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.

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.

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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