B. burgdorferi has a wide variety of strategies to hide from the host immune system. Complement regulatory binding proteins have been described for almost all complement resistant B. burgdorferi sl... Show moreB. burgdorferi has a wide variety of strategies to hide from the host immune system. Complement regulatory binding proteins have been described for almost all complement resistant B. burgdorferi sl, except for the complement resistant B. bavariensis, one of the species that is known to frequently cause Lyme neuroborreliosis. In chapter 2 it is attempted to identify CRASP-1 proteins in B. bavariensis, formerly known as B. garinii OspA serotype 4. Potential CRASP-1 proteins will be cloned and studied for their ability to interact with host derived fluid phase regulators of complement. The specific role of complement resistance in early effective infection and dissemination of B. burgdorferi sl has not been well investigated. Can complement resistance lead to a better and more effective infection and dissemination? In chapter 3 an in vivo experiment in which the infectivity and dissemination patterns of complement sensitive and complement resistant B. burgdorferi sl in a C3 deficient mouse model is described. After effective transmission from the tick to the host the next challenge in B. burgdorferi infection is rapid and accurate detection of the pathogen. Diagnostics of Lyme disease is often compromised due to specific pathogen properties combined with technical shortcomings of bacterial serology. Two indirect detection methods which can aid in diagnosing patients suffering from Lyme neuroborreliosis were studied. In chapter 4 the performance of the C6-peptide ELISA for detecting antibodies in CSF in Lyme neuroborreliosis patients is studied. While in chapter 5 levels of CXCL13 in several patient populations as a potential biomarker for the diagnosis of Lyme neuroborreliosis is studied. For both indirect markers of presence of B. burgdorferi the specificity in clinically resembling and neuroinfectious diseases is of key importance. Several other infectious and inflammatory diseases that have a clinical presentation that can resemble Lyme disease are included in the analysis. Diagnosing Lyme disease can be difficult in some populations, first because Lyme disease is a relatively rare infection, resembling a large spectrum of other autoimmune and inflammatory diseases. Clinicians could often consider testing for Lyme disease. It is also important to do this in specific preselected populations, because the positive predictive value of a test, but specifically indirect tests such as serology, in a random population, is low.In chapter 6 all patients that present with complaints of arthritis at the early arthritis clinic are tested for Lyme arthritis. The prevalence of B. burgdorferi seropositivity in this population is studied. Another aim is to identify clinical factors which should urge the doctor to test, or explicitely not test, for Lyme disease in a patient presenting with arthritis in Europe. In chapter 7 a case of an HIV positive patient presenting with a meningoencephalitis caused by B. burgdorferi is described. The literature on HIV and Lyme neuroborreliosis co-infections is also reviewed. Show less
Pathology laboratories throughout the world have compiled large archives of unique collections of tissue specimens. These tissue samples are used for patient diagnostics and research. Novel... Show morePathology laboratories throughout the world have compiled large archives of unique collections of tissue specimens. These tissue samples are used for patient diagnostics and research. Novel molecular insights into alterations in normal cellular function have led to the identification of targets for innovative therapies. Testing for biomarkers combined with molecular pathology has created the potential for __personalized medicine__ and improved diagnosis, treatment and prognosis. New technologies for molecular analysis in molecular tumor diagnostics and research must be developed and implemented to keep pace with the latest insights, resulting in a constant cycle of change. Such translational research can only progress if patient material can be accessed from the archives for further study. The resulting new insights and strategies will eventually be implemented in patient care. This thesis describes three important issues in this cycle of change with a focus on molecular pathology. Tissue preparation, method development and data analysis. Show less
