Type of Document	Dissertation
Author	Baker, Virginia Stephens
Author's Email Address	vsb03@hotmail.com
URN	etd-04062007-201144
Title	Cytokine-Associated Neutrophil Extracellular Traps and Antinuclear Antibodies In Plasmodium falciparum Infected Children Under the Age of Six
Degree	Doctor of Philosophy
Department	Biological Science, Department of
Advisory Committee	Advisor Name Title Thomas Keller, III Committee Chair Kenneth H. Roux Committee Member Qing-Xiang Sang Committee Member Robert H. Reeves Committee Member Wu-Min Deng Committee Member
Keywords	Anti-Neutrophil Cytoplasmic Antibodies Innate Immune Protection ANA ANCA Neutrophil Extracellular Traps Falciparum Malaria Vaccine Hyporesponsiveness Nets Anti-Nuclear Antibodies Autoimmunity Cytokines
Date of Defense	2007-04-05
Availability	unrestricted
Abstract In Plasmodium falciparum-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence, and disease severity remain poorly understood. This investigation relates levels of the pro-inflammatory cytokines IFN-g, IL-2, TNF-a, CRP, and IL-6, and select anti-inflammatory cytokines TGF-b and IL-10 to the formation of neutrophil extracellular nets (NETs), IgG antinuclear antibodies (ANA), and IgG antineutrophil cytoplasmic antibodies (ANCA) in blood collected before and seven days after initiation of Sulfadoxine-Pyrimethamine treatment from 21 Nigerian children under six years old presenting with uncomplicated malaria. The children exhibited a Th2 dominated cytokine profile and left-shifted leukocyte differential. Elevated TNF-a levels correlated with significant NET formation evident in the peripheral blood smears. ANA levels (inclusive of all subsets of ANA) were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment but in only 33% of age-matched control samples collected during the season of low parasite transmission. IgG ANA subset levels to dsDNA were significant in 81% of both the pre- and post treatment samples, whereas ANCA levels were positive in only 14% of both the pre-and post-treatment samples. Our results suggest that an inverse relationship between TGF-b and CRP levels may contribute to homeostasis and that TNF-a-associated NET formation and ANA may induce pathology in falciparum-infected children or activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and ANA to dsDNA as a causative factor in the hyporesponsiveness of CpG olignucleotide-based malaria vaccines is discussed.
Files	Filename       Size       Approximate Download Time (Hours:Minutes:Seconds)     28.8 Modem   56K Modem   ISDN (64 Kb)   ISDN (128 Kb)   Higher-speed Access    BakerVDissertation.pdf 9.53 Mb 00:44:07 00:22:41 00:19:51 00:09:55 00:00:50