Alkwin Wanders

Biography

Currently working in Umea University, Sweden

Research Interest

Medical Life Sciences, The significance of enterotropic and neurotope viral infections for the pathogenesis of morbus Crohn, Crohn's disease is an idiopathic disorder characterized by a lifelong chronic recurrent inflammation in the primary digestive tract. What causes Crohn's disease is not known. The disease is considered to be polygen and develops in a complex interaction between environmental factors and aberrant immune response in genetically predisposed individuals. This is supported by the fact that a majority of all genes identified in Crohn's disease, including NOD2 and ATG16L1, have known functions in the immune response to a particular type of virus, a single-stranded RNA virus (ssRNA virus). Loss of the function of the genes leads to a degradation of these ssRNA viruses. This suggests that enteropathogenic viruses can play a role in Crohn's disease. Recently, for the first time - by our own research group - significant incidence of a special ss RNA virus, human enterovirus B (HEV-B), in bowel resections from nine children with advanced Crohn's disease and in mucous membrane biopsy at the initial onset. HEV-B is an ssRNA virus that infects both intestinal epithelium and nervous system. The virus was detected in the intestinal mucosa and in the gangway cells of the enteric nervous system, expressing the cellular receptors of coxsackievirus B (a subspecies of HEV-B). All patients had polymorphisms in NOD2 or ATG16L1. HEV-B occurs in large amounts in the mucous membrane and in the gangway cells of the enteric nervous system. Bowel of control patients with mechanical bowel syndrome contained no or only minimal amounts of virus. Further studies focus on the bowel epithelial barrier. An intact epithelial barrier is important for normal intestinal function. An increased permeability of the digestive epithelium is observed in several autoimmune diseases, including Crohn's disease. Tight junctions (TJ) is a membrane-associated protein complex that controls the permeability of intestinal cells. Several common RNA virus families with tropism for the intestinal mucosa have the ability to interact with TJ proteins, which interfere with their structure and function, with the resultant increase of paracellular permeability. Being own, yet unpublished results from a retrospective study show the occurrence of enteropathogenic viruses (HEV-B) in gastrointestinal biopsies from children in the early onset of CD disease. Studies of TJ proteins in ventricular biopsies showed a loss or downregulation of CAR in cells that had an infection with enterovirus.