Cytokine-Associated Neutrophil Extracellular Traps and Antinuclear Antibodies in Plasmodium Falciparum Infected Children under the Age of Six.

• Other Authors: Baker, Virginia Stephens (authoraut)
• Format: Others
• Language: English; English
• Published: Florida State University
• Subjects: Biochemistry; Biophysics; Molecular biology; Immunology; Communicable diseases
• Online Access: http://purl.flvc.org/fsu/fd/FSU_migr_etd-0986

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. === A Dissertation submitted to the Department of Biological Science in partial fulfillment of the requirements for the degree of Doctor of Philosophy. === Degree Awarded: Spring Semester, 2007. === Date of Defense: April 5, 2007. === Anti-Neutrophil Cytoplasmic Antibodies, Innate Immune Protection, ANA, ANCA, Neutrophil Extracellular Traps, Falciparum Malaria, Vaccine Hyporesponsiveness, Nets, Anti-Nuclear Antibodies, Autoimmunity, Cytokines === Includes bibliographical references. === Thomas Keller, III, Professor Directing Dissertation; Qing-Xiang Sang, Outside Committee Member; Robert H. Reeves, Committee Member; Kenneth H. Roux, Committee Member; Wu-Min Deng, Committee Member.