Neuropsychiatric systemic lupus erythematosus (NPSLE) is a rheumatologic disorder causing neurologic, psychiatric and/or psychologic symptoms. The most important clinical problems are the aspecific... Show moreNeuropsychiatric systemic lupus erythematosus (NPSLE) is a rheumatologic disorder causing neurologic, psychiatric and/or psychologic symptoms. The most important clinical problems are the aspecific nature of signs and symptoms, the limited knowledge on pathogenesis and the absence of a diagnostic gold standard. Magnetic resonance imaging (MRI) is considered the most important imaging modality of the brain in NPSLE patients. Abnormalities visible on conventional MRI appear anywhere in the brain, and may normalize, stabilize or increase with loss of brain parenchyma. Apart from conventional MRI sequences, in this thesis advanced MRI techniques such as magnetization transfer imaging (MTI) were also applied, which are more sensitive to microscopic brain damage invisible to the human eye. Microscopic brain damage in NPSLE appears mostly in the cortical gray matter and is associated with the presence of anticardiolipin antibodies. The final brain damage, as observed using different MRI techniques, consists of neuronal and axonal damage, atrophy, demyelination and gliosis. Changes in the total amount of microscopic brain damage as detected by MTI correlate with changes in clinical status. This thesis contributes to the knowledge on the pathogenesis of NPSLE, and illustrates that advanced and conventional radiological techniques can be helpful in making diagnostic and therapeutic decisions. Show less
Diffuse large B cell lymphoma is the most common type of non-Hodgkin lymphoma of which 40% present at extra-nodal sites including immune privileged sites such as the testis and the central nervous... Show moreDiffuse large B cell lymphoma is the most common type of non-Hodgkin lymphoma of which 40% present at extra-nodal sites including immune privileged sites such as the testis and the central nervous system (CNS). Loss of Human Leucocyte Antigen (HLA) expression has been described in many different tumour types as a mechanism to evade anti-tumour immune responsen. In testicular and CNS lymphomas HLA class I and II expression was very commonly observed in contrast to nodal, stomach and skin lymphomas that expressed HLA in most of the cases. Loss of HLA-DR and DQ expression was often due to homozygous deletions of the corresponding genes. Loss of class I expression was often caused by loss of Beta-2-microglobulin expression and hemizygous deletions. Despite their immune privileged status, the testicular and CNS lymphomas showed high numbers of activated cytotoxic T cells, suggesting that these lymphomas are highly immunogenic. DNA-typing for HLA-DR and DQ polymorphisms in testicular and nodal lymphomas revealed a positive association of testicular lymphomas with HLA-DRB1*12 and a negative association of nodal lymphomas with HLA-DRB1*07. Both testicular and nodal lymphomas showed a positive association with HLA-DRB1*15. No significant relationship was found between the different haplotypes and the occurrence of homozygous deletions in the testicular lymphomas. Show less