title: Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age.
abstract: BACKGROUND
  In Plasmodium falciparum-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults.
  
  
  METHODS
  Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-gamma, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-beta and IL-10, and ANA were determined by immunoassay.
  
  
  RESULTS
  The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels 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. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment.
  
  
  CONCLUSIONS
  The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed.
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, Florida, USA. Bakerv@chipola.edu
authors.forename: Virginia S
authors.initials: VS
authors.lastname: Baker
authors.forename: Godwin E
authors.initials: GE
authors.lastname: Imade
authors.forename: Norman B
authors.initials: NB
authors.lastname: Molta
authors.forename: Pallavi
authors.initials: P
authors.lastname: Tawde
authors.forename: Sunday D
authors.initials: SD
authors.lastname: Pam
authors.forename: Michael O
authors.initials: MO
authors.lastname: Obadofin
authors.forename: Soloman A
authors.initials: SA
authors.lastname: Sagay
authors.forename: Daniel Z
authors.initials: DZ
authors.lastname: Egah
authors.forename: Daniel
authors.initials: D
authors.lastname: Iya
authors.forename: Bangmboye B
authors.initials: BB
authors.lastname: Afolabi
authors.forename: Murray
authors.initials: M
authors.lastname: Baker
authors.forename: Karen
authors.initials: K
authors.lastname: Ford
authors.forename: Robert
authors.initials: R
authors.lastname: Ford
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Roux
authors.forename: Thomas Cs
authors.initials: TC
authors.lastname: Keller
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology*; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007958:Leukocyte Count; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D009549:Nigeria; D010963:Plasmodium falciparum / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000974:Antibodies, Antinuclear; D016207:Cytokines; D007074:Immunoglobulin G