In this thesis several aspects of SLE were investigated. First, we studied interobserver agreement concerning class III/IV lupus nephritis lesions in a renal biopsy and found that agreement was... Show moreIn this thesis several aspects of SLE were investigated. First, we studied interobserver agreement concerning class III/IV lupus nephritis lesions in a renal biopsy and found that agreement was poor. This seemed, in part, due to inconsistent or ambiguous definitions as provided in the 2004 ISN/RPS classification. This led us to re-evaluate the current classification with an international group of highly experienced nephrologists. Second, we compared and summarized the lupus nephritis management guidelines that were published in 2012. Third, we studied microchimerism in peripheral blood of women with SLE and control subjects. We found that women with SLE have more microchimerism in their peripheral blood than control subjects. Then, we studied microchimerism in the peripheral blood of women with SLE and control subjects during and after pregnancy. We found that only just after delivery did the SLE patients have more chimeric cells in the granulocyte fraction than control subjects. These results suggest that after pregnancy chimeric cells become undetectable in peripheral blood, but possibly remain at other sites, only to re-emerge after un unknown trigger. Finally, we compared sporadic and familial lupus nephritis to find that, although there were clinical differences, no differences in histology or genetic background were apparent. Show less
This thesis emphasizes the presence of minor H antigen specific immune responses directly after birth, which will be present throughout life. The presence of minor H antigen mismatched... Show moreThis thesis emphasizes the presence of minor H antigen specific immune responses directly after birth, which will be present throughout life. The presence of minor H antigen mismatched microchimeric cells obtained through pregnancy from a mother or a child play a crucial role in this. Subsequent immunization against minor H antigens can lead to both cytotoxic and tolerogenic responses. Furthermore HA-1 specific T cells can share the same TCR Vbeta, yet being functionally different. The here performed studies enhances our understanding of immune reactions after HSCT and if applicable after renal transplantation, especially regarding the birth order effect and the assumed less favourable role of women as transplant donors. Show less
In this thesis we focused on microscopic and flow cytometric methods suitable to quantify fetal red cells in maternal blood. We compared several methods for FMH quantification both in spiked... Show moreIn this thesis we focused on microscopic and flow cytometric methods suitable to quantify fetal red cells in maternal blood. We compared several methods for FMH quantification both in spiked samples and samples from pregnant women following invasive procedures and complications in pregnancy. We developed a technique for automated read-out of Kleihauer-Betke stained slides to enumerate fetal red cells in maternal blood. We studied the biological behaviour of fetal red and mononuclear cells (MNCs) in the maternal circulation after large FMH and the rate by which these cells are cleared from the maternal circulation. We identified fetal MNCs using a staining with a monoclonal antibody (mAb) directed against the paternally inherited HLA-A2. Furthermore, we discuss the importance of a correct use of the formula to calculate the FMH volume. Show less
