Immunoglobulin E, a pathogenic factor in Plasmodium falciparum malaria

Abstract

Proteins that are actively secreted by Mycobacterium tuberculosis generate immune responses in the infected host. This has prompted the characterization of protein components of mycobacterial culture filtrates to develop subunit vaccines and immunodiagnostic reagents. Fractionation of filtrates of M. tuberculosis cultures has yielded an abundant protein called MPT63, which has an apparent molecular mass of 18 kDa. We report the molecular cloning and nucleotide sequence of the mpt63 gene, purification of recombinant MPT63 antigen from Escherichia coli cells, and serological characterization of MPT63. Nucleotide sequence analysis of mpt63 identified an open reading frame encoding a protein of 159 amino acids (aa) consisting of a 29-aa secretion signal peptide and a 130-aa mature MPT63 protein. Recombinant MPT63 protein, purified from E. coli cells, and native MPT63, purified from M. tuberculosis culture filtrates, were indistinguishable in serological assays. Thus, the recombinant protein constitutes a valuable reagent for immunological studies. MPT63 evoked humoral immune responses in guinea pigs infected with virulent M. tuberculosis by the aerosol route. The mpt63 gene is found only in species of the M. tuberculosis complex, as shown by DNA hybridization experiments. Moreover, polyclonal antibody against MPT63 does not cross-react with proteins of a common environmental mycobacterial species, Mycobacterium avium. The absence of cross-reactive epitopes makes MPT63 an attractive candidate as an M. tuberculosis complex-specific diagnostic reagent. In particular, evaluation of MPT63 as an M. tuberculosis complex-specific reagent for diagnostic skin testing is under way.

The Role of Serum Immunoglobulin E in the Pathogenesis of Plasmodium falciparum Malaria in Ivorian Children

“…On the contrary, our results confirm those of several other authors [5][6][7][8][9] who observed higher IgE serum levels during the course of P. falciparum malaria. We could attribute this rise of the IgE serum level to a protector role during malarial infection, as Helmby and Perlmann [10,11] also reported. In addition, the IgE level was increased in older subjects.…”

“…Yet, it had been proved that the pro-inflammatory TNF-a and septic shock cytokine are among the factors responsible for the induction of cerebral injuries in the course of severe malaria. Perlmann et al [11] also have reported this destructive role of the IgE in P. falciparum malaria.…”

Increased eosinophil activity in acutePlasmodium falciparuminfection—association with cerebral malaria

“…Although we could not demonstrate a correlation between IgE levels and eosinophil granule proteins, it should be noted that high levels of IgE have been demonstrated in CM [21]. In this case it was suggested that IgE complexes could contribute to cerebral symptoms via TNF induction [22]. Further studies are needed to elucidate the interplay between eosinophils, IgE and TNF in the pathogenesis of CM.…”

Critical role of the neutrophil-associated high-affinity receptor for IgE in the pathogenesis of experimental cerebral malaria

“…In humans, studies aiming at establishing the allergic nature of malaria disease report conflicting results ranging from disease-aggravating to disease-protecting roles of IgE (Perlmann et al, 1997; Bereczky et al, 2004). To clarify this issue, we used genetically deficient animals or antibody-depleted cell populations to examine crucial components of the allergic inflammatory response in malaria pathogenesis.…”