In this thesis, the involvement of the complement system was studied in various diseases that affect the microvasculature of the kidney. We focused on the clinicopathologic significance of... Show moreIn this thesis, the involvement of the complement system was studied in various diseases that affect the microvasculature of the kidney. We focused on the clinicopathologic significance of complement deposits along the renal microvasculature of patients with thrombotic microangiopathy, a disorder that is characterized by severe endothelial injury and microvascular thrombosis; IgA nephropathy and IgA vasculitis with nephritis, auto-immune disorders that can cause microvascular injury in adults and children; transplant glomerulopathy, an important cause of late graft dysfunction and renal allograft loss; preeclampsia, a leading cause of maternal and perinatal morbidity and mortality; and diabetic nephropathy, a microvascular complication of diabetes mellitus and a leading cause of end-stage renal disease. Special attention was paid to C4d, a cleavage product of C4 activation, which is commonly used as a biomarker for complement activation. Our data suggest that the complement system is involved in the pathogenesis of various renal microangiopathies and that complement activation along the microvasculature may contribute to disease progression in a subset of patients. Our findings may contribute to the development of improved diagnostic workup, new therapeutic strategies and patient-tailored therapy. Show less
In this thesis we have analyzed an important number of laboratory, radiological, clinical and patient´s reported outcomes in systemic lupus erythematosus (SLE) patients presenting with... Show moreIn this thesis we have analyzed an important number of laboratory, radiological, clinical and patient´s reported outcomes in systemic lupus erythematosus (SLE) patients presenting with neuropsychiatric (NP) manifestations. Our studies are among the most robust to date in this field due to the large number of patients included, the prospective character and the standard assessment followed by a multidisciplinary expert consensus.Furthermore our studies include the novelty of a phenotypic characterization of all NP manifestations according to the suspected underlying pathophysiological mechanism (inflammation or immune-mediated vs. ischemic or thrombotic). These studies give more light to the understanding of the underlying pathophysiological mechanisms of nervous involvement in SLE. Show less
