to adult-onset lupus, but because the effects are weak it is hard to work out what Ikaros is doing to the immune system,” explains prof. Adrian Liston (VIB-KU Leuven), who heads the lab for translational immunology and is lead author of the study. “In this particular family, however, a mutation created a large change in Ikaros, causing early-onset lupus. The mutation was strong enough to allow us to work out how changes in Ikaros cause lupus and immune deficiency.”

Although the patient in this study has a very rare form of lupus, the discovery nevertheless helps to map the overall disease mechanisms, underscores prof. Carine Wouters, pediatric rheumatologist at University Hospitals Leuven and co-lead of the study: “The mechanism we uncovered in this patient could also be meaningful in a different context with other patients. Now that we understand what goes wrong in this particular case, it could help us think of better targeted treatments for others as well.”

Original research: Van Nieuwenhove et al. 2018 Journal of Allergy and Clinical Immunology. "A kindred with mutant IKAROS and autoimmunity"

If you would like to support our clinical research, and allow us to take on more cases like these, you can make a tax-deductable donation the Ped IMID fund, by transferring to IBAN-number BE45 7340 1941 7789, BIC-code: KREDBEBB with the label "voor EBD-FOPIIA-O2010".

Nieuwe genetische oorzaak van lupus ontdekt

Leuvense artsen en onderzoekers ontdekken een DNA-fout die een ongewone vorm van de auto-immuunziekte lupus kan veroorzaken. Door het DNA van een jonge patiënt en diens ouders na te gaan slaagden ze erin het ziektemechanisme beter te belichten, wat op termijn tot betere behandelingsmogelijkheden zou kunnen leiden, ook voor andere patiënten. De resultaten werden vlak voor Wereld Lupusdag gepubliceerd in het vakblad ‘Journal of Allergy and Clinical Immunology’.

Lupus is een auto-immuunziekte die verschillende organen kan aantasten. Het afweersysteem maakt hierbij antistoffen aan tegen het eigen lichaam. De oorzaak is in veel gevallen onduidelijk, vaak speelt er een combinatie van zowel erfelijke als omgevingsfactoren.

Leuvense onderzoekers ontdekten nu een nieuwe genetische mutatie bij een patiënt die al op 12-jarige leeftijd lupus kreeg, maar tegelijkertijd ook heel weinig antistoffen aanmaakte om zich te beschermen tegen infecties. Deze ongewone combinatie van symptomen vormde een raadsel voor de artsen.

Dankzij een speurtocht in het DNA van de patiënt en van beide ouders, kon het team van wetenschappers de oorzaak herleiden naar een specifieke fout in het gen voor Ikaros. Dit gen is de blauwdruk voor een eiwit dat op zijn beurt aan DNA kan binden om de productie van andere eiwitten te stimuleren.

Erika Van Nieuwenhove, arts-onderzoeker aan VIB-KU Leuven, verduidelijkt waarom de drempel voor activatie van het afweersysteem daardoor zo laag is bij deze patiënt: “Door de fout in het gen kan Ikaros niet meer goed aan het DNA binden. We zagen ook dat bepaalde immuuncellen van de patiënt hyperactief waren, zelfs zonder stimulatie. De link tussen beide was het CD22 eiwit, dat normaalgezien de immuunreactie tempert. Ikaros stimuleert normaal de productie van deze demper, maar dus niet bij deze patiënt.”

Lupus bij kinderen komt relatief vaak voor, maar dat de oorzaak bij het Ikaros eiwit ligt is heel zeldzaam. “Kleine wijzigingen in Ikaros verhogen de kans op lupus bij volwassenen, maar omdat de effecten zo klein zijn was het aanvankelijk moeilijk om uit te vissen hoe Ikaros het immuunsysteem beïnvloedt,” vertelt professor Adrian Liston (VIB-KU Leuven), die aan het hoofd van het labo voor translationele immunologie staat. “Bij deze familie gaat het om een genetische wijziging met grotere gevolgen, die dan ook al op jonge leeftijd lupus veroorzaakt. Maar net door het grotere effect konden we nu uitklaren op welke manier het defecte Ikaros de immuunreactie verstoort.”

Hoewel het gaat om een zeldzame vorm van lupus helpt deze doorbraak om het hele plaatje beter in kaart te brengen, bevestigt Prof. Carine Wouters, kinderreumatoloog aan UZ Leuven, die samen met prof. Liston de studie leidde: “Het mechanisme dat we bij deze patiënt ontdekten kan ook een rol van betekenis spelen bij andere patiënten. Nu we bij deze persoon begrijpen wat er fout loopt kan dat ook helpen om voor anderen meer gerichtere therapieën te ontwikkelen.”

World Primary Immunodeficiency Week

This week is World Primary Immunodeficiency week. Primary immunodeficiencies (PID) are a cluster of rare immunological diseases, caused by genetic defects in any one of dozens of immunological diseases. The diseases are highly diverse at both a genetic and clinical level, ranging from immunodeficiency to multiple autoimmune manifestations to autoinflammatory manifestations. Typically, the diseases are caused by Mendelian mutations creating a specific defect in a single immunological checkpoint. Key problems in the field have been identifying the gene of interest (as many of the disorders show clinical heterogeneity and overlap) and identifying the immunological checkpoint that is disturbed.  

While gene discovery had been previously limited by the need for large affected families or distinct clinical presentations across multiple families (for classical genetic mapping), the advent of next generation sequencing gave rise to the possibility that even single families could be investigated. In 2010 we set up a large-scale immunogenetics study on PID patients from the clinic in Leuven.

The PID research program that we run has led to the mechanistic understanding of multiple new gene- disease associations. Results include the identification of Olmsted syndrome as an immunological as well as a dermatological disorder (Danso-Abeam et al, Orphanet Journal of Rare Diseases, 2013), STAT2 deficiency as a cause of severe viral childhood disease (Moens et al, Journal of Allergy and Clinical Immunology, 2017), IKAROS and IFIH1 mutations as a cause of juvenile systemic lupus erythematosus (Van Eyck et al, Arthritis and Rheumatology, 2015; Van Nieuwenhove et al, Journal of Allergy and Clinical Immunology, in press), and Roifman Syndrome as a disease of defective B cell development (Heremans et al, Journal of Allergy and Clinical Immunology, 2018). We have also identified novel treatments through this approach, such as in deficiency in adenosine deaminase 2 (DADA2, frequency unknown), which we independently identified and found to be cured by hematopoetic stem cell transplantation (Van Eyck et al, Journal of Allergy and Clinical Immunology, 2015). Several examples of this work deserve extra attention:

One of the major successes of this program was the identification of a new PID, Pyrin-associated neutrophilic dermatosis (PAAND). The study started with a single large family in Flanders who manifested a severe inflammatory skin condition. Through using our genetic screening approach we identified a mutation in MEFV, the gene encoding Pyrin. MEFV mutations had previously been associated with a different PID, Familial Mediterranean Fever (FMF, affects 1 in 1000 individuals in Mediterranean groups). Different mutations in the same gene were driving PAAND and FMF, with clinically distinct outcomes. We found that the PAAND mutation had destroyed a key immunological safety switch on the inflammasome (the multi-protein complex that initiates inflammation). In the absence of this safety switch, small triggers could drive the production of the inflammatory cytokine IL-1 (Liston and Masters, Nature Reviews Immunology, 2017). Returning to the clinical setting, we identified additional families with the disease and found that we could successfully treat the inflammation with recombinant IL-1 antagonist (Masters et al, Science Translational Medicine, 2016). We are now leading further multi-centred clinical trials on this disease.

Another PID we have worked on is Familial hemophagocytic lymphohistiocytosis (FHL). The genetic origin of FHL is largely known, with defects in the perforin pathway by which cytotoxic CD8 T cells kill viruses. Before our work, the general model for FHL disease mechanism was that certain viruses were difficult to control without perforin, leading to excessive viral titres. The compensatory increase in the cytokine interferon gamma would then drive the inflammatory and haematological symptoms of the disease. Using mouse models that mimic the disease, we demonstrated that while interferon gamma certainly increases to very high levels, this cytokine was only driving the haematological symptoms and was not responsible for the fatal inflammatory symptoms. Instead, the disease mechanism is driven by the hyper-activation of CD8 T cells leading to the “theft” of a cytokine called IL-2, which normally feeds an anti-inflammatory T cell population known as regulatory T cells. In both mice and humans with FHL, this theft leads to a dramatic loss of regulatory T cells and drives the inflammatory aspects of the disease (Humblet-Baron et al, Journal of Allergy and Clinical Immunology, 2017 and in press, Liston and Gray, Nature Reviews Immunology 2015). This work has opened up a new target for therapeutic intervention for this disease.

A seemingly paradoxical PID is leaky severe combined immunodeficiency (leaky SCID) which combines both immunodeficiency and excessive immune activation. Having developed a model to account for this paradoxical combination (Siggs et al, Immunity 2007; Liston et al, Nature Reviews Immunology 2008), we sought to direct test the model in mice. We developed a new mouse model for leaky SCID and found that, as predicted, the immune activation features were caused by a deficiency in regulatory T cell functions. Further, we found that these symptoms could be abrogated through the treatment of abatacept, an approved treatment for rheumatic arthritis (Humblet-Baron et al, Journal of Allergy and Clinical Immunology 2017). As abatecept is already approved for clinical use, this approach could immediately move into clinical trials.

We are now working on many more cases of suspected PID in the clinic, and hope to make more major breakthroughs in the near future!

If you are worried that your child may have a primary immunodeficiency, take a look at the Jeffrey Modell Foundation site, which outlines the warning signs and will help you find an expert.

If you would like to support our clinical research, and allow us to take on more cases like these, you can make a tax-deductable donation the Ped IMID fund, by transferring to IBAN-number BE45 7340 1941 7789, BIC-code: KREDBEBB with the label "voor EBD-FOPIIA-O2010".

New insights in genetic defect allow prevention of fatal illnesses in children

A team of scientists led by prof. Adrian Liston (VIB–KU Leuven) and prof. Isabelle Meyts (UZ Leuven – KU Leuven) were able to characterize a new genetic immunodeficiency resulting from a mutation in a gene named STAT2. This mutation causes patients to be extremely vulnerable to normally mild childhood illnesses such as rotavirus and enterovirus. Prof. Liston’s comprehensive analysis of the genetic defect allows clinicians to provide children with the proper therapies before illnesses prove fatal. The findings of the research have been published in the Journal of Allergy and Clinical Immunology.

Recent advancements in technologies and tools now make it possible for researchers to identify extremely subtle defects of the human immune system. In the past, many patients with “hidden” immunodeficiencies, or defects that were not obvious from the outset, often become extremely ill or die before their genetic disorders are diagnosed. Prof. Liston and his lab were able to identify a gene mutation causing an immunodeficiency that can be fatal during childhood, enabling children to be diagnosed, monitored and preemptively treated for the disorder.

Immunodeficiency disorders are not rare

Ranging from disorders as severe as the well-known “bubble boy” to nearly impossible-to-detect ‘hidden’ defects, immunodeficiencies are more common than scientists previously thought. Immunologists and geneticists have only just begun to scratch the surface when it comes to defining these latter types of immune disorders, which can be specific enough to make sufferers highly susceptible to just one or two types of diseases.

Prof. Adrian Liston (VIB-KU Leuven): “I wouldn’t be surprised if, when we finally do complete the identification of all genetic immunodeficiencies, we discover that up to 1 in 100 children are affected. The ‘hidden’ ones are especially insidious, because they do not present as obviously as other genetic immune disorders. In our study, one of the patients did unfortunately die before a diagnosis could be made. The other patient is alive and well, and now that she has been diagnosed, she is being carefully watched. We can do something about most immunodeficiencies – if only we can identify them.”

Severe common illnesses may signal immune disorder

Prof. Meyts, lead clinician for the patients, stresses the importance of assessing the severity of childhood illnesses on the part of parents, suggesting that parents look for helpful information online and raise the possibility of a potential genetic immunodeficiency with a pediatrician.

Prof. Isabelle Meyts (UZ Leuven – KU Leuven): "When an otherwise healthy child experiences extremely severe infection with a common pathogen, like influenza or the chickenpox virus, or whenever a child is particularly vulnerable to infection with a single pathogen, an underlying defect in the immune system is likely. Likewise, a family history of a child succumbing to infection should alert the family and the clinician. Identifying the causative gene defect allows for genetic counseling of the family and for preventive measures to be taken."

Unraveling ‘hidden’ immunodeficiencies

The potential future avenues for this research are numerous and extremely relevant to current medicine. Prof. Liston’s lab has developed a unique immune phenotyping platform and gene discovery program that can help identify previously unknown immune system defects and inflammatory diseases, leading to novel new treatments that can be administered in a timely way.

Prof. Adrian Liston: “We seek to identify every possible cause of genetic immunodeficiency so that every child displaying warning signs can be tested and treated before it is too late.”

Effecting change as an animal rights advocate

I have been an animal rights advocate for my entire adult life. I am also a medical researcher, specialising in the translation of advances from mouse immunology to patients. I am a vegetarian, for ethical reasons, and yet I am director of the mouse genetic engineering service at KUL. How can one be an advocate for both animal rights and for the use of animals in medical research?

Few would argue against medical research. Who wants a life that is nasty, brutish and short? When I first entered medical research I considered starting in a research project that did not use animals, so that my dual passions did not come into conflict. In the end, however, I decided to work on a mouse model of Multiple Sclerosis – scenes of which would certainly be confronting if shown to the public out of context. I did so because I could not bear to be a hypocrite, willing to take advantage of the outcomes of laboratory animal use, but not willing to get my own hands dirty. Since then, advances in Multiple Sclerosis research in mice have resulted in better treatments for patients, with new medications capable of adding decades of healthy life to the millions of sufferers. Who would be willing to deny their loved ones access to these medicines, despite the work being based on animal models?

At the same time, few would argue against animals having rights. We no longer throw cats from the belfry in Ypres, or other such wanton brutality that was once commonplace. Cruelty against pets is now criminal and farms are inspected for the treatment of livestock. The most intensive protections for animals are reserved for animals in medical research. In order to even start research on mice I have taken countless training courses and filled in hundreds of pages of animal health assessments. My mice are kept in conditions that would be luxurious for wild mice, and have daily health checks by trained staff. The use of each individual mouse is assessed by an external ethics panel, including an ethicist and a veterinary surgeon. I assure you that nothing as brutal as a mouse trap or rat poison would pass muster, let alone the conditions that wild mice endure daily!

Animal research is the bedrock of medical research. Even as we continue to refine, reduce and replace animals in research, we need to accept that all of our advances rest upon work done in animals. At the same time, and rightfully so, laboratory animals have the strongest legal and ethical protections of any animals in our society.

This is not to say that animal use in medical research cannot be improved. Not all researchers have a full awareness of the responsibility that comes with animal research, and violations of animal rights do occur. But the worst thing that we can do would be to reverse progress with a knee-jerk reaction. Attempts to reduce animal research by increasing bureaucratic burden simply de-emphasize the most important regulations. An extra tax on animal use in medical research will need to be paid by reducing the number of trained staff caring for the animals. Public condemnation of animal researchers in the media shuts down dialog. We need to increase, not decrease, communication between animal rights advocates and medical research advocates. Animal rights groups that demand absolutes only make progress more difficult for moderates. Those of us willing to proceed with mutual respect know that the only way to continue the steady improvements in laboratory animal conditions is to increase openness and transparency. If you are an animal rights advocate that actually wants to effect change, I encourage you to work with, instead of against, medical researchers. We will listen. 

Hoe kan iemand tegelijk opkomen voor dierenrechten als voor het gebruik van proefdieren?

Knack:

'Het ergste wat we kunnen doen is om in een paniekreactie alle vooruitgang te blokkeren', schrijft professor Adrian Liston (KU Leuven en VIB). Hij roept de dierenreachtenactivisten daarom op om de dialoog aan te gaan.

Al heel mijn volwassen leven zet ik me in voor dierenrechten en dierenwelzijn. Ik ben ook een medisch onderzoeker, gespecialiseerd in het vertalen van nieuwe immunologische inzichten van muizen naar patiënten. Ik ben vegetariër, om ethische redenen, en toch sta ik aan het hoofd van de dienst voor genetische manipulatie van muizen aan de KU Leuven. Hoe kan iemand opkomen zowel voor de rechten van dieren als voor het gebruik van dieren in medisch onderzoek?

Bijna niemand is tegen medisch onderzoek. Wie wil er nu een hard en kort leven? Toen ik voor het eerst als onderzoeker aan de slag ging overwoog ik een project waarbij geen proefdieren werden gebruikt, zodat mijn twee overtuigingen niet met elkaar in conflict kwamen. Uiteindelijk heb ik toch besloten om te werken op een muismodel van Multiple Sclerose of MS - proeven die zeker confronterend zouden overkomen als ze uit hun context aan het publiek getoond zouden worden.

De reden voor mijn besluit was dat ik niet schijnheilig kon blijven, enerzijds bereid om mee te profiteren van de resultaten van proefdieronderzoek, maar niet om mijn eigen handen vuil te maken. Sindsdien is er heel wat vooruitgang geboekt in het MS-onderzoek. Dankzij dierproeven zijn er nu betere behandelingen en nieuwe geneesmiddelen die miljoenen patiënten heel wat extra gezonde jaren opleveren. Wie wil hun vrienden of familie deze geneesmiddelen ontzeggen, zelfs al is het werk gebaseerd op dierlijke modellen?

Uitgebreide regelgeving voor proefdieren

Tegelijkertijd is zo goed als iedereen het er over eens dat ook dieren rechten hebben. We gooien geen katten meer van het belfort in Ieper, of andere van die brutaliteiten die onder het mom van traditie jarenlang gebeurden. Dierenmishandeling is nu gelukkig strafbaar en de behandeling en huisvesting van vee op boerderijen wordt nauwlettend geïnspecteerd. De meest uitgebreide regelgeving op het vlak van dierenbescherming is weggelegd voor proefdieren in medisch onderzoek. Vooraleer zelfs maar te mogen starten met muizenonderzoek heb ik talloze opleidingen gevolgd en honderden pagina's medische keuringen en ethische dossiers ingevuld.

In vergelijking met wilde muizen, leven mijn muizen in luxueuze omstandigheden, en hun gezondheid wordt dagelijks gecontroleerd door opgeleid personeel. Het gebruik van elke individuele muis wordt beoordeeld door een externe ethische commissie, met inbegrip van een ethicus en een dierenarts. Ik kan u verzekeren dat niets zo brutaal als een muizenval of rattengif die commissie zou passeren, laat staan alle andere ongemakken die wilde muizen dagelijks te verduren krijgen.

Dierproeven vormen de basis van medisch onderzoek. Zelfs wanneer we doorgaan met het verfijnen, verminderen en vervangen van dierproeven moeten we accepteren dat al onze nieuwe wetenschappelijke inzichten berusten op werk verricht bij dieren. Tegelijkertijd hebben proefdieren de sterkste wettelijke en ethische bescherming van alle dieren in onze samenleving, en terecht ook.

Dit wil niet zeggen dat het gebruik van proefdieren in medisch onderzoek niet verder kan worden verbeterd. Niet alle onderzoekers zijn zich volledig bewust van de verantwoordelijkheden die dierproeven met zich meebrengen, en schendingen van de rechten van dieren komen helaas voor. Maar het ergste wat we kunnen doen is om in een paniekreactie alle vooruitgang te blokkeren. Pogingen om dierproeven te verminderen door het verhogen van de bureaucratische lasten zorgen er gewoon voor dat er minder aandacht geschonken wordt aan de belangrijkste regels. Een extra belasting op dierproeven in medisch onderzoek zal worden betaald door het verminderen van het aantal opgeleide medewerkers die zorgen voor de dieren.

Onderzoekers publiekelijk veroordelen in de media sluit de deur voor iedere dialoog. We moeten zorgen voor meer, niet minder, communicatie tussen voorstanders van dierenrechten en van medisch onderzoek. Dierenrechtengroeperingen met absolute eisen maken vooruitgang enkel moeilijker voor gematigden. Diegenen onder ons die bereid zijn om door te zetten met wederzijds respect weten dat meer openheid en transparantie de enige manier zijn om de levensomstandigheden van proefdieren te verbeteren. Als u een dierenrechtenactivist bent die echt verandering teweeg wilt brengen, dan moedig ik u aan om mee te werken met medische onderzoekers, in plaats van tegen ons. Bij ons vindt u alvast een luisterend oor.

Adrian Liston is professor aan de KU Leuven en VIB. Hij staat aan het hoofd van de afdeling genetische manipulatie op muizen.