title: Acquired immune responses to Plasmodium falciparum merozoite surface protein-1 in the human fetus.
abstract: Infants born in areas of stable malaria transmission are relatively protected against severe morbidity and high density Plasmodium falciparum blood-stage infection. This protection may involve prenatal sensitization and immunologic reactivity to malaria surface ligands that participate in invasion of red cells. We examined cord blood T and B cell immunity to P. falciparum merozoite surface protein-1 (MSP-1) in infants born in an area of stable malaria transmission in Kenya. T cell cytokine responses to the C-terminal 19-kDa fragment of MSP-1 (MSP-1(19)) were detected in 24 of 92 (26%) newborns (4-192 IFN-gamma and 3-88 IL-4-secreting cells per 10(6)/cord blood lymphocytes). Peptide epitopes in the N-terminal block 3 region of MSP-1 also drove IFN-gamma and/or IL-13 production. There was no evidence of prenatal T cell sensitization to liver-stage Ag-1. A total of 5 of 86 (6%) newborns had cord blood anti-MSP-1(19) IgM Abs, an Ig isotype that does not cross the placenta and is therefore of fetal origin. The frequency of neonatal B cell sensitization was higher than that indicated by serology alone, as 5 of 27 (18%) cord blood samples contained B cells that produced IgG when stimulated with MSP-1(19) in vitro. Neonatal B cell IgG responses were restricted to the Q-KNG allele of MSP-1(19), the major variant in this endemic area, whereas T cells responded to all four MSP-1(19) alleles evaluated. In utero sensitization to MSP-1 correlated with the presence of malaria parasites in cord blood (chi(2) = 20, p < 0.0001). These data indicate that prenatal sensitization to blood-stage Ags occurs in infants born in malaria endemic areas.
authors.affiliation: Division of Geographic Medicine, Department of Medicine, Case Western Reserve University, Harlan Wood Building, 10900 Euclid Avenue, Cleveland, OH 44106, USA. cxk21@po.cwru.edu
authors.forename: Christopher L
authors.initials: CL
authors.lastname: King
authors.forename: Indu
authors.initials: I
authors.lastname: Malhotra
authors.forename: Alex
authors.initials: A
authors.lastname: Wamachi
authors.forename: John
authors.initials: J
authors.lastname: Kioko
authors.forename: Peter
authors.initials: P
authors.lastname: Mungai
authors.forename: Sherif Abdel
authors.initials: SA
authors.lastname: Wahab
authors.forename: Davy
authors.initials: D
authors.lastname: Koech
authors.forename: Peter
authors.initials: P
authors.lastname: Zimmerman
authors.forename: John
authors.initials: J
authors.lastname: Ouma
authors.forename: James W
authors.initials: JW
authors.lastname: Kazura
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005333:Fetus / Q000276:immunology*; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007074:Immunoglobulin G / Q000096:biosynthesis; D016778:Malaria, Falciparum / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology*; D009154:Mutation; D010455:Peptides / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D007074:Immunoglobulin G; D020066:Merozoite Surface Protein 1; D010455:Peptides; C067302:liver stage-specific antigen, Plasmodium