!!Jos van der Meer - Achievements and anecdotes
!Syndrome HIDS

In 1984, I published the first paper on hyper-immunoglobulinemia D and periodic fever, a new syndrome.  This was the start of my research  on interleukin-1 (IL-1) and my collaboration with Dr Charles A Dinarello, since I felt that this fever syndrome might be an IL-1 disease. At that time, it was impossible to demonstrate. In the early 1990’s Joost Drenth and I collected data on the patients in the Netherlands and abroad and characterised the inflammatory response in this syndrome. Indeed there seemed to be an increased IL-1ß production of the white blood cells. At one of the Workshops on the syndrome we organised we decided to call the syndrome HIDS. In 1999, we could establish – together with Dr Marc Delpech in Paris – that the syndrome was due to mutations of the gene coding for mevalonate kinase, an enzyme in the cholesterol synthesis pathway. Independently – and at the same time – the group of Professor Ronald Wanders (Amsterdam), also found this genetic defect.
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Anna Simon, Joost Drenth and I further established that HIDS should be considered an auto-inflammatory syndrome. Some 5 years ago, we and others discovered that recombinant interleukin-1 receptor antagonist (IL-1RA, anakinra) is an effective treatment for HIDS. This finding not only provides patients with an effective treatment, but also provides further proof that HIDS is an interleukin-1 disease.
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!The role of cytokines in health and inflammatory disease
Since 1987, I worked on the role of cytokines in health and inflammatory disease. The work started in Boston was continued in Nijmegen. In 1992 Bart-Jan Kullberg joined my group and in 1994 Mihai Netea and in 2007 Leo Joosten joined. Major findings of the group are:
*Interleukin-1 (IL-1) stimulates host defense against infection through interference with lethal cytokinaemia
*Hyperlipoproteinaemia defends the host against Gram-negative bacterial infection, but not against fungal infection.
*Toll-like receptor 2 stimulation predisposes for IL-10 production and induction of T regulatory lymphocytes
*Bartonella lipopolysaccharide is a non-toxic, complete blocker of Toll-like receptor 4 (TLR4)
*The fungal pathogen Candida albicans exhibits a series of molecular patterns that are recognised by different pattern recognition receptors.
*The macrophage mannose receptor strongly induces IL-17 in response to Candida albicans
*The processing of IL-1beta is not exclusively dependent on caspase-1; enzymes like PR3 are also important in vivo.
*Contrary to the current dogma, it is clear that caspase-1 is readily present in monocytes and exsudate macrophages
*During the migration of humans out of Africa, evolutionary pressure (probably extered by prevalent infections) has led to profound changes in the occurrence of TLR4 polymorphisms
*Deficiency of dectin-1 leads to increased susceptibility to mucocutaneous fungal infection 
*Reactive Oxygen species enhance the production of IL-1beta.
!Chronic fatigue syndrome (CFS)
Confronted with patients with chronic fatigue syndrome (CFS), I was intrigued by their suffering. Since 1989 together with Gijs Bleijenberg and Jochem Galama, I have performed research trying to understand CFS. Major findings are:
*There is no evidence for a role of persistent infection (such as enteroviral infection, Epstein Barr virus infection, and as most recently established  XMRV infection)
*There are important perpetuating psychological factors, which can be addressed with cognitive behaviour therapy 
*Successful CBT means recovery
*CFS seems to be a central disorder of bodily perception
*Fluoxetine, nutritional supplements, Acclydine and Ondansetron are not effective in CFS (based on our RCTs)
*There is a loss of grey matter in the brain of CFS patients and this is at least partially reversible with successful CBT.
!Antimicrobial resistance
Concerned about the increasing antimicrobial resistance in the world, I was one of the founders (and first chairman) of the Dutch working group on antibiotic policy, SWAB, which receives long-term support from the Ministry of Health in the Netherlands. At the European level, I was a co-founder and first chairman of the ESGAP (ESMID study group on antimicrobial policy).



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