Biomarkers measured in the blood can provide information about disease pathophysiology, diagnosis and prognosis. Pronounced proinflammatory responses are characteristic of severe malaria, and excessive activation of the immune system is central to the pathophysiology of both cerebral malaria and placental malaria. Severe malaria is characterized by cytoadherence of parasitized erythrocytes to the microvasculature; impaired tissue perfusion; dysregulated inflammatory responses; and activation of the complement system, mononuclear cells, and endothelium. Despite the availability of effective antimalarial drugs, the mortality rate in severe malaria remains unacceptably high. To glean further insight into malaria pathophysiology, we investigated host biomarkers of immune activation in the blood of subjects with different manifestations of severe disease. C5 has been identified as being necessary and sufficient for the development of experimental cerebral malaria. We hypothesized that C5a (a terminal component of the complement cascade with potent inflammatory properties) may mediate its action by inducing and exacerbating inflammatory processes in severe malaria, leading to endothelial activation and dysregulated angiogenesis. I tested this hypothesis in vitro, and found that C5a interacted with malaria toxin PfGPI to drive deleterious inflammatory and anti-angiogenic responses. As C5a and anti-angiogenic factor sFlt-1 have been implicated in models of pathologic pregnancies, we asked whether increased levels of C5a in subjects with placental malaria were associated with altered angiogenesis and poor birth outcomes. Our results suggest that C5a impairs angiogenic remodelling in placental malaria leading to vascular insufficiency and fetal growth restriction. Further, altered profiles of inflammatory and angiogenic biomarkers in the periphery may identify occult placental malaria infections. We extended these observations to cerebral malaria where similar pathogenic pathways contribute to disease pathophysiology. In adults and children with cerebral malaria, altered profiles of angiogenic proteins were associated with disease severity and mortality and represent putative diagnostic and prognostic biomarkers in severe malaria.

Biomarkers measured in the blood can provide information about disease pathophysiology, diagnosis and prognosis. Pronounced proinflammatory responses are characteristic of severe malaria, and excessive activation of the immune system is central to the pathophysiology of both cerebral malaria and placental malaria. Severe malaria is characterized by cytoadherence of parasitized erythrocytes to the microvasculature; impaired tissue perfusion; dysregulated inflammatory responses; and activation of the complement system, mononuclear cells, and endothelium. Despite the availability of effective antimalarial drugs, the mortality rate in severe malaria remains unacceptably high. To glean further insight into malaria pathophysiology, we investigated host biomarkers of immune activation in the blood of subjects with different manifestations of severe disease. C5 has been identified as being necessary and sufficient for the development of experimental cerebral malaria. We hypothesized that C5a (a terminal component of the complement cascade with potent inflammatory properties) may mediate its action by inducing and exacerbating inflammatory processes in severe malaria, leading to endothelial activation and dysregulated angiogenesis. I tested this hypothesis in vitro, and found that C5a interacted with malaria toxin PfGPI to drive deleterious inflammatory and anti-angiogenic responses. As C5a and anti-angiogenic factor sFlt-1 have been implicated in models of pathologic pregnancies, we asked whether increased levels of C5a in subjects with placental malaria were associated with altered angiogenesis and poor birth outcomes. Our results suggest that C5a impairs angiogenic remodelling in placental malaria leading to vascular insufficiency and fetal growth restriction. Further, altered profiles of inflammatory and angiogenic biomarkers in the periphery may identify occult placental malaria infections. We extended these observations to cerebral malaria where similar pathogenic pathways contribute to disease pathophysiology. In adults and children with cerebral malaria, altered profiles of angiogenic proteins were associated with disease severity and mortality and represent putative diagnostic and prognostic biomarkers in severe malaria.

Thesis (Ph. D.)--Virginia Commonwealth University, 2007. / Prepared for: Dept. of Microbiology and Immunology. Bibliography: leaves 127-137. Available online via the Internet.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Thesis (Ph.D. (Biochemistry))--Mahidol University, 1984.

Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xviii, 212 p.; also includes graphics (some col.) Includes bibliographical references (p. 185-212). Available online via OhioLINK's ETD Center

Thesis (Ph. D.)--Case Western Reserve University, 2005. / [School of Medicine] Department of Biochemistry. Includes bibliographical references. Available online via OhioLINK's ETD Center.

No description available.

Sensitivity of spirochetes from Borrelia burgdorferi sensu lato complex to serum complement of humans of different age and sex was analyzed. Complement-mediated Borrelia killing was observed in different combination of serum and selected Borrelia genospecies. The obtained results confirmed that age itself does not influence the sensitivity of human to Borrelia infection. However, the females seem to be more vulnerable to it. Each of ten tested Borrelia species was proved to be potentially infective for human in different ratio. The clear separation of all ten checked Borrelia species into two groups was revealed after the reaction with human sera: species with low sensitivity to human serum complement (mortality below 1 percent) and species with higher sensitivity (mortality over 3-4 percent).

The diagnosis of antibody-mediated rejection after liver transplantation is complicated, due to the fact that the clinical and pathological signs of this life- threatening complication are often overlapping with non-immunological symptoms, like biliary obstruction, ischemia, thrombosis and others. Furthermore, the transplanted liver is to a great extent resistant to this type of rejection. Like in the transplanted kidney and heart, the main pathological factors of graft injury are antibodies directed to the mismatched HLA antigens of the organ donor, i.e. donor- specific antibodies. Besides analysis of HLA specificity of antibodies, research lately has been directed to define whether these antibodies are complement-binding or not. Literature data on this are however up till now limited. Therefore, the aim of this diploma thesis was to study the clinical relevance of complement-binding antibodies against HLA antigens in patients after liver transplantation. Our preliminary results suggest that there might be a correlation between the presence of complement-binding antibodies and the development of antibody-mediated rejection. This finding may play a role for improvement of the prognosis of patients after liver transplantation. Key words HLA, antibodies, C4d, complement, liver transplantation