Objectives: We aimed to determine the presence, amount and origin of microchimerism in peripheral blood of pregnant and non-pregnant parous women with systemic lupus erythematosus (SLE) as compared... Show moreObjectives: We aimed to determine the presence, amount and origin of microchimerism in peripheral blood of pregnant and non-pregnant parous women with systemic lupus erythematosus (SLE) as compared to control subjects. Methods: We performed a comparative study in which peripheral blood was drawn from eleven female non-pregnant SLE-patients and 22 control subjects, and from six pregnant SLE-patients and eleven control subjects during gestation and up to six months postpartum. Quantitative PCR for insertion-deletion polymorphisms and null alleles was used to detect microchimerism in peripheral blood mononuclear cells and granulocytes. Results: Microchimerism was detected more often in non-pregnant SLE-patients than control subjects (54.4% vs. 13.6%, respectively; p=0.03). When present, the median total number of foetal chimeric cells was 5 gEq/106 in patients and 2.5gEq/106 in control subjects (p=0.048). Microchimerism was mostly foetal in origin; maternal microchimerism was detected in one patient and one control subject. In control subjects, microchimerism was always derived from only one source whereas in 50% of patients it originated from multiple sources. The pregnant patients had a significantly higher median number of foetal chimeric cells in the granulocyte fraction just after delivery than control subjects (7.5 gEq/106 vs. 0 gEq/106, respectively; p=0.02). Conclusions: Just after delivery, SLE-patients had more microchimerism than control subjects. Three months post-partum, microchimerism was no longer detectable, only to reappear many years after the last pregnancy, more often and at higher levels in SLE-patients than in control subjects. This suggests that these chimeric cells may originate from non-circulating foetal chimeric stem cells. Show less
The clinical manifestations and outcomes of systemic lupus erythematosus (SLE) are remarkably heterogeneous. In this thesis, issues relating to the diagnosis and prognosis of SLE were studied,... Show moreThe clinical manifestations and outcomes of systemic lupus erythematosus (SLE) are remarkably heterogeneous. In this thesis, issues relating to the diagnosis and prognosis of SLE were studied, focussing on the application of histopathologic evaluation in conjunction with clinical features in the setting of lupus nephritis (LN) and neuropsychiatric SLE (NP-SLE). In the first part, we demonstrated that classification criteria for SLE cannot be unequivocally applied to patients from nephrology clinics who present with full house glomerular deposits suggestive of LN/SLE. The patients with full house glomerular deposits without clinical SLE represented a distinct entity with a remarkably poor renal outcome. In the second part, clinical and histopathologic determinants of renal outcome were investigated to improve prognostication in LN. First, we identified a subgroup of patients with class III/IV LN with favourable renal outcome indicating that the current classification warrants refinement. Next, we identified prognosticators that may add to the current histopathologic classification of LN. The last part of this thesis was focused on the aetiopathogenesis of SLE, in which the complement system was identified as an important player and thereby therapeutic target in neuropsychiatric lupus and in which pregnancy-acquired microchimerism in relation to the occurrence of SLE was further investigated. Show less
