New disease (and cure!) found

As part of an ERC funded research program, the Autoimmune Genetics Laboratory is searching the genomes of young children with severe immune diseases to look for novel genes (and hopefully treatments). In a collaboration with Prof Carine Wouters and Prof Isabelle Meyts at UZ Leuven, we found mutations in a new gene, CECR1, in three severely ill children. Two of the children were born with a severe immune deficiency, making them prone to infections, while the third developed an inflammatory disease known as Castleman's disease. Mutations in the same gene, which produces the protein ADA2, were independently found by two other groups to give vascular disease and early-onset stroke. 

These studies identify ADA2-deficiency as a previously undiagnosed primary immunodeficiency which includes components of immune deficiency, inflammation and vasculopathy. Most importantly, this new diagnosis comes with a successful cure: prior to genetic diagnosis, our clinical collaborators were able to successfully treat the disease with bone-marrow transplanation (for the immunodeficient patient) or tocilizumab (for the Castleman's disease patient). These results therefore not only add to our knowledge about medical genetics, but also provide a direct diagnosis-treatment pathway for any new children identified with these severe diseases.

Read more:

Van Eyck, Hershfield, Pombal, Kelly, Ganson, Moens, Frans, Schaballie, De Hertogh, Dooley, Bossuyt, Wouters, Liston* and Meyts*. Hematopoietic stem cell transplantation rescues the immunologic phenotype and prevents vasculopathy in patients with adenosine deaminase 2 deficiency. J Allergy Clin Immunol. 2015 Jan;135(1):283-287.e5.

Van Eyck, Liston and Wouters. Mutant ADA2 in vasculopathies. N Engl J Med. 2014 Jul 31;371(5):480

Van Eyck, Liston and Meyts. Mutant ADA2 in vasculopathies. N Engl J Med.  2014 Jul 31;371(5):478-9.

If you would like to support our clinical research, and allow us to take on more cases like this one, 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".

A new look at immune ageing

The thymus is the organ in which all T cells, a key white blood cell in our immune system, develop. The thymus shrinks with age, degenerating from a plump milky organ (just above the heart) to a ratty-looking fat-riddled vestige which barely produces any new T cells. This degeneration means that older persons are producing fewer and fewer T cells, contributing to the poor responses to vaccines and infections with age. Despite the importance of this process, there is a great debate in immunology over why the thymus gets worse with age, with some scientists pointing out the structural degeneration of the thymus itself, while others suggest that it is instead due to poorer function of the bone-marrow that sends stem cells to the thymus to be turned into T cells.

In a new study from the Autoimmune Genetics Laboratory, published in the European Journal of Immunology, we use a range of imaging and genetic techniques to address this key question. We undoubtly find the structural degeneration in the organ with age, but by comparing two mouse strains that have a thymus ageing at different rates, we find that the structural abnormalities do not actually limit production of T cells. Instead, it is the reduced function of the bone-marrow that leads to a reduction in new T cells. These results suggest that researchers looking into immune ageing direct their attention towards the bone-marrow, where rescuing stem cell production may allow even older persons to produce fresh T cells for a healthy life.

Data from Franckaert et al, European Journal of Immunology. The C57BL/6 mouse (top) has a thymus that ages slowly, while the FVB/N mouse (bottom) has a thymus that ages rapidly.

Scientific quote of the day

"To describe an organism, we do not try to specify each molecule in it, and catalogue it bit by bit, but rather to answer certain questions about it which reveal its pattern"

- Norbert Wiener, 1950 (quoted in Intolerant Bodies)

Pathway to a PhD

From my son's colouring-in book:

Relocate your lab to Belgium?

If you've ever thought of relocating your lab to Belgium, there is rarely a better deal than tenure plus up to €7.5 million in funding over five years. The Odysseus grants are opening!

PhD graduation

Congratulations to Dina Danso-Abeam who just graduated from her PhD in the laboratory!

Hints on scientific writing

My advice for writing a scientific article (for a top-tier journal).

Likewise, how to write a cover-letter.

If you get that far - how to interpret the editor's rejection (and you will be rejected) and then how to rebutt it.

Lab retreat

Great science at a very successful annual lab retreat! Special thanks to Michelle Linterman, Sylvie Lesage and An Goris as external evaluators, and our own Wim Cockx for flawless planning.

Jeffrey Modell Foundation supports Belgian research on primary immunodeficiency

For the first time the Jeffrey Modell Foundation is giving a research grant to a Belgian laboratory. The team of Adrian Liston from VIB-KU Leuven will use the grant to develop a gene therapy to cure children that suffer from IPEX syndrome, a rare and fatal autoimmune disorder in which the immune system attacks the body’s own tissues and organs. At the moment, the only successful therapy to treat the syndrome is a bone marrow transplantation, which is not available for all children.

 “This is a real chance for a cure”, said lead-researcher Adrian Liston. “The gene responsible for this disease was identified 13 years ago, but for the first time we may have learned enough about the basic biology to solve it. We should know within a year whether the gene therapy works in mice, after which we can move to patients at top speed.”

The Jeffrey Modell Foundation (JMF)

JMF is a global non-profit organization for patients who suffer from Primary Immunodeficiency (PI) and their relatives. The organization is devoted to early and precise diagnosis, meaningful treatments and, ultimately, cures. Through clinical and basic research, physician education, patient support, advocacy, public awareness and new-born screening they want to make a difference in the lives of patients with PI.

Vicki and Fred Modell established the Foundation in 1987, in memory of their son Jeffrey, who died at the age of fifteen from complications of PI. During the years, the foundation has created a network of the world’s leading expert immunologists. Two years ago the Child Immune Deficiencies Department of UZ Leuven was given the first certification as a "Jeffrey Modell Foundation Diagnostic and Research Center for Primary Immunodeficiencies” in Belgium.

IPEX and primary immunodeficiency (PI)

IPEX is an acronym for immune dysregulation, polyendocrinopathy (diseases affecting multiple endocrine glands), enteropathy (disorder of the intestines), and X-linked (pattern of inheritance).

IPEX Syndrome is classified as a primary immunodeficiency disorder. Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. IPEX is caused by mutations in the FOXP3 gene which lead to the dysfunction of regulatory T cells (a type of white blood cells).

IPEX syndrome is an autoimmune disorder, meaning that the immune system mistakenly attacks the body’s own tissues and organs. The syndrome is characterized by severe diarrhoea, dermatitis (inflammation of the skin), diabetes and severe, life-threatening infections. The disease only affects boys.

Current therapies still remain of partial efficacy. Immunosuppressive drugs are most commonly used, but they only delay the disease. Stem cell transplantation, when performed before severe autoimmunity develops, is currently the only effective cure. However transplantation is only a solution for those children with a compatible donor, unless a gene therapy option is available to correct the mutation in the patient’s own stem cells. 

Update on Wednesday, September 10, 2014 at 3:55PM by Adrian Liston

METRO.be

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Bio-Medicine

Jeffrey Modell Foundation supports Belgian research on primary immunodeficiency

News-medical.net

Belg ontvangt onderzoeksbeurs van Jeffrey Modell om behandelingsIPEX syndroom te helpen

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Amerikaanse beurs voor Vlaams onderzoek naar auto-immunziekte IPEX

BRF.be

Belgische Genforscher erhalten Geld einer US-Stiftung

sNEWSi.com

Jeffrey Modell Foundations supports Belgian research on primary immunodeficiency

LokaalNieuws.be

Amerikaanse beurs voor Vlaams onderzoek naar auto-immunziekte IPEX

Dean Franckaert wins BD Biosciences Research Program award

Congratulations to Dean Franckaert, PhD student in the lab, who won a $10,000 grant from BD Biosciences as part of their sponsored research program!