PMID- 8975900
OWN - NLM
STAT- MEDLINE
DCOM- 19970203
LR  - 20210526
IS  - 0019-9567 (Print)
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Linking)
VI  - 65
IP  - 1
DP  - 1997 Jan
TI  - Immunoglobulin E, a pathogenic factor in Plasmodium falciparum malaria.
PG  - 116-21
AB  - Most children and adults living in areas where the endemicity of Plasmodium 
      falciparum malaria is high have significantly elevated levels of both total 
      immunoglobulin E (IgE) and IgE antimalarial antibodies in blood. This elevation 
      is highest in patients with cerebral malaria, suggesting a pathogenic role for 
      this immunoglobulin isotype. In this study, we show that IgE elevation may also 
      be seen in severe malaria without cerebral involvement and parallels an elevation 
      of tumor necrosis factor alpha (TNF). IgE-containing serum from malaria immune 
      donors was added to tissue culture plates coated with rabbit anti-human IgE 
      antibodies or with P. falciparum antigen. IgE-anti-IgE complexes as well as 
      antigen-binding IgE antibodies induced TNF release from peripheral blood 
      mononuclear cells (PBMC). Nonmalaria control sera with no IgE elevation induced 
      significantly less of this cytokine, and the TNF-inducing capacity of malaria 
      sera was also strongly reduced by passing them over anti-IgE Sepharose columns. 
      The cells giving rise to TNF were adherent PBMC. The release of this cytokine 
      probably reflects cross-linking of their low-affinity receptors for IgE (CD23) by 
      IgE-containing immune complexes known to give rise to monocyte activation via the 
      NO transduction pathway. In line with this, adherent monocytic cells exposed to 
      IgE complexes displayed increased expression of CD23. As the malaria sera 
      contained IgG anti-IgE antibodies, such complexes probably also play a role in 
      the induction of TNF in vivo. Overproduction of TNF is considered a major 
      pathogenic mechanism responsible for fever and tissue lesions in P. falciparum 
      malaria. This overproduction is generally assumed to reflect a direct stimulation 
      of effector cells by certain parasite-derived toxins. Our results suggest that 
      IgE elevation constitutes yet another important mechanism involved in excessive 
      TNF induction in this disease.
FAU - Perlmann, P
AU  - Perlmann P
AD  - Department of Immunology, Stockholm University, Sweden. peter.perlmann@imm2.su.se
FAU - Perlmann, H
AU  - Perlmann H
FAU - Flyg, B W
AU  - Flyg BW
FAU - Hagstedt, M
AU  - Hagstedt M
FAU - Elghazali, G
AU  - Elghazali G
FAU - Worku, S
AU  - Worku S
FAU - Fernandez, V
AU  - Fernandez V
FAU - Rutta, A S
AU  - Rutta AS
FAU - Troye-Blomberg, M
AU  - Troye-Blomberg M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Antibodies, Protozoan)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, IgE)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Adult
MH  - Africa
MH  - Antibodies, Protozoan/blood
MH  - Child
MH  - Humans
MH  - Immunoglobulin E/*blood
MH  - Immunoglobulin G/blood
MH  - Leukocytes, Mononuclear/*metabolism
MH  - Malaria, Cerebral/etiology/immunology
MH  - Malaria, Falciparum/*etiology/immunology
MH  - Receptors, IgE/metabolism
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
PMC - PMC174564
EDAT- 1997/01/01 00:00
MHDA- 1997/01/01 00:01
PMCR- 1997/01/01
CRDT- 1997/01/01 00:00
PHST- 1997/01/01 00:00 [pubmed]
PHST- 1997/01/01 00:01 [medline]
PHST- 1997/01/01 00:00 [entrez]
PHST- 1997/01/01 00:00 [pmc-release]
AID - 10.1128/iai.65.1.116-121.1997 [doi]
PST - ppublish
SO  - Infect Immun. 1997 Jan;65(1):116-21. doi: 10.1128/iai.65.1.116-121.1997.